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Clinical evaluation of the pharmacological impact of ashwagandha root extract on sleep in healthy volunteers and insomnia patients: A double-blind, randomized, parallel-group, placebo-controlled study
Abstract
Ethnopharmacological relevance
Ashwagandha (Withania somnifera (L.) Dunal.) is long known for its sleep-inducing effects. Ashwagandha can be proposed as an alternative to the recommended present treatments for insomnia. This study aimed to evaluate the pharmacological effect of Ashwagandha root extract on sleep in healthy subjects and also in the subjects having insomnia.
Material and methods
We performed a randomized, parallel-group, stratified design, placebo-controlled study. A total of 80 eligible participants, 40 in Arm-A (healthy) and 40 in Arm-B (insomnia) were assigned to two groups, either Ashwagandha or placebo and studied for 8-weeks. The assessment was done based on the sleep parameters (Sleep Onset Latency, Total Sleep Time, Wake After Sleep Onset, Total time in bed, and Sleep Efficiency), Pittsburgh Sleep Quality Index and Hamilton Anxiety scale-A questionnaire, mental alertness on rising assessment, and sleep quality questionnaire. Safety and adverse events along with the concomitant medication were also assessed.
Results
In both healthy and insomnia subjects, there was a significant improvement in the sleep parameters in the Ashwagandha root extract supplemented group. The improvement was found more significant in insomnia subjects than healthy subjects. Repeat measure Analysis of variance (ANOVA) confirmed the significant improvement in SOL (p 0.013), HAM-A outcomes (p < 0.05), mental alertness (p 0.01), and sleep quality (p < 0.05) of the insomnia patients. A two-way ANOVA was used to confirm the outcomes that denoted sleep onset latency (p < 0.0001) and sleep efficiency (p < 0.0001) as the most improved parameters, followed by TST (p < 0.002) and WASO(p < 0.040). All these parameters (SOL, TST, WASO, TIB, SE, PSQI, HAM-A, Mental Alertness, and Sleep quality) were also statistically assessed for the significant improvement within the group both for the treatment, and the placebo groups in the healthy and the insomnia datasets. Obtained results suggest statistically significant (p < 0.0001) changes between the baseline values and the end of the study results except for the HAM-A and the mental alertness scoresn the healthy subject group.
Conclusion
The present study confirms that Ashwagandha root extract can improve sleep quality and can help in managing insomnia. Ashwagandha root extract was well tolerated by all the participants irrespective of their health condition and age. Additional clinical trials are required to generalize the outcome.
... Insomnia and other sleep disorders can have a profound impact on health and quality of life [14]. Common drugs for insomnia can cause side effects such as: nausea, dizziness, daytime fatigue, headache, nightmares and drug dependence [15], thus alternatives such as herbal supplements are being proposed [16]. Rodent study suggested that Ashwagandha can improve sleep duration compared to placebo and decrease sleep latency in caffeine-induced insomnia model. ...
... There was no significant difference in Pittsburgh Sleep Quality Index and total time in bed [18]. Analysed by participant background, those with insomnia demonstrated larger improvements than those without [16,[19][20][21][22]. Positive effect was also more profound with larger doses (≥ 600 mg/d compared to < 600 mg/d) and longer duration (≥ 8 weeks compared to < 8 weeks) [18]. ...
... Positive effect was also more profound with larger doses (≥ 600 mg/d compared to < 600 mg/d) and longer duration (≥ 8 weeks compared to < 8 weeks) [18]. Three studies that examined mental alertness on rising also showed a positive impact of Ashwagandha [16,19,21]. Sleep quality is also shown to be related to stress [23], another target of Ashwagandha supplementation. ...
In recent years Withania somnifera (Ashwagandha) gained a lot of interest as an adaptogen, aiding sleep, stress management and presenting health and sports-related benefits. Although clinical effects have been previously reviewed, the specific mechanism of Ashwagandha’s action and its impact on different aspects of physical performance, body composition, as well as medical effects need more thorough analysis. Therefore, this narrative review delves into the available research examining the effects of Ashwagandha supplementation on such qualities as: strength, endurance, power, recovery, muscle mass, body fat, fertility, anxiety, metabolic health and aging, with additional focus on potential mechanisms underlying these effects. Moreover, we propose future perspectives based on the gaps observed in Ashwagandha research up to date.
... We included five trials with a total of 400 participants [45,[53][54][55][56]. Table 1 further describes the studies included. ...
... Out of the five trials, one trial declared that their study was partially sponsored by the manufacturer [45]. All trials were conducted in India [45,[53][54][55][56]. Three of the trials recruited participants from outpatient clinics [54][55][56], one trial recruited through phone call [45], and one trial did not mention the method of recruitment [53]. ...
... Out of the five trials, one trial declared that their study was partially sponsored by the manufacturer [45]. All trials were conducted in India [45,[53][54][55][56]. Three of the trials recruited participants from outpatient clinics [54][55][56], one trial recruited through phone call [45], and one trial did not mention the method of recruitment [53]. The five trials included in this meta-analysis comprised of two trials with 210 healthy adults [45,53], one trial with 50 healthy elderly over 60 years old [55], one trial with 60 adults diagnosed with insomnia based on DSM-IV [54], and one trial that included two groups of participants which were 40 healthy adults, and 40 adults diagnosed with insomnia based on DSM-IV [56]. ...
Objective
To determine the effect of Ashwagandha extract on sleep.
Methods
A comprehensive search was conducted in CENTRAL, MEDLINE, SCOPUS, Google Scholars, World Health Organization Trials Portal, ClinicalTrials.gov, Clinical Trial Registry of India, and AYUSH Research Portal for all appropriate trials. Randomized controlled trials that examined the effect of Ashwagandha extract versus placebo on sleep in human participants 18 years old and above were considered. Two authors independently read all trials and independently extracted all relevant data. The primary outcomes were sleep quantity and sleep quality. The secondary outcomes were mental alertness on rising, anxiety level, and quality of life.
Results
A total of five randomized controlled trials containing 400 participants were analyzed. Ashwagandha extract exhibited a small but significant effect on overall sleep (Standardized Mean Difference -0.59; 95% Confidence Interval -0.75 to -0.42; I² = 62%). The effects on sleep were more prominent in the subgroup of adults diagnosed with insomnia, treatment dosage ≥600 mg/day, and treatment duration ≥8 weeks. Ashwagandha extract was also found to improve mental alertness on rising and anxiety level, but no significant effect on quality of life. No serious side effects were reported.
Conclusion
Ashwagandha extract appears to has a beneficial effect in improving sleep in adults. However, data on the serious adverse effects of Ashwagandha extract are limited, and more safety data would be needed to assess whether it would be safe for long-term use.
... The anti-anxiety effect of WS was assessed in ten human trials of adults aged 18-75 years ( Table 1). Study populations included participants described as healthy [61], stressed [57,60], diagnosed with general anxiety disorder or a related condition [62,[68][69][70], with insomnia [63,65], or with schizophrenia or schizoaffective disorder [66]. Sample sizes ranged from 39 participants [68] to 130 participants [62], with the majority of studies including between 60 and 80 participants [57,60,61,63,65,66]. ...
... Study populations included participants described as healthy [61], stressed [57,60], diagnosed with general anxiety disorder or a related condition [62,[68][69][70], with insomnia [63,65], or with schizophrenia or schizoaffective disorder [66]. Sample sizes ranged from 39 participants [68] to 130 participants [62], with the majority of studies including between 60 and 80 participants [57,60,61,63,65,66]. ...
... Five human studies have investigated WS for its effects on insomnia in adults aged 18-85 years ( Table 1). Study populations included participants who were healthy [63,64], stressed [60], diagnosed with insomnia [65], or had been experiencing non-restorative sleep [67]. Four of those studies included between 50 [60]. ...
Background
Withania somnifera (WS), also known as Ashwagandha, is commonly used in Ayurveda and other traditional medicine systems. WS has seen an increase in public use worldwide due to its reputation as an adaptogen. This popularity has elicited increased scientific study of its biological effects, including a potential application for neuropsychiatric and neurodegenerative disorders.
Objective
This review aims to provide a comprehensive summary of preclinical and clinical studies examining the neuropsychiatric effects of WS, specifically its application in stress, anxiety, depression, and insomnia.
Methods
Reports of human trials and animal studies of WS were collected primarily from the PubMed, Scopus, and Google Scholar databases.
Results
WS root and leaf extracts exhibited noteworthy anti-stress and anti-anxiety activity in animal and human studies. WS also improved symptoms of depression and insomnia, though fewer studies investigated these applications. WS may alleviate these conditions predominantly through modulation of the hypothalamic-pituitary-adrenal and sympathetic-adrenal medullary axes, as well as through GABAergic and serotonergic pathways. While some studies link specific withanolide components to its neuropsychiatric benefits, there is evidence for the presence of additional yet unidentified active compounds in WS.
Conclusion
While benefits were seen in the reviewed studies, significant variability in the WS extracts examined prevents a consensus on the optimum WS preparation or dosage from treating neuropsychiatric conditions. WS generally appears safe for human use; however, it will be important to investigate potential herb-drug interactions involving WS if used alongside pharmaceutical interventions. Further elucidation of active compounds of WS is also needed.
... Żaden z pacjentów nie zgłosił żadnych działań niepożądanych w okresie objętym badaniem[2]. Podobne wyniki uzyskano również w badaniu przeprowadzonym przez Deshpande A et al. (2020)[3].Pozytywny wpływ na wykładniki jakości snu (SOL, WASO, TST, SE) nie tylko wśród pacjentów z bezsennością, ale również wśród osób zdrowych wykazało badanieLangade D et al. (2021) [1]. ...
... Żaden z pacjentów nie zgłosił żadnych działań niepożądanych w okresie objętym badaniem[2]. Podobne wyniki uzyskano również w badaniu przeprowadzonym przez Deshpande A et al. (2020)[3].Pozytywny wpływ na wykładniki jakości snu (SOL, WASO, TST, SE) nie tylko wśród pacjentów z bezsennością, ale również wśród osób zdrowych wykazało badanieLangade D et al. (2021) [1]. ...
Introduction: Ashwagandha (Withania somnifera) is a plant found on the Indian subcontinent. The health-promoting properties attributed to it have been largely verified in numerous studies over the past 20 years. This article reviews studies on the effects of ashwagandha supplementation on sleep, its deprivation, and studies analyzing the mechanisms determining such effects.
Materials and methods: A review of the literature available in the PubMed database was carried out, using the key words: "ashwagandha" ; "sleep" ; "insomnia", "withania", "somnifera", "withanolide", "withaferin".
Results: Ashwagandha has a positive effect on the quality and length of sleep. It is indicated that it improves sleep parameters among both insomniacs and healthy people. In addition, it has been proven to reduce oxidative stress under conditions of sleep deprivation. Ashwagandha's positive effects on sleep have been shown to be related to its effects on GABA-nergic transmission, and the chemical responsible for the plant's sleep induction is triethylene glycol. Its regular use increases dopamine levels in the brain and could potentially be useful in treating the sleep-related disorder restless legs syndrome.
Conclusions: The use of ashwagandha is a potential direction for treating sleep disorders and improving sleep quality in healthy individuals. There is a need for further development and studies on larger groups of patients to exploit its potential.
... The 28-item General Health Questionnaire (GHQ-28) was used to assess the quality of life [14]. The GHQ-28 has four sub-scales which include: i) physical symptoms (1-7), ii) anxiety symptoms (8)(9)(10)(11)(12)(13)(14), iii) social function (15)(16)(17)(18)(19)(20)(21), and iv) depression symptoms (22)(23)(24)(25)(26)(27)(28). Each sub-scale had seven items with each question scored on a Likert scale (0-3). ...
... Thus, these findings suggest a potentially useful role of Ashwagandha in improving sexual health in otherwise healthy women. Ashwagandha roots extract is reported to be safe for human use with a daily dosage of up to 1,000 mg [26,27]. ...
Background
Poor sexual function is a widespread problem affecting about 40% of women and this may worsen their quality of life. Ashwagandha (Withania somnifera) an adaptogenic herb has been reported to improve sexual satisfaction, sleep, and quality of life in women.
Objective
The purpose of the study was to evaluate the efficacy and safety of standardized Ashwagandha root extract in improving sexual function in healthy females.
Methods
In this prospective, randomized, placebo-controlled study, 80 women between 18 and 50 years of age without any hormonal disturbances and having hypoactive sexual desire disorder (HSDD) with a Female Sexual Function Index (FSFI) score <26, or Female Sexual Distress Scale (FSDS) score >11 were randomized to receive either capsule containing standardized Ashwagandha root extract 300mg twice daily (n=40), or identical placebo (n=40) for eight weeks. Sexual function was assessed using FSFI, FSDS, and Satisfying Sexual Encounters (SSEs). Assessments were done at baseline, four weeks, and eight weeks. Quality of life (QoL) was assessed using the general health questionnaire (GHQ-28) scale, and safety was assessed using clinical signs and symptoms. Repeat measures analysis of variance (ANOVA) was used for the assessment of treatment effect at different time periods. Nominal data were analyzed for differences using Fischer’s Chi-square test.
Results
There was statistically significant improvement (p<0.0001) in FSFI scores with Ashwagandha [14.20 (0.98) at baseline to 22.62 (2.06) at week 8] as compared to placebo [14.17 (0.71) at baseline to 19.25 (2.23) at eight weeks], and this improvement was observed in all sub-scales (desire, arousal, lubrication, orgasm, sexual satisfaction, and pain) of the FSFI scale. There was a greater improvement (p<0.0001) in FSDS scores with AG as compared to placebo. Although not statistically significant (p, 0.078), there was a greater reduction (improvement) in GHQ-28 scores at eight weeks with Ashwagandha as compared to placebo, and this trend was observed for all domains of GHQ-28 (global, physical, psychological, and social function). More women with Ashwagandha had improvement in SSEs at week 4 (p, 0.017) and week 8 (p, 0.002) as compared to placebo. Adverse events were comparable in the two groups. Two women reported nausea and one reported drowsiness with AG, whereas two reported nausea, one reported drowsiness and one reported nausea with drowsiness in the placebo group.
Conclusions
Oral administration of Ashwagandha 300mg twice daily administered for eight weeks improves the female sexual health in otherwise healthy women who do not have any hormonal disturbances. Ashwagandha is a known adaptogen, maintains general well-being and improves vitality.
... studies conducted on: healthy adults (n = 3)(Lopresti et al., 2019;Salve et al., 2019;Tiwari et al., 2021), adults with insomnia (n = 2)Langade et al., 2021), adults with history of chronic stress (n = 3)(Abedon et al., 2008;Chandrasekhar et al., 2012;Choudhary et al., 2017), people with general anxiety disorders (n = 2)(Andrade et al., 2000;Khyati & Anup, 2013), subjects with schizophrenia or schizoaffective disorder (n = 1)(Chengappa et al., 2018), and bipolar adults (n = 1)(Chengappa et al., 2013). Type of questionnaires that were used to assess anxiety includes Hamilton Anxiety Rating Scale (HAM-A) and Depression Anxiety Stress Scale (DASS). ...
... Perceived Stress Scale (PSS), Recovery-Stress Questionnaire for Athletes (RESTQ), Depression, Anxiety, and Stress Scale À21 (DASS-21), modified Hamilton anxiety (mHAM-A) scale for stress were used to evaluate stress. Moreover, based on Cochrane Collaboration Risk of Bias guideline: six trials were good(Chengappa et al., 2018;Choudhary et al., 2017;Langade et al., 2019;Langade et al., 2021;Lopresti et al., 2019;Tiwari et al., 2021), five trials had a fair quality(Abedon et al., 2008;Chandrasekhar et al., 2012;Chengappa et al., 2013;Khyati & Anup, 2013;Salve et al., 2019), and one trial was poor(Andrade et al., 2000) ...
Clinical trial studies revealed conflicting results on the effect of Ashwagandha extract on anxiety and stress. Therefore, we aimed to evaluate the effect of Ashwagandha supplementation on anxiety as well as stress. A systematic search was performed in PubMed/Medline, Scopus, and Google Scholar from inception until December 2021. We included randomized clinical trials (RCTs) that investigate the effect of Ashwagandha extract on anxiety and stress. The overall effect size was pooled by random‐effects model and the standardized mean difference (SMD) and 95% confidence interval (CIs) for outcomes were applied. Overall, 12 eligible papers with a total sample size of 1,002 participants and age range between 25 and 48 years were included in the current systematic review and meta‐analysis. We found that Ashwagandha supplementation significantly reduced anxiety (SMD: −1.55, 95% CI: −2.37, −0.74; p = .005; I2 = 93.8%) and stress level (SMD: −1.75; 95% CI: −2.29, −1.22; p = .005; I2 = 83.1%) compared to the placebo. Additionally, the non‐linear dose–response analysis indicated a favorable effect of Ashwagandha supplementation on anxiety until 12,000 mg/d and stress at dose of 300–600 mg/d. Finally, we identified that the certainty of the evidence was low for both outcomes. The current systematic review and dose–response meta‐analysis of RCTs revealed a beneficial effect in both stress and anxiety following Ashwagandha supplementation. However, further high‐quality studies are needed to firmly establish the clinical efficacy of the plant.
... 45 Similarly, many other studies have shown significant results for Ashwagandha in improving sleep efficiency, overall sleep time, and sleep latency through mechanisms involving increased expressions of gamma-aminobutyric acid A (GABAA), gamma-aminobutyric acid B1 (GABAB1), and serotonin receptors in the brain. 46, 47 Ashwagandha has also been reported to demonstrate beneficial effects on the cardiovascular system by enhancing overall cardio-respiratory endurance (CRE). For instance, a trial by Tiwari et al. ...
Sleep is a complex physiological phenomenon crucial for health. Despite this, millions suffer from sleep disorders, contributing to a range of health issues, particularly cardiovascular diseases (CVD). The pathophysiological mechanisms linking sleep disorders, such as insomnia and obstructive sleep apnea (OSA), to cardiovascular risk factors include disruptions in inflammatory, autonomic, and metabolic pathways. Increased sympathetic nervous system activity, chronic inflammation, and metabolic dysregulation stemming from poor sleep can lead to conditions like hypertension, obesity, and insulin resistance, significantly elevating the risk for CVD. This article reviews the connection between sleep quality and cardiovascular disease risks. Sleep disorders (i.e., insomnia and OSA) have been found to impact cardiovascular risk factors adversely. Studies have found an association between abnormal sleep and increased cardiovascular morbidity and mortality by higher risks of hypertension, diabetes, obesity, and dyslipidemia. The review also discusses non-pharmacological interventions, such as relaxation training, Cognitive behavioral therapy for insomnia (CBT-I), and red-light therapy, which have shown efficacy in improving sleep quality and reducing cardiovascular risks. Dual orexin receptor antagonists and Ashwagandha promise to enhance sleep quality and cardiovascular health, but further research is needed. Addressing sleep disorders and promoting healthy sleep practices are essential for mitigating the global burden of cardiovascular diseases, underscoring the need for continued research and effective public health interventions.
... A prospective, randomized, double-blind, single-center, placebo-controlled study conducted at Sudbhawana Hospital in Varanasi, India, showed that Ashwagandha root extract (600 mg daily) is beneficial in normalizing thyroid function in patients with subclinical hypothyroidism [137]. Other randomized studies, also carried out on small groups, have indicated efficacy in improving the quality of sleep in patients with insomnia [138], reducing stress and anxiety [139], sexual well-being, increasing serum testosterone levels in adult men [140], and improving female sexual health [141]. It probably relieves these conditions mainly through hypothalamic-pituitary-adrenal modulation as well as through GABAergic and serotonergic pathways [142]. ...
Hypothyroidism is one of the most common endocrinopathies worldwide, the treatment of which is based on replacement therapy with levothyroxine. However, this seemingly simple treatment method is fraught with many difficulties and frequent dissatisfaction among patients. In fact, differences in response to levothyroxine probably depend on a complex interaction between individual, environmental, genetic, and epigenetic factors that are still not sufficiently understood. Immunological disturbances, underlying Hashimoto's disease, the most common cause of hypothyroidism, probably play a significant role in these relationships. Indeed, a growing number of studies indicate that autoimmunity through activation of low-grade inflammation can lead to impaired absorption, transport, metabolism, and action of thyroid hormones. This review provides an up-to-date overview of the causes responsible for both the difficulty in achieving target thyrotropin levels and persistence of nonspecific symptoms despite adequate hormone replacement from an immunoendocrine perspective. Understanding these mechanisms points to a new direction in the approach to hypothyroidism, indicating the need for new personalized treatment strategies.
... Other findings of the study include the improvement in the severity of insomnia in subjects assigned to milks enriched with ashwagandha 250 mg and 600 mg, particularly at doses of 600 mg, as well as a reduction in daytime sleepiness. These results are consistent with research studies showing that ashwagandha supplements can act as a sleep aid in subjects with insomnia symptoms [20,27,[34][35][36][37]. Studies in animal models have shown that ashwagandha root extracts exert sleep-promoting activity through the GA-BAergic system [38,39]. ...
A randomized, double-blind and controlled study was conducted to assess the effectiveness of the intake of 250 mL of lactose-free skimmed milk enriched with ashwagandha (Withania somnifera) alone or combined with tryptophan vs. non-enriched milk (control) on the subjective quality of sleep in healthy adults with sleep problems. The duration of supplementation was 90 days. Fifty-two eligible subjects were assigned to the study arms of ashwagandha 250 mg, ashwa-gandha 250 mg plus tryptophan 175 mg, ashwagandha 600 mg, and control with 13 subjects in each group. It was hypothesized that ashwagandha plus tryptophan could be superior to ashwagandha alone for improving sleep-related variables. Changes in the visual analogue scale (VAS) for sleep quality were significantly higher in the three experimental groups as compared with controls (p = 0.014). Improvements in the subscales of the Pittsburg Sleep Quality Index (PSQI) were found in all groups, but between-group differences were not significant. In the index of insomnia severity, decreases were higher in the three experimental groups as compared with controls especially in the group of ashwagandha 600 mg. Daytime somnolence was also reduced in the three experimental groups. Changes in anxiety levels and Morningness-Eveningness Questionnaire were not observed. The study products did not elicit changes in body composition and were well tolerated and safe. The data did not support the hypothesis, as the combination of ashwagandha and tryptophan did not show greater benefits in improving sleep quality than ashwagandha alone. However, the results from the three experimental groups containing ashwagandha were more favorable compared to the placebo group.
... Research indicates that Ashwagandha supplementation leads to notable enhancements in various sleep parameters, including mental alertness, sleep quality, reduced sleep onset latency, and improved sleep efficiency. Interestingly, these improvements were found to be more pronounced in individuals with insomnia compared to those without sleep disturbances [18] . Withania somnifera demonstrates effectiveness in alleviating anxiety symptoms and holds promise as a potential anxiolytic, as indicated by Hamilton Anxiety Rating Scale scores. ...
Withania somnifera, also known as Ashwagandha, is a key herb in Ayurvedic medicine, celebrated for its ability to rejuvenate and promote longevity. It is believed to support overall wellness, offering neuroprotective, anti-inflammatory, and adaptogenic benefits. This study aims to evaluate how Ashwagandha (Withania somnifera) supplementation impacts stress levels, psychological well-being, and resilience, assessing its overall effectiveness as an adaptogen. Stress, be it physical or psychological, activates a response involving the nervous, endocrine, and immune systems through various mechanisms, initially aiding in handling challenges but becoming detrimental when perceived as intense, repetitive, or prolonged, contributing to conditions like depression, anxiety and cognitive decline. Ashwagandha reduces morning cortisol and DHEA-S levels and increases heart rate variability. It improves sleep quality, alleviates anxiety symptoms, and may help with depression due to its components, such as alkaloids and withanolides. Additionally, it reduces fatigue and enhances overall well-being and happiness. It is important that Ashwagandha supplementation is safe and does not cause side effects, making it an attractive alternative for supporting health and well-being. Ashwagandha supplementation, due to adaptogenic qualities, appears promising in addressing stress and stress-related disorders, as well as enhancing overall well-being. Further research is warranted to fully explore its potential role in conventional health strategies.
... W. somnifera boosts macrophage nitric oxide synthase activity that assists immune cells in reducing microbial infection (15), stimulates and mobilizes macrophages, and potentiates lysosomal enzymes for anti-inflammatory activity in rodents (16). Furthermore, W. somnifera has been found to improve cognitive function, reduce stress and anxiety (17), improve sleep quality (18), and provide other benefits that include neuroprotection, anti-inflammatory, anti-tumor, and cardioprotection (19). Withanolides, flavonoids, phenolic acids, steroidal alkaloids, saponins, and tannins are the most bioactive phytochemicals that play pivotal roles in various pharmacological activities of W. somnifera extracts (20,21). ...
Background: The use of botanical medicine has been demonstrated as a potential strategy to manage or treat a variety of health issues. Terminalia chebula (Retz) fruit and Withania somnifera (L.) Dunal roots are important medicinal herbs described in Ayurveda and traditional therapy for diverse health benefits. Objective: This pilot study aimed to evaluate the immune function-enhancing potential of a unique blend of T. chebula fruit and W. somnifera root extracts, LN20189, in healthy men and women. Methods: Forty healthy volunteers (age: 35–60 years) were randomized into two groups receiving either LN20189 (500 mg per day) or a matched placebo over 28 consecutive days. The total T-cell population was the primary efficacy measure in this study. The secondary efficacy measures included counts of CD4, CD8, natural killer (NK) cells, serum levels of interleukin-2 (IL-2), interferon-gamma (IFN-γ), total immunoglobulin-G (IgG), and Immune Function Questionnaire (IFQ) scores. Safety parameter assessments were also conducted. Results: Post-trial, in LN20189-supplemented subjects, T cells, CD4, NK cells count, and the CD4:CD8 ratio were increased by 9.32, 10.10, 19.91, and 17.43%, respectively, as compared to baseline. LN20189 supplementation increased serum IFN-γ and IgG levels by 14.57 and 27.09% from baseline and by 13.98 and 21.99%, compared to placebo, respectively. Also, the IFQ scores in the LN20189 group were 84.68% (vs. baseline) and 69.44% (vs. placebo) lower at the end of the trial. LN20189 improved the study volunteers’ cellular and humoral immune functions. Conclusion: In summary, LN20189 supplementation was found tolerable and improved the key cellular and humoral factors of the immune system and helped improve immune function of the trial volunteers.
... Studies reported no significant change in body weight, body temperature, body mass index, respiratory rate, systolic and diastolic blood pressure, hematological and biochemical parameters, and thyroid hormone, suggesting that Withania somnifera root extract is well-tolerated in healthy male and female volunteers for 8 weeks. Langade et al. [163] demonstrated safety of Withania somnifera in healthy volunteers and insomnia patients treated with Withania somnifera root extract capsules 300 mg twice daily for 8 weeks. ...
Inflammaging, a coexistence of inflammation and aging, is a persistent, systemic, low-grade inflammation seen in the geriatric population. Various natural compounds have been greatly explored for their potential role in preventing and treating inflammaging. Withania somnifera has been used for thousands of years in traditional medicine as a nutraceutical for its numerous health benefits including regenerative and adaptogenic effects. Recent preclinical and clinical studies on the role of Withania somnifera and its active compounds in treating aging, inflammation, and oxidative stress have shown promise for its use in healthy aging. We discuss the chemistry of Withania somnifera, the etiology of inflammaging and the protective role(s) of Withania somnifera in inflammaging in key organ systems including brain, lung, kidney, and liver as well as the mechanistic underpinning of these effects. Furthermore, we elucidate the beneficial effects of Withania somnifera in oxidative stress/DNA damage, immunomodulation, COVID-19, and the microbiome. We also delineate a putative protein–protein interaction network of key biomarkers modulated by Withania somnifera in inflammaging. In addition, we review the safety/potential toxicity of Withania somnifera as well as global clinical trials on Withania somnifera. Taken together, this is a synthetic review on the beneficial effects of Withania somnifera in inflammaging and highlights the potential of Withania somnifera in improving the health-related quality of life (HRQoL) in the aging population worldwide.
... • The Statin groups medicines are used for hyperlipidemia, these are having headache, sleep problem, feeling sick, and dizziness etc [16]. To counter these side effects a classical Ayurved drug like Manasmitra vatakam [17] or Ashwagandha [18,19] may combine in suitable proportions to pacify side effects of Statin drug. • Acidity is a widespread problem among workers working in shifts, in India most common allopathic antacid drug consumed is Gelusil [20] having side effects like constipation, diarrhoea etc. ...
Drugs are an integral part of treatment in health care, it is a belief that the drugs should be free from side effects should be safe and not to create any disease. The chemical or allopathic drugs which are having some side effects may be combined with Ayurveda herbal drugs to pacify their side effects or bring to minimal level. Another aspect is that the Ayurved herbal drugs are slow and weak in action, but quite safe, on other side the allopathic drugs are comparatively fast, bit strong but with some side effects. If these two are combined like an example of anti-diabetic allopathic drug metformin which is most prescribed. The Metformin is having some side effects like diarrhoea, metallic test, loss of appetite etc., on other side ayurvedic anti-diabetic drug Andrographis paniculate may be a safe combination as Andrographis has protective effects on gastrointestinal tract also. Such integrative approaches will be an ideal in developing integrative potential and safe drugs. This strategy will work effectively and may find an innovative solution for lifestyle related diseases.
... At the conclusion of the study, there was no discernible change in the values of the aforementioned indicators between the 40 participants in the extract-using group and the 40 participants in the placebo-taking group. Triiodothyronine, thyroxine, and TSH levels were measured in the blood to assess thyroid function; however, no appreciable changes in these hormone levels were observed (Langade et al., 2021;Verma et al., 2021). ...
Ashwagandha ( Withania somnifera ), which is widely used in Ayurveda and other system of medicine, is best known for its ability to reduce depression and associated problems. Notably, important constituents of the body such as enzymes are intimately associated with the chemicals present in plants; hence supplementation is necessary to maintain overall health. In this study, reports of experimental studies were collected primarily from various scientific sources like Scopus, Springer, PubMed, Google Scholar etc. The findings of the review suggested that AS extract and its phytoconstituents significantly reduced depression and also modulated oxidative stress and inflammation which play a major role in neurological disorders including depression. The growing amount of research on ashwagandha emphasizes its potential as a useful natural depression remedy. However, further preclinical and clinical research is necessary to substantiate present observations to establish better methods for assessing the ashwagandha safety, effectiveness, bioavailability, purity, and precise mechanisms of action.
... Previous studies investigating ashwagandha's effects on stress and anxiety, with both men and women, and using a similar dosage to the current study, had sample sizes ranging from 60 to 80 participants, with effect sizes ranging from 0.63 to 0.74 (Abedon et al., 2008;Chandrasekhar et al., 2012;Langade et al., 2019;Langade et al., 2021;Lopresti et al., 2019a;Salve et al., 2019). We predicted a more conservative effect size of 0.5, thereby requiring a sample size of 51 per group. ...
Background
Stress is a state of homeostasis in the body being challenged, resulting in a systemic response. It has become more prevalent in recent years and affects mental and physical health.
Aims
Evaluate the effects of ashwagandha on stress, fatigue, and sex hormones in overweight or mildly obese men and women with self-reported stress and fatigue.
Methods
Two-arm, parallel-group, 12-week, randomized, double-blind, placebo-controlled trial on overweight or mildly obese men and women aged 40–75 years, supplementing with 200 mg of an ashwagandha root extract (Witholytin®) twice daily.
Results/Outcomes
Supplementation with ashwagandha was associated with a significant reduction in stress levels based on the Perceived Stress Scale (primary outcome); however, the improvements were not significantly different to the placebo group ( p = 0.867). Based on the Chalder Fatigue Scale, there was a statistically significant reduction in fatigue symptoms in the ashwagandha group compared to the placebo group ( p = 0.016), and participants taking ashwagandha also experienced a significant increase in heart rate variability ( p = 0.003). However, there were no significant between-group differences in other self-report outcome measures. In the men taking ashwagandha, there was a significant increase in the blood concentrations of free testosterone ( p = 0.048) and luteinizing hormone ( p = 0.002) compared to the placebo group.
Conclusions/Interpretation
The results of this study suggest that in overweight middle-to-older age adults experiencing high stress and fatigue, compared to the placebo, ashwagandha did not have a significantly greater impact on perceived stress levels. However, based on secondary outcome measures, it may have anti-fatigue effects. This may be via its impact on the autonomic nervous system. However, further research is required to expand on these current findings.
... It is statistically proven that inhaling lemongrass essential oil may improve cognitive function and mood in healthy women while not affecting physiological status (Sriraksa et al., 2018). Likewise, Ashwagandha's root extract is proven to improve sleep quality and help with insomnia management (Langade et al., 2021). ...
Herbal tea, also known as tisane, is a beverage made from the infusion or decoction of plant material in hot water. True tea comes from the Camellia sinensis plant, while tisane (herbal tea) comes from a water-based infusion of herbs, spices, flowers, leaves etc. This study aimed to formulate and determine the nutraceutical value (proximate analysis), phytochemical value (total phenolic content) and in-vivo toxicity of the different medicinal plants used to prepare three different types of herbal tea formulations. Natural Product Research Laboratory (NPRL)-1 [Asparagus officinalis L., Phyllanthus emblica L., Mentha piperita L., Elettaria cardamomum (L.) Maton and Camellia sinensis (L.) Kuntze], NPRL-2 [Ocimum tenuiflorum L., Bergenia ciliate (Haw.) Sternb., Elettaria cardamom (L.) maton and Camellia sinensis (L.) Kuntze] and NPRL-3 [Salvia rosmarinus Spenn., Cymbopogon citratus (DC.) Stapf, Senegalia catechu (L.f.) P.J.H.Hurter & Mabb. Elettaria cardamomum (L.) Maton and Withania somnifera (L.) Dunal] herbal tea formulations were prepared from these selected medicinal plants. They were respectively tested for their properties. All the plants included were highly nutritional and none were found toxic. The results suggested that herbal tea made up of these potent plants’ parts can be a good choice for health-promoting benefits. These formulations could further be studied for their other beneficial activities.
... In 2020, Ashwagandha experienced the greatest sales increase in the US mainstream multi-outlet channel (grocery outlets, drug outlets, and selected retailers across mass merchandisers) by 185.2% respect to 2019, reaching over $31 million sales and ranking 12 th in the US herbal supplements retail channel [10]. Numerous studies have demonstrated the benefits of Ashwagandha on physical performance [11][12][13][14][15][16] as well as for individuals with medical conditions such as diabetes [17][18][19], cognitive dysfunction [20][21][22], infertility [23][24][25], and anxiety and stress [26,27]. Recent systematic reviews have supported such findings [28, 29 •, 30, 31, 32•] corroborated the effects of Ws on strength and power, cardiorespiratory fitness, and fatigue and recovery, while the systematic review conducted by Durg et al. [29•] demonstrated improvements in blood glucose (postprandial blood glucose and HbAlc) levels and lipid profile (total cholesterol, triglycerides, low-density lipoprotein [LDL], very low-density lipoprotein [VLD], and highdensity lipoprotein [HDL] levels) in diabetic patients. ...
Purpose of Review
Withania somnifera (L.) Dunal (Ws) is a common herb plant that has been used for centuries to treat a wide range of conditions, particularly certain chronic diseases due to its antidiabetic, cardioprotective, antistress, and chondroprotective effects, among many others. No conclusive evidence, however, exists about the potential health effects of Ws in adults without chronic conditions. We aimed to evaluate the current evidence on the health benefits of Ws supplementation in healthy adults.
Recent Findings
Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed studies indexed in Web of Science, Scopus, and PubMed to assess the effects of Ws on hematological and biochemical markers, hormonal behavior, and oxidant response in healthy adults. Original articles published up to March 5, 2022, with a controlled trial design or pre-post intervention design, in which supplementation of Ws was compared to a control group or data prior to intervention were included. Among 2,421 records identified in the search, 10 studies met the inclusion criteria. Overall, most of the studies reported beneficial effects of the Ws supplementation, and no serious adverse events were reported. Participants supplemented with Ws displayed reduced levels of oxidative stress and inflammation, and counterbalanced hormone levels. No evidence of the beneficial effects of Ws supplementation on hematological markers was reported.
Summary
Ws supplementation appears to be safe, may regulate hormone levels, and has potent anti-inflammatory and antioxidant effects. However, further studies are needed to elucidate the relevance of its application.
... As substitutes and supplements for sleep medicines, natural plant extracts, such as Valeriana officinalis L. (valerian) [6], Humulus lupulus L. (hop) [7], Ziziphus jujuba Mill. (jujube) [8], Withania somnifera L. Dunal (Ashwagandha) [9], and Matricaria chamomilla L. (chamomile) [10], have been actively examined for their sleep enhancing function. ...
Ashwagandha (Withania somnifera L. Dunal), an Indian medicinal plant that has been used for centuries to treat insomnia, exhibits a variety of biological activities, such as improving cognitive function, immunity and anxiety. In this study, the effect of enzyme-treated Ashwagandha root extract (EA) and on sleep was evaluated using rodent models. Starch contained in the Ashwagandha root extract was removed by amylase treatment to prepare EA. To evaluate the sleep-promoting activity of EA, a pentobarbital-induced sleep test and electroencephalogram analysis were performed. In addition, the sleep-promoting mechanism of EA was elucidated by analyzing the expression of sleep-related receptors. In the pentobarbital-induced sleep test, EA dose-dependently increased sleep duration. Additionally, electroencephalogram analysis revealed that EA significantly increased δ-wave and non-rapid eye movement sleep times, which are involved in deep sleep, thereby improving sleep quality and quantity. EA also effectively relieved caffeine-induced insomnia symptoms. Furthermore, the γ-aminobutyric acid (GABA) content in the brain and mRNA and protein expression of GABAA, GABAB1, and serotonin receptors were significantly increased by EA compared to the normal group. In particular, EA showed sleep-promoting activity by binding to various GABAA receptor sites. Collectively, EA exhibited sleep-promoting activity through the GABAergic system and may be used as a functional material to improve sleep deprivation.
... 68,70] and SOL(18/32) [43,45,47,49e54,56e58,61,63,64, 67,68,70,71]. In contrast, only five studies focused on actigraphy measures on NAWK[48,53,62,64], while total wake time (TWT) (consisting of SOL þ WASO) was reported in three studies ...
Actigraphy has a consolidated role in Insomnia and Circadian Rhythm Sleep-Wake Disorders (CRSWD) and recent studies have highlighted the use of actigraphy for narcolepsy and REM sleep behaviour disorder (RBD). This review aims at summarising the results of studies published over the last decade regarding the use of actigraphy. Thirty-five studies proved eligible, and results were analysed separately for insomnia, narcolepsy and RBD. Actigraphy showed to consistently differentiate insomnia patients from healthy controls. Furthermore, the application of advanced analytical techniques has been shown to provide both unique insights into the physiology of insomnia and sleep misperception and to improve the specificity of actigraphy in detecting wakefulness within sleep periods. Regarding narcolepsy, several studies showed that actigraphy can detect peculiar sleep/wake disruption and the effects of pharmacological treatments. Finally, although the number of studies in RBD patients is still limited, the available evidence indicates a reduced amplitude of the activity pattern, sleep-wake rhythm dysregulation and daytime sleepiness. Therefore, the potential use of these markers as predictors of phenoconversion should be further explored. In conclusion, quantitative actigraphy presents a renewed interest when considering the possibility of using actigraphy in clinical sleep medicine to diagnose, monitor, and follow sleep disorders other than CRSWD.
... improvement in sleep quality with ASW [90]. In this study, 40 subjects with insomnia and 40 healthy subjects were randomized to receive either 600 mg of ASW or placebo in equal numbers (20 in each arm) for 8 weeks. ...
Introduction
Ashwagandha (ASW) is the extract of the plant Withania somnifera. It is widely used in complementary, alternative and integrative medicine (CAIM) but is little discussed in mainstream modern medical literature.
Areas covered
We performed a review of potential pharmacotherapeutic properties of ASW. Studies were sourced from relevant online and offline databases. In animal models, ASW displays antioxidant activity. It has GABAergic and other neurotransmitter modulatory effects. It reduces apoptosis and promotes synaptic plasticity. It improves cognition and reverses induced cognitive deficits. It attenuates indices of stress. In human subjects, ASW enhances adaptogenesis in healthy adults. It modestly benefits generalized anxiety disorder and obsessive-compulsive disorder, and symptom severity in schizophrenia, substance use disorders, and attention deficit hyperactivity disorder. It improves sleep quality.
Expert opinion
ASW may confer modest benefit in certain neuropsychiatric conditions. Its benefits may arise from induction of neuroplasticity, antioxidant and anti-inflammatory effects, and modulation of GABA and glutamate as well as other neurotransmitters. The antioxidant and anti-inflammatory actions may also benefit neurodegenerative states. Reports of clinical benefit with ASW must be interpreted with caution, given the paucity of randomized clinical trials (RCTs). Greater methodological rigor is necessary before clinical recommendations on ASW can be confidently made.
... Ashwagandha (ASH) (Withania somnifera), an Ayurvedic adaptogenic herb, has been used historically as a rejuvenator, aphrodisiac, tonic, hypnotic, diuretic, astringent, antibiotic, and stimulant. 12 Early clinical evidence supports its use to treat anxiety and depression, 13 compromised immunity, 14 infertility, 15 insomnia, 16 neurodegenerative diseases, 17 and cancer. 18 A recent meta-analysis provided a summary of human trials citing ASH as a stand-alone treatment of mental and physical conditions. ...
The purpose of this study was to examine the impact of ashwagandha (ASH) (Withania somnifera) on sleep, perceived stress, and cravings in a college student population. Sixty healthy students were screened/enrolled into a 30-day double-blinded placebo (PLA)-controlled intervention (700 mg daily, full spectrum extract of ASH root). Anthropometrics, demographics, and validated questionnaires assessing physical activity, restorative sleep, perceived stress, and food cravings were assessed before and after the study. Descriptive statistics, Pearson's correlations, and point biserial correlations were used to screen the data. For sleep and stress, a nonsignificant mixed (group × time) multivariate analysis of variance (MANOVA) was followed by one-way MANOVA (time on sleep/stress) and one-way multivariate analysis of covariance (MANCOVA) (group on sleep/stress, using initial sleep as a covariate) as follow-up tests. Further follow-up tests for this MANCOVA showed group membership affected final sleep (58.4 ± 12.4 vs. 48.2 ± 15.0 ASH vs. PLA respectively, P < .05) using initial sleep as a covariate. Initial sleep (confounder) affected final stress, but not final sleep. Mixed analysis of variance (group × time) showed an interaction effect on food cravings, where the ASH group experienced lower cravings than the PLA group over time at end of study. The 30-day intervention was shorter than most other studies where more pronounced stress differences were seen at six weeks, indicating ASH may need the longer time period to show more pronounced stress relieving differences. ASH can be an effective safe intervention in young adult populations to help manage stress and its detrimental impacts on sleep and satiety in as little as 30 days. Clinical Trial Registration number-NCT05430685.
... It was also shown to improve memory, cognition, and body weight management by optimizing metabolism, sleep, and other factors. [34][35][36] The increase in serum testosterone using ashwagandha has been reported earlier. 22 The present study has demonstrated that the ashwagandha root extract powder effectively enhances male libido in adult men with normal testosterone and prolactin levels. ...
Background and Aim
In Ayurveda, ashwagandha is a popular plant for promoting youthful energy, longevity, and overall well‐being. It is also an excellent aphrodisiac herb that aids in the improvement and maintenance of normal sexual health. The present study aims to evaluate the effect of ashwagandha root extract on improving sexual health in adult males.
Methods
In this 8‐week randomized, double‐blind, placebo‐controlled study, we investigated the aphrodisiac property of an ashwagandha root extract in adult males. Fifty participants with lower sexual desire were randomly allocated to take 300 mg of ashwagandha root extract or placebo capsules twice daily. Outcomes were measured using the derogatis interview for sexual functioning‐male (DISF‐M) questionnaire, serum testosterone, serum prolactin, and short‐form survey—36 quality of life questionnaire before and after the intervention.
Results
Compared to placebo, ashwagandha root extract supplementation was associated with a statistically significant increase in the total DISF‐M scores (mean difference −9.8; 95% confidence interval, −10.73 to −8.87; p < 0.0001; t‐test). It was also associated with a statistically significant increase in serum testosterone levels (−66.52; −80.70 to −52.34; p < 0.0001; t‐test). However, the prolactin level did not change after intervention in both the ashwagandha and placebo groups (−1.06; −2.78 to 0.66; p > 0.05).
Conclusion
These findings suggest that ashwagandha demonstrated a significant subjective perception of sexual well‐being and assisted in increasing serum testosterone levels in the participants.
... 166 Ashwagandha extract has been shown to result in significant improvement in overall sleep compared to placebo in the dosage of ≥600 mg/day. 167 Regarding its potential putative effects in neurological and inflammatory disorders, withaferin A -bioactive constituent from Withania somnifera -has been shown to mitigate inflammatory cytokines, including nuclear factor kappa-B (NF-κB) and tumor necrosis factor-alpha (TNF-α), as well as diminish the expression of pro-fibrotic proteins. 168 Withaferin A also induces heat shock proteins that are instrumental in promoting protein folding. ...
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the loss of upper and lower motor neurons in the motor cortex, brain stem, and the anterior horn of the spinal cord. The majority of ALS cases are classified as sporadic (sALS). There is a growing concern regarding the increased incidence in the number of sporadic ALS cases across the world, projected to increase by almost 70% in the next two decades. The etiology of sporadic ALS is currently unknown; however, epidemiological studies point to possible exposure of environmental triggers, including trauma and infections as risk factors for the development of motor neuron pathology. On a pathological basis, protein misfolding with the accumulation of cytoplasmic inclusions of TDP-43 are regarded as the hallmark feature of ALS pathogenesis. The cellular mechanisms that lead to protein aggregation are not completely understood, but appear to involve defects in autophagy, an intracellular autodigestive process that degrades misfolded proteins like TDP-43. This review will be split into two portions: (1) discuss the evidence regarding how various environmental risk factors, such as infections agents and physical trauma, can lead to neuropathological changes by disrupting autophagy in ALS; (2) discuss potential treatment options in the management of each environmental factor previously discussed.
... According to the 5 th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and the 3 rd edition of the International Classification of Sleep Disorders (ICSD-3) [13,14] , dissatisfaction with sleep time or quality must occur at least three nights a week within 3 mo to be diagnosed as chronic insomnia [15] . In addition, patients diagnosed with insomnia symptoms have enough sleep time in time, but they still have sleep problems and cause at least one related daytime effect [16] . The various causes of insomnia can be divided into susceptible factors, predisposing factors and persistent factors. ...
... Deshpande et al. showed improved sleep quality in healthy patients suffering from nonrestorative sleep after treatment with a standardized extract of ashwagandha [75]. In a recent clinical study, Langade et al. verified the use of an extract of ashwagandha both as an anxiolytic and to improve symptoms of insomnia as compared to a placebo [76]. Taken together, these studies show that ashwagandha can be used as an anxiolytic, as well as for treating insomnia and enhancing sleep quality. ...
Sleep disorders are common among the general population and can generate health problems such as insomnia and anxiety. In addition to standard drugs and psychological interventions, there are different complementary plant-based therapies used to treat insomnia and anxiety. This review aimed to find and examine the most recent research on the use of herbal medicines for treating anxiety and insomnia as compiled from clinical trials, as well as to assess the safety and efficacy of these medicines and to elucidate their possible mechanisms of action. The process entailed a search of PubMed, Scopus, and the Cochrane Library databases from 2010 to 2020. The search terms included “sleep disorder”, “insomnia”, “sedative”, “hypnotic”, “anxiety”, “anxiolytic”, and “clinical trial”, combined with the search terms “herbs” and “medicinal plants”, in addition to individual herbal medicines by both their common and scientific names. This updated review, which focuses mainly on clinical trials, includes research on 23 medicinal plants and their combinations. Essential oils and their associations have also been reviewed. The efficacy of medicinal plants depends on treatment duration, types of study subjects, administration route, and treatment method. More clinical trials with an adequate, standardized design are necessary, as are more preclinical studies to continue studying the mechanisms of action. As a result of our work, we can conclude that the 3 plants with the most potential are valerian, passionflower, and ashwagandha, with the combination of valerian with hops and passionflower giving the best results in the clinical tests.
... Both groups showed significant improvements in sleep onset latency (p <0.0001), sleep efficiency (p < 0.0001), wake after sleep onset (p < 0.040) and total sleep time (p < 0.002). Improvements were also seen in anxiety score (p < 0.05), mental alertness on rising (p = 0.01) and sleep quality (p < 0.05) [163]. ...
Functional beverages can be a valuable component of the human diet with the ability to not only provide essential hydration but to deliver important bioactive compounds that can contribute to chronic disease treatment and prevention. One area of the functional beverage market that has seen an increase in demand in recent years are beverages that promote relaxation and sleep. Sleep is an essential biological process, with optimal sleep being defined as one of adequate duration, quality and timing. It is regulated by a number of neurotransmitters which are, in turn, regulated by dietary intake of essential bioactive compounds. This narrative review aimed to evaluate the latest evidence of the sleep promoting properties of a selection of bioactive compounds (such as L-theanine and L-tryptophan) for the development of a functional beverage to improve sleep quality; and the effectiveness of traditional sleep promoting beverages (such as milk and chamomile). Overall, the bioactive compounds identified in this review, play essential roles in the synthesis and regulation of important neurotransmitters involved in the sleep-wake cycle. There is also significant potential for their inclusion in a number of functional beverages as the main ingredient on their own or in combination. Future studies should consider dosage; interactions with the beverage matrix, medications and other nutraceuticals; bioavailability during storage and following ingestion; as well as the sensory profile of the developed beverages, among others, when determining their effectiveness in a functional beverage to improve sleep quality.
This work presents the results of field research conducted in 2023-2024 in the Czudec commune (Podkarpackie voivodeship). The aim of the study was to analyze the species composition of herbaceous plant flora at selected sites, with particular emphasis on medicinal species, and to indicate the places of their greatest concentration for the purpose of obtaining them from the natural state.
During the research, a herbarium and a systematic floristic list were prepared, which included 286 species of herbaceous plants belonging to 45 plant families. The analysis of available literature and internet data allowed to determine that 158 recorded species have medicinal properties and are used in conventional and/or unconventional or folk medicine.
Background
Sleep disorders, specifically insomnia, are recognized as global public health concerns. The present study is to evaluate the potential effects of a multi-ingredient formula through a multimodal approach on sleep quality in people with insomnia. The study supplement contained bovine colostrum and egg yolk extracts, ashwagandha root extract, lavender oil, pyridoxal-5-phosphate, melatonin, GABA, and magnesium. Colostrum and egg yolk extracts have been shown to support immune system function and thus likely support sleep health. Ashwagandha root extract, lavender oil, pyridoxal-5-phosphate, melatonin, GABA, and magnesium have been shown to help sleep health and quality via different mechanisms of action.
Methods
A total of 30 healthy adults with self-reported symptoms of insomnia, divided into placebo and treatment groups, completed a 6-week randomized, double-blinded, placebo-controlled crossover study (1-week washout, 2-week intervention, 1-week washout, and 2-week intervention, sequentially). Participants were instructed to fill out Insomnia Severity Index (ISI) and the Leeds Sleep Evaluation Questionnaire (LSEQ) survey weekly, and keep a sleep diary daily, which were used to assess their sleep quality. Saliva samples were taken from participants before and after each 2-week treatment period to measure salivary melatonin level. Participants were instructed to wear a Fitbit Inspire 2 device to track their sleep and wake data. Linear mixed model ANOVA was used to evaluate statistics for the study.
Results
Study supplement significantly improved sleep quality of participants compared to placebo group, specifically difficulty falling asleep (p < 0.01). The study supplement also significantly improved the number of awakenings during the night compared to baseline (p < 0.01). Overall sleep health was improved, specifically sleep quality (wakefulness) (p < 0.01). Study supplement also significantly improved salivary melatonin levels compared to placebo group (p < 0.01). Some limitations of the study include a lack of controlled environment and a heterogeneous population, among others.
Conclusions
The preliminary findings observed in the present study showed that the study supplement improved sleep health and quality for people with insomnia. The importance of finding effective and safe solutions for poor sleep and insomnia cannot be overstated.
Study registration
ClinicalTrials.gov NCT05368909 “Clinical Study to Assess a Dietary Supplement on Sleep Health and Quality “, registered May 10, 2022. https://clinicaltrials.gov/study/NCT05368909.
Background: Ashwagandha root extract offers broad therapeutic benefits, enhancing physical performance, mental health, and cognitive function, making it a valuable adaptogenic and nootropic solution. Methods: This study reviews clinical trials on Ashwagandha's effects in adults, analyzing physical performance, cognitive function, mood, sleep, and hormonal balance using validated measures and biomarkers. Results: Ashwagandha supplementation enhanced endurance, strength, and hypertrophy, especially with resistance training. It improved memory, attention, anxiety, and depression, boosted sleep quality, balanced hormones in perimenopause, increased testosterone in men, and aided COVID-19 recovery, all without adverse effects. Conclusion: These findings highlight Ashwagandha's broad-spectrum benefits as a safe and effective therapeutic agent for physical performance, cognitive health, and mental well-being. Further large-scale, long-term studies are needed to refine dosing protocols and expand its clinical applications across diverse populations.
Aim: This study aimed to find out the impact of the various concentrations of ashwagandha plant on biochemical alterations in diabetic rats.Materials and Methods :Thirty adult male albino mice weighing 150±10g, have been utilized & distributed into 2 main groups. The first group (6rats) has been given a basal diet as control (-), the second main group (24 rats) injected with alloxan to cause diabetes, then distributed into four subgroups. One of them was positive diabetes control. Compared to the various three groups, who consumed a basal diet and administered different levels of ashwagandha plant (2.5%, 5%, 7.5%), for 28 days. When the experiment was complete, after treatment with ashwagandha plant, the mice have been weighed & slaughtered, blood samples have been taken, and the serum was separated to do the required measurements. Each FI, BWG & FER were estimated also blood serum glucose, lipide profile, liver function markers, kidney function levels. Results: exhibited that all groups’ values in (HDL-C) showed statistical differences in relation to control (-). While Group 5 was lower value when compared to control (+). Also (ALP)showed groups 5 exhibited statistical variations than control (+). Groups 2 and 3 demonstrated statistical variations than the others.
Ashwagandha (Withania somnifera) is known for its adaptogenic properties, helping the body manage stress from various sources. This review, based on 23 studies, evaluates Ashwagandha's effectiveness in enhancing sleep quality and reducing stress. The herb's bioactive compounds modulate stress responses and neurotransmitter systems, contributing to improved mental and physical resilience. The studies consistently show that Ashwagandha supplementation (250 to 600 mg daily for 4 to 12 weeks) significantly improves sleep quality, latency, and efficiency. These effects are largely due to the modulation of the hypothalamic-pituitary-adrenal (HPA) axis, cortisol reduction, and enhancement of GABAergic and serotonergic pathways. Ashwagandha also extends total sleep time in various populations, including healthy adults and the elderly. In addition to enhancing sleep, Ashwagandha reduces stress by lowering cortisol levels and modulating neurotransmitter systems. Numerous studies highlight its role in alleviating anxiety and improving mental well-being. However, some studies report gastrointestinal issues and potential interactions with medications, necessitating caution and consultation with healthcare providers. This review synthesizes current research, identifies trends, and highlights gaps in the literature, contributing to a better understanding of Ashwagandha's role in modern health practices. Given the challenges of sleep disorders and stress-related conditions, Ashwagandha shows promise as a natural remedy, particularly for those with anxiety or chronic stress. Future research should focus on understanding the underlying mechanisms, ensuring long-term safety, and standardizing supplement quality to strengthen its therapeutic applications.
This chapter investigates the utilization of medicinal plants as a promising avenue for addressing the complex spectrum of mental health disorders, including depression, anxiety, and insomnia. The profound impact of these conditions on human well-being has fueled extensive scientific and clinical interest, prompting a search for innovative therapeutic approaches. Medicinal plants in general provide an abundant supply of bioactive substances with potential pharmacological benefits. Through a narrative exploration of the intricate mechanisms underlying their healing actions, this chapter synthesizes current research findings and ethnopharmcological perspectives to elucidate the role of herbal interventions in ameliorating mental health symptoms. It highlights the necessity for rigorous investigation, including animal studies and randomized clinical investigations, to validate the efficacy of herbal remedies and mitigate challenges associated with generalizations. By advocating for a comprehensive understanding of plant-based interventions and their modulatory effects on neurobiological pathways, this chapter aims to catalyze further research endeavors and therapeutic innovations in harnessing the therapeutic potential of nature’s pharmacopeia for enhancing mental well-being on a global scale.
The recent ban on Ashwagandha (Withania somnifera (L.) Dunal) supplements in Denmark, based on a risk assessment by the Technical University of Denmark (DTU), exemplifies the challenges in regulating traditional herbal medicines within modern frameworks. This article critically examines the DTU report, highlighting methodological flaws including overreliance on animal studies and selective literature review. The report’s disregard for Ashwagandha's long history of traditional use and mischaracterization of its effects, particularly alleged abortifacient properties, contradicts a growing body of scientific evidence supporting its safety and efficacy. The current research demonstrating Ashwagandha's benefits in stress reduction, sleep improvement, and cognitive function further underscores the disparity between scientific findings and the DTU’s conclusions. The ban’s implications extend beyond Denmark, raising questions about regulatory consistency and proportionality in evaluating herbal products globally. The Indian Ministry of Ayush’s critique emphasizes the need for a more comprehensive, evidence-based approach for assessing traditional medicines. This controversy may catalyze the development of integrated evaluation methods, such as the Collaborative Medicine and Science framework, bridging diverse knowledge systems in regulatory decision-making. The case underscores the necessity for a global health paradigm that harmonizes traditional and modern medical approaches, ensuring public safety while preserving access to beneficial traditional remedies.
Objective
Despite the historical neurological use of Withania somnifera, limited evidence supports its efficacy for conditions like anxiety and insomnia. Given its known anti‐stress properties, this review evaluated its safety and efficacy for anxiety and insomnia.
Methods
We searched Medline, Cochrane Library, and Google Scholar until August 2023 for randomized controlled trials (RCTs) comparing W. somnifera to placebo in patients with anxiety and/or insomnia. Outcome measures included changes in anxiety levels via the Hamilton Anxiety Scale (HAM‐A), Sleep Onset Latency (SOL), Total Sleep Time (TST), Wake After Sleep Onset (WASO), Total Time in Bed (TIB), Sleep Efficiency (SE), and Pittsburgh Sleep Quality Index (PSQI) score. We utilized a random‐effect model for pooling Mean Differences (MD) with a 95% Confidence Interval (CI). Heterogeneity was assessed through sensitivity and subgroup analysis, and the quality of RCTs was evaluated using the Cochrane revised risk of bias tool.
Results
Pooled results from five RCTs ( n = 254) demonstrated that W. somnifera significantly reduced HAM‐A scores (MD = −5.96; [95% CI −10.34, −1.59]; P = 0.008; I ² = 98%), as well as sleep parameters such as SOL, TST, PSQI, and SE, but not WASO and TIB.
Conclusion
While W. somnifera extracts yielded promising results, further research with larger sample sizes is needed to confirm its effects on anxiety and insomnia.
Background
Ashwagandha is a well-known Ayurvedic herb used for youthful vigor and wellbeing. This study investigated the effects of 600 mg standardized root extract (>5% withanolides) of Ashwagandha (Withania somnifera) on muscle size, strength and cardiorespiratory endurance following resistance training.
Methods
In this eight-week, parallel-group, multicenter, randomized, double-blind, placebo-controlled clinical study, 80 healthy male and female participants aged 18-45 years, who engaged in regular physical activity were randomly allocated in a 1:1 ratio to receive Ashwagandha (AG, n=40) 300 mg capsules twice daily for eight weeks, or identical placebo (PB, n=40). Seven (3 AG, 4 PB) participants were excluded due to poor compliance. All participants conducted eight-week resistance training. Study outcomes included muscle strength (1RM bench press and leg extension), muscle size (circumference of arm, chest and upper thigh) and cardio-respiratory endurance (VO2max) assessed at baseline and at eight weeks. Analysis of covariance (ANCOVA) was used to estimate adjusted differences based on sex, BMI and chest circumference at baseline.
Results
AG caused greater improvement in bench press (males: p = 0.0084; females: p = 0.0005), leg press (males: p = 0.0049; females: p = 0.018) and endurance (males: p <0.0001; females: p <0.0001) as compared to PB. Also, greater improvements in muscle girth for arm, chest and thigh were seen in both male and female participants with AG. No adverse events were reported in the study.
Conclusions
Eight weeks of AG root extract supplementation along with resistance training is effective in improving muscle strength, growth and endurance in both male and female participants. AG root extract could be a safer, effective and low-cost alternative for athletes to improve muscle endurance.
Lifestyle disorders are types of noncommunicable diseases. A poor and unhealthy lifestyle may initiate a series of interactive disorders that could become fatal (if they go unrecognised and untreated). Several traditional treatment approaches have long been available to treat such diseases. These traditional medical treatments completely rely on herbal medicines. But because of a lack of scientific evidence, these traditional approaches are not recognised by regulatory bodies. Currently, several clinical trials are in progress to look for evidence that might increase their acceptability.
In this chapter, we rely on and examine PubMed sources when discussing the current and potential herbal medications that have recently been or are currently under trial (mostly 2016–2023). The chapter clearly focuses on regulations imposed by the United States’ Federal Drug Administration (FDA). The FDA has currently received more than 800 applications for acceptance, but because these applications lack scientific evidence, most of them are rejected.
Background:
Withania somnifera (WS), a popular medicinal plant of the Solanaceae family, contains active ingredients with antioxidant, anti-inflammatory, immunomodulatory, and anti-stress activities. However, its precise mechanisms of action and optimal use as a supplement are not yet fully understood. The objective of this systematic review is to assess the impact of WS supplementation on cortisol levels in stressed humans by analyzing clinical trials conducted prior to May 2023.
Methods:
The assessment was carried out following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) by exploring the databases of EMBASE, PubMed, Google Scholar, CENTRAL, and Scopus.
Results:
Of the 4788 articles identified, only 9 studies met the selection criteria. The selected studies varied in terms of design, results, formulations, dosages, and treatment duration (30-112 days), and involved subjects with varying degrees of stress. WS supplementation decreases cortisol secretion with no significant adverse effects. Nonetheless, none of the studies evaluated the potential impact of cortisol reduction on adrenal function and long-term effects.
Conclusions:
Brief-term supplementation with WS appears to have a stress-reducing effect in stressed individuals. However, since the long-term effects of WS supplementation are not yet fully understood, WS supplements should be used under medical supervision.
Chronic insomnia disorder (simplified in this document as insomnia) is an increasingly common clinical condition in society and a frequent complaint at the offices of different areas of health practice (particularly Medicine and Psychology). This scenario has been accompanied by a significant evolution in treatment, as well as challenges in approaching patients in an appropriately way. This clinical guideline, coordinated by the Brazilian Sleep Association and the Brazilian Association of Sleep Medicine and counting on the active participation of various specialists in the area, encompasses an update on the diagnosis and treatment of insomnia in adults. To this end, it followed a structured methodology. Topics of interest related to diagnosis were written based on theoretical framework, evidence in the literature, and professional experience. As for the topics related to the treatment of insomnia, a series of questions were developed based on the PICO acronym (P – Patient, problem, or population; I – Intervention; C – Comparison, control, or comparator; O – Outcome). The work groups defined the eligible options within each of these parameters. Regarding pharmacological interventions, only the ones currently available in Brazil or possibly becoming available in the upcoming years were considered eligible. Systematic reviews were conducted to help prepare the texts and define the level of evidence for each intervention. The final result is an objective and practical document providing recommendations with the best scientific support available to professionals involved in the management of insomnia.
Background
The Coronavirus disease (COVID-19) impacted not only physical health but also psychological health, including anxiety, depressive symptoms, and sleep issues. Disrupted sleep has now become a global concern and burden in the post-COVID period of recovery. The Unani system of medicine elaborated on sleeping issues and their management during the pandemic. However, the claims of the Unani system and its medications in improving the various domains of sleep quality during the revival period have not been investigated.
Materials and methods
A search of electronic databases on Pub Med, Scopus, Web of Science, and CINAHL, on sleep disorders, post-COVID-19 and a manual search of Unani classical text related to sleep quality improvement methods was conducted.
Results
Recent scientific evidence has found a positive association between COVID-19 and sleep disorders. Unani medicine suggests improvement of sleep issues by maintaining six essential factors, dieto-therapy, pharmacotherapy, and regimens (like Nutool (irrigation), Hamam (Turkish bath), and Dalk (massage). Several pre-clinical and clinical trials done on Unani herbs (single and poly-herbal preparations) have elucidated the scientific rationale for improving sleep quality.
Conclusion
Unani therapy has sufficient potential for improving sleep outcomes for COVID-19 patients as they are efficacious, safe and affordable therapeutic options. Additionally, there is still a need for evidence to support the validity of Unani psychotherapy as a multifaceted and holistic approach.
Cancer is amenable to low-cost treatments, given that it has a significant metabolic component, which can be affected through diet and lifestyle change at minimal cost. The Warburg hypothesis states that cancer cells have an altered cell metabolism towards anaerobic glycolysis. Given this metabolic reprogramming in cancer cells, it is possible to target cancers metabolically by depriving them of glucose. In addition to dietary and lifestyle modifications which work on tumors metabolically, there are a panoply of nutritional supplements and repurposed drugs associated with cancer prevention and better treatment outcomes. These interventions and their evidentiary basis are covered in the latter half of this review to guide future cancer treatment.
Withania somnifera (Ashwagandha) is one of the most renowned and revered medicinal plants in the Indian Ayurvedic system of medicine. Ashwagandha Rasayanas (tonics), capsules, tablets, and powdered herbs (churna) have been used for curing a wide variety of ailments, including reproductive problems, and for improving fertility in men and women as well as erectile dysfunction (ED) in men. Iron accumulation in reproductive organs is caused by excessive dietary intake of iron, dysregulation of iron transporters, chronic blood transfusions, and hemochromatosis. Iron overload produces oxidative stress and causes atrophy of ovaries and testes and hypogonadism, which leads to infertility in men and women. Emerging evidence from preclinical and clinical studies suggests that excessive iron-induced infertility results from dysfunction of the hypothalamic-pituitary-gonadal axis and consequently perturbs the secretion of sex hormones (GnRH, FSH, LH, estrogen, progesterone, and testosterone). The focus of this review is to summarize the pathophysiology of iron-overload toxicity of reproductive organs and the reversal of male/female infertility and libido with Ashwagandha. The bioactive ingredients of Ashwagandha appear to restore iron–overload infertility by acting on iron chelation and capturing iron free radicals (Fe+++) produced by the Fenton reaction. Many synthetic drugs have been tried for treating iron overload infertility, but the outcome has been inconsistent. Considering the high cost of these drugs, Ashwagandha may be a safer and more costeffective phytomedicine to cure iron-overload infertility and enhance libido in humans. Collectively, the iron chelation and antioxidant effects of Ashwagandha seem to reverse iron-overload infertility in men and women by improving testicular and ovarian functions.
Withania somnifera (L.) Dunal, abundant in the Indian subcontinent as Ashwagandha or winter cherry, is a herb of unprecedented therapeutic value. The number of ailments for which crude Ashwagandha extract can be used as a preventive or curative is practically limitless; and this explains why its use has been in vogue in ancient Ayurveda since at-least about four thousand years. The therapeutic potential of Ashwagandha mainly owes from its reservoir of alkaloids (isopelletierine, anaferine), steroidal lactones (withanolides) and saponins with an extra acyl group (sitoindoside VII and VIII). Withaferin A is an exceptionally potent withanolide which is found in high concentrations in W. somnifera plant extracts. The high reactivity of Withaferin A owes to the presence of a C-28 ergostane network with multiple sites of unsaturation and differential oxygenation. It interacts with the effectors of multiple signaling pathways involved in inflammatory response, oxidative stress response, cell cycle regulation and synaptic transmission and has been found to be significantly effective in inducing programmed cell death in cancer cells, restoring cognitive health, managing diabetes, alleviating metabolic disorders, and rejuvenating the overall body homeostasis. Additionally, recent studies suggest that Withaferin A (WA) has the potential to prevent viral endocytosis by sequestering TMPRSS2, the host transmembrane protease, without altering ACE-2 expression. The scope of performing subtle structural modifications in this multi-ring compound is believed to further expand its pharmacotherapeutic horizon. Very recently, a novel, heavy metal and pesticide free formulation of Ashwagandha whole herb extract, with a significant amount of WA, termed W-ferinAmax, has been developed. The present review attempts to fathom the present and future of this wonder molecule with comprehensive discussion on its therapeutic potential, safety and toxicity.Key teaching pointsWithania somnifera (L.) Dunal is a medicinal plant with versatile therapeutic values.The therapeutic potential of the plant owes to the presence of withanolides such as Withaferin A.Withaferin A is a C-28 ergostane based triterpenoid with multiple reactive sites of therapeutic potential.It is effective against a broad spectrum of ailments including neurodegenerative disorders, cancer, inflammatory and oxidative stress disorders and it also promotes cardiovascular and sexual health.W-ferinAmax Ashwagandha, is a heavy metal and pesticide free Ashwagandha whole herb extract based formulation with significant amount of Withaferin A.
Background : Ashwagandha is a well-known Ayurvedic herb used for youthful vigor and wellbeing. This study investigated the effects of 300 mg standardized root extract (>5% withanolides) of Ashwagandha ( Withania somnifera ) on muscle mass, strength and cardiorespiratory endurance following resistance training.
Methods: In this eight-week, parallel-group, multicenter, randomized, double-blind, placebo-controlled clinical study, 80 healthy male and female participants aged 18-45 years, who engaged in regular physical activity were randomly allocated in a 1:1 ratio to receive Ashwagandha (AG, n=40) 300 mg capsules twice daily for eight weeks, or identical placebo (PB, n=40). Seven (3 AG, 4 PB) participants were excluded due to poor compliance. All participants conducted eight-week resistance training. Study outcomes included muscle strength (1RM bench press and leg extension), muscle size (circumference of arm, chest and upper thigh) and cardio-respiratory endurance (VO 2max ) assessed at baseline and at eight weeks. Analysis of covariance (ANCOVA) was used to estimate adjusted differences based on sex, BMI and chest circumference at baseline.
Results: AG caused greater improvement in chest press (males: p = 0.0084; females: p = 0.0005), leg press (males: p = 0.0049; females: p = 0.018) and endurance (males: p <0.0001; females: p <0.0001) as compared to PB. Also, greater improvements in muscle girth for arm, chest and thigh were seen in both male and female participants with AG. No adverse events were reported in the study.
Conclusions: Eight weeks of AG root extract supplementation along with resistance training is effective in improving muscle strength, growth, endurance and recovery in both male and female participants. AG root extract could be a safer, effective and low-cost alternative for athletes to improve muscle endurance.
The incidence and prevalence of age‐related neurodegenerative dementias have been increasing. There is no curative therapy and conventional drug treatment can cause problems for patients. Medicinal plants traditionally used for problems associated with ageing are emerging as a therapeutic resource. The main aim is to give a proposal for use and future research based on scientific knowledge and tradition. A literature search was conducted in several searchable databases. The keywords used were related to neurodegenerative dementias, ageing and medicinal plants. Boolean operators and filters were used to focus the search. As a result, there is current clinical and preclinical scientific information on 49 species used in traditional medicine for ageing‐related problems, including neurodegenerative dementias. There are preclinical and clinical scientific evidences on their properties against protein aggregates in the central nervous system and their effects on neuroinflammation, apoptosis dysregulation, mitochondrial dysfunction, gabaergic, glutamatergic and dopaminergic systems alterations, monoamine oxidase alterations, serotonin depletion and oestrogenic protection. In conclusion, the potential therapeutic effect of the different medicinal plants depends on the type of neurodegenerative dementia and its stage of development, but more clinical and preclinical research is needed to find better, safer and more effective treatments.
The herb ashwagandha (Withania somnifera) is a member of the nightshade family. It has been used as a nervine tonic in Ayurveda since around 3000 BC. It is an adaptogen that helps maintain homeostasis of the body during stress. It also has antiinflammatory, antiarthritic, and antineuralgic effects. Ashwagandha can be beneficial for numerous diseases and conditions, including hyperlipidemia, diabetes, female sexual dysfunction, male infertility, osteoarthritis, cognitive impairment due to Alzheimer’s disease, anxiety, and much more. This chapter examines some of the scientific research conducted on ashwagandha, both alone and in combination formulas, for treating numerous health conditions. It summarizes results from several human studies of the herb’s use in treating cardiometabolic, musculoskeletal, neurological, psychiatric, and endocrine disorders. Finally, the chapter presents a list of ashwagandha’s Active Constituents, different Commonly Used Preparations and Dosage, and a Section on “Safety and Precaution” that examines side effects, toxicity, and disease and drug interactions.
Withanolide derivatives have anticancer, anti-inflammatory, and other functions and are components of Indian traditional Ayurvedic medicine. Here, we found that 2,3-dihydro-3β-methoxy withaferin-A (3βmWi-A), a derivative of withaferin-A (Wi-A) belonging to a class of withanolides that are abundant in Ashwagandha (Withania somnifera), lengthened the period of the circadian clock. This compound dose-dependently elongated circadian rhythms in Sarcoma 180 cancer cells and in normal fibroblasts including NIH3T3 and spontaneously immortalized mouse embryonic fibroblasts (MEF). Furthermore, 3βmWi-A dose-dependently upregulated the mRNA expression and promoter activities of Bmal1 after dexamethasone stimulation and of the nuclear orphan receptors, Rora and Nr1d1, that comprise the stabilization loop for Bmal1 oscillatory expression. We showed that 3βmWi-A functions as an inverse agonist for RORa with an IC50 of 11.3 μM and that 3βmWi-A directly, but weakly, interacts with RORa (estimated dissociation constant [Kd], 5.9 μM). We propose that 3βmWi-A is a novel modulator of circadian rhythms.
Introduction
Insomnia is a prevalent sleep disorder that can profoundly impact a person’s physical health and mental wellbeing. Most of the currently available drugs for insomnia exert adverse effects. Hence, alternative herbal therapies could be effective in treating insomnia. Ashwagandha, a proven “Rasayana” from ancient Ayurveda is having the required potential to treat insomnia.
Objective
To determine the efficacy and safety of Ashwagandha root extract in patients with insomnia and anxiety.
Methods
This was a randomized, double-blind, placebo-controlled study conducted at Prakruti Hospital, Kalwa, Maharashtra, India. A total of 60 patients were randomly divided into two groups: test (n = 40) and placebo (n = 20) in a randomization ratio of 2:1. Test product was a capsule containing highest concentration full-spectrum Ashwagandha root extract 300 mg, and the placebo was an identical capsule containing starch. Both treatments were given twice daily with milk or water for 10 weeks. Sleep actigraphy (Respironics Philips) was used for assessment of sleep onset latency (SOL), total sleep time (TST), sleep efficiency (SE) and wake after sleep onset (WASO). Other assessments were total time in bed (sleep log), mental alertness on rising, sleep quality, Pittsburgh Sleep Quality Index (PSQI), and Hamilton Anxiety Rating Scale (HAM-A) scales.
Results
Two patients, one from each group, did not complete study and the per-protocol dataset (n = 58) included 29 and 19 patients from test and placebo, respectively. The baseline parameters were similar in the two groups at baseline. The sleep onset latency was improved in both test and placebo at five and 10 weeks. However, the SOL was significantly shorter (p, 0.019) after 10 weeks with test [29.00 (7.14)] compared to placebo [33.94 (7.65)]. Also, significant improvement in SE scores was observed with Ashwagandha which was 75.63 (2.70) for test at the baseline and increased to 83.48 (2.83) after 10 weeks, whereas for placebo the SE scores changed from 75.14 (3.73) at baseline to 79.68 (3.59) after 10 weeks. Similarly, significant improvement in sleep quality was observed with test compared to placebo (p, 0.002). Significant improvement was observed in all other sleep parameters, i.e., SOL, SE, PSQI and anxiety (HAM-A scores) with Ashwagandha root extract treatment for 10 weeks.
Conclusion
Ashwagandha root extract is a natural compound with sleep-inducing potential, well tolerated and improves sleep quality and sleep onset latency in patients with insomnia at a dose of 300 mg extract twice daily. It could be of potential use to improve sleep parameters in patients with insomnia and anxiety, but need further large-scale studies.
Background:
The National Institutes of Health estimates the prevalence of insomnia in menopausal women at 40-50%. Some studies have shown that acupuncture might be effective in treating primary insomnia and insomnia related to depression and stroke. Although there are some programs supporting insomnia during the menopausal transition, there are few randomized controlled trials (RCT) to provide evidence regarding their effectiveness. We design a RCT of suitable sample size to verify the effectiveness of acupuncture in patients with insomnia during the menopausal transition and to form an optimized acupuncture treatment protocol.
Method/design:
In this randomized, single-site, single-blind, placebo-controlled trial, 84 eligible patients will be recruited and randomly assigned to either the acupuncture group (n = 42) or the sham control group (n = 42) in a 1:1 ratio. Participants will receive a total of 18 treatment sessions for eight consecutive weeks. Treatments will be given three times per week in the first four weeks, twice a week for the next two weeks, and finally once weekly for the final two weeks. Treatment will utilize eight main acupoints (GV20, GV24, GV29, RN6, RN4, SP6, HT7, EX-HN22) and extra two acupoints based on syndrome differentiation. The primary outcome will be assessed using the Pittsburgh Sleep Quality Index (PSQI). The secondary outcomes will be measured by sleep parameters recorded in the Actigraphy (SE, TST, SA), Insomnia Severity Index (ISI), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Menopause Quality of Life (Men-QOL). The primary outcomes will be assessed at baseline, week 4, week 8, and the first and third month after the end of treatment.
Discussion:
If the results confirm that acupuncture is effective and safe for the treatment on insomnia in menopausal women, this positive outcome could provide evidence for clinical application.
Trial registration:
Chinese Clinical Trial Registry, ChiCTR1800018645 . Registered on 10 January 2018.
Introduction:
The purpose of this systematic review is to provide supporting evidence for a clinical practice guideline on the use of actigraphy.
Methods:
The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine. A systematic review was conducted to identify studies that compared the use of actigraphy, sleep logs, and/or polysomnography. Statistical analyses were performed to determine the clinical significance of using actigraphy as an objective measure of sleep and circadian parameters. Finally, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence for making recommendations.
Results:
The literature search resulted in 81 studies that met inclusion criteria; all 81 studies provided data suitable for statistical analyses. These data demonstrate that actigraphy provides consistent objective data that is often unique from patient-reported sleep logs for some sleep parameters in adult and pediatric patients with suspected or diagnosed insomnia, circadian rhythm sleep-wake disorders, sleep-disordered breathing, central disorders of hypersomnolence, and adults with insufficient sleep syndrome. These data also demonstrate that actigraphy is not a reliable measure of periodic limb movements in adult and pediatric patients. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations.
This study aimed to investigate the association between sleeping pill use and hypertension or blood pressure (BP) via a cross-sectional analysis.
A total of 11,225 subjects (5875 men and 5350 women) underwent health examinations. We compared the proportion of sleeping pill users among hypertension (n = 5099) and normotensive (n = 6126) participants. We analyzed participants with no intake of antihypertensive medication (n = 7788), comparing the proportions with high systolic BP (SBP) ≥140, high diastolic BP (DBP) ≥90, and high pulse pressure (PP) ≥50 mm Hg across 3 subgroups. These groups were classified according to the sleeping pill use [nonuse group (n = 6869); low-frequency-use group, defined as taking sleeping pills ≤2 days per week (n = 344); and high-frequency-use group, defined as taking sleeping pills ≥3 days per week (n = 575)].
In the multivariable-adjusted model, odds of sleeping pill use (odds ratio (OR), 1.14; P < .05) was significantly higher in the hypertensive group compared with the normotensive group. In participants with no intake of antihypertensive medication, odds of high SBP (OR, 0.65; P < .0005), high DBP (OR, 0.58; P < .005), and high PP (OR, 0.77; P < .01) were significantly lower in the high-frequency-use group compared with the nonuse group. Odds of high DBP (OR, 0.59; P < .05) was significantly lower in the low-frequency-use group.
Sleeping pills were more frequently required in hypertensive participants than in the normotensive ones. Sleeping pill use may decrease BP and assist in the treatment of high BP in patients with sleep disturbances.
The goal of this study is to examine the effects of aromatherapy massage on sleep quality of nurses with monthly rotating night shifts. Subjects were enrolled at a medical center in central Taiwan with overall score ≥ 5 of Pittsburgh Sleep Quality Index (PSQI) and randomly assigned to the treatment or control groups. They were validated by pretests during their first graveyard shift in the trial period and the sleep quality information was collected by using the PSQI and sleep detectors. During the second graveyard shift, the treatment group received aromatherapy massage and the control group rested in the same aromatherapy room after work. All subjects filled out the PSQI surveys and the sleep quality information was collected during massage or resting and the following night. We found that the total PSQI was significantly decreased in the treatment group following the aromatherapy massage. Specifically, the components such as subjective sleep quality, sleep disturbance, and daytime dysfunction were significantly decreased. However, there were no significant changes of average PSQI scores between the two groups before and after intervention. Taken together, our study suggested that aromatherapy massage could improve sleep quality of nurses with monthly rotating night shift.
Chronic stress has been associated with a number of illnesses, including obesity. Ashwagandha is a well-known adaptogen and known for reducing stress and anxiety in humans. The objective of this study was to evaluate the safety and efficacy of a standardized root extract of Ashwagandha through a double-blind, randomized, placebo-controlled trial. A total of 52 subjects under chronic stress received either Ashwagandha (300 mg) or placebo twice daily. Primary efficacy measures were Perceived Stress Scale and Food Cravings Questionnaire. Secondary efficacy measures were Oxford Happiness Questionnaire, Three-Factor Eating Questionnaire, serum cortisol, body weight, and body mass index. Each subject was assessed at the start and at 4 and 8 weeks. The treatment with Ashwagandha resulted in significant improvements in primary and secondary measures. Also, the extract was found to be safe and tolerable. The outcome of this study suggests that Ashwagandha root extract can be used for body weight management in adults under chronic stress.
Although insomnia is, by far, the most commonly encountered sleep disorder in medical practice, our knowledge in regard to its neurobiology and medical significance is limited. Activation of the hypothalamic-pituitary-adrenal axis leads to arousal and sleeplessness in animals and humans; however, there is a paucity of data regarding the activity of the hypothalamic-pituitary-adrenal axis in insomniacs. We hypothesized that chronic insomnia is associated with increased plasma levels of ACTH and cortisol. Eleven young insomniacs (6 men and 5 women) and 13 healthy controls (9 men and 4 women) without sleep disturbances, matched for age and body mass index, were monitored in the sleep laboratory for 4 consecutive nights, whereas serial 24-h plasma measures of ACTH and cortisol were obtained during the fourth day. Insomniacs, compared with controls, slept poorly (significantly higher sleep latency and wake during baseline nights). The 24-h ACTH and cortisol secretions were significantly higher in insomniacs, compared with normal controls (4.2 +/- 0.3 vs. 3.3 +/- 0.3 pM, P = 0.04; and 218.0 +/- 11.0 vs. 190.4 +/- 8.3 nM, P = 0.07). Within the 24-h period, the greatest elevations were observed in the evening and first half of the night. Also, insomniacs with a high degree of objective sleep disturbance (% sleep time < 70), compared with those with a low degree of sleep disturbance, secreted a higher amount of cortisol. Pulsatile analysis revealed a significantly higher number of peaks per 24 h in insomniacs than in controls (P < 0.05), whereas cosinor analysis showed no differences in the temporal pattern of ACTH or cortisol secretion between insomniacs and controls. We conclude that insomnia is associated with an overall increase of ACTH and cortisol secretion, which, however, retains a normal circadian pattern. These findings are consistent with a disorder of central nervous system hyperarousal rather than one of sleep loss, which is usually associated with no change or decrease in cortisol secretion or a circadian disturbance. Chronic activation of the hypothalamic-pituitary-adrenal axis in insomnia suggests that insomniacs are at risk not only for mental disorders, i.e. chronic anxiety and depression, but also for significant medical morbidity associated with such activation. The therapeutic goal in insomnia should be to decrease the overall level of physiologic and emotional arousal, and not just to improve the nighttime sleep.
Introduction:
Ashwagandha (Withania somnifera [L.] Dunal) has been traditionally used for various actions ranging from vitalizer, improve endurance and stamina, promote longevity, improve immunity, and male and female fertility. However, clinical studies are needed to prove the clinical efficacy of this herb, especially in cardiovascular endurance and physical performance.
Aims:
This prospective, double-blind, randomized, and placebo-controlled study evaluated the efficacy of Ashwagandha roots extract in enhancing cardiorespiratory endurance and improving the quality of life (QOL) in 50 healthy male/female athletic adults.
Materials and methods:
Cardiorespiratory endurance was assessed by measuring the oxygen consumption at peak physical exertion (VO2 max) levels during a 20 m shuttle run test. The World Health Organization self-reported QOL questionnaire (physical health, psychological health, social relationships, and environmental factors) was used to assess the QOL. Student's t-test was used to compare the differences in a mean and change from baseline VO2 max levels, whereas Wilcoxon signed-rank test was used to assess changes in QOL scores from baseline in the two groups.
Results:
There was a greater increase from baseline (P < 0.0001) in the mean VO2 max with KSM-66 Ashwagandha (n = 24) compared to placebo (n = 25) at 8 weeks (4.91 and 1.42, respectively) and at 12 weeks (5.67 and 1.86 respectively). The QOL scores for all subdomains significantly improved to a greater extent in the Ashwagandha group at 12 weeks compared to placebo (P < 0.05).
Conclusion:
The findings suggest that Ashwagandha root extract enhances the cardiorespiratory endurance and improves QOL in healthy athletic adults.
Background. Many women experience sexual dysfunction where there are orgasm disorders and sexual difficulties. Ashwagandha (Withania somnifera) is a herb known to improve the body's physical and psychological condition. Objective. The purpose of the study was to determine the efficacy and safety of a high-concentration ashwagandha root extract (HCARE) supplementation for improving sexual function in healthy females. Methods. In this pilot study, 50 study subjects were randomized to either (i) HCARE-treated group or (ii) placebo-(starch-) treated group. The subjects consumed either HCARE or placebo capsules of 300mg twice daily for 8 weeks. Sexual function was assessed using two psychometric scales, the Female Sexual Function Index (FSFI) Questionnaire and the Female Sexual Distress Scale (FSDS), and by the number of total and successful sexual encounters. Results. The analysis indicates that treatment with HCARE leads to significantly higher improvement, relative to placebo, in the FSFI Total score (í µí± < 0.001), FSFI domain score for " arousal " (í µí± < 0.001), " lubrication " (í µí± < 0.001), " orgasm " (í µí± = 0.004), and " satisfaction " (í µí± < 0.001), and also FSDS score (í µí± < 0.001) and the number of successful sexual encounters (í µí± < 0.001) at the end of the treatment. Conclusions. This study demonstrated that oral administration of HCARE may improve sexual function in healthy women. The present study is registered in the Clinical Trial Registry, Government of India, with a number CTRI/2015/07/006045.
Work in animals and humans has suggested the existence of a slow wave sleep (SWS)-promoting/electroencephalogram (EEG)-synchronizing center in the mammalian lower brainstem. Although sleep-active GABAergic neurons in the medullary parafacial zone (PZ) are needed for normal SWS, it remains unclear whether these neurons can initiate and maintain SWS or EEG slow-wave activity (SWA) in behaving mice. We used genetically targeted activation and optogenetically based mapping to examine the downstream circuitry engaged by SWS-promoting PZ neurons, and we found that this circuit uniquely and potently initiated SWS and EEG SWA, regardless of the time of day. PZ neurons monosynaptically innervated and released synaptic GABA onto parabrachial neurons, which in turn projected to and released synaptic glutamate onto cortically projecting neurons of the magnocellular basal forebrain; thus, there is a circuit substrate through which GABAergic PZ neurons can potently trigger SWS and modulate the cortical EEG.
Withania somnifera is a medicinal plant extends over a large area, from the Atlantic ocean to South East Asia and from the Mediterranean region to
South Africa. The medicinal plants are widely used by the traditional medical practitioners for curing various diseases in their day to day practice. In
traditional systems of medicine, different parts (leaves, stem, flower, root, seeds, bark and even whole plant) of Withania somnifera (known as
Ashwagandha in Hindi), a small herb seen throughout India, have been recommended for the treatment of aphrodisiac, liver tonic, antinflammatory agent, astringent, and more recently to treat bronchitis, asthma, ulcers, emaciation, insomnia, and senile dementia etc. Clinical trials
and animal research support the therapeutic use of ashwaganda for anxiety, cognitive and neurological disorders, inflammation, and Parkinson’s
disease. Ashwaganda’s chemopreventive properties make it a potentially useful adjunct for the patients undergoing radiation and chemotherapy.
Ashwaganda is also used therapeutically as an adaptogen for patients with nervous exhaustion, insomnia, and debility due to stress, and as an
immune stimulant in patients with low white blood cell counts in blood. The major biochemical constituents of ashwaganda root are steroidal
alkaloids and steroidal lactones in a class of constituents called withanolides.
Ashwagandha (Withania somnifera) has been described in traditional Indian Ayurvedic medicine as an aphrodisiac that can be used to treat male sexual dysfunction and infertility. This pilot study was conducted to evaluate the spermatogenic activity of Ashwagandha root extract in oligospermic patients. Forty-six male patients with oligospermia (sperm count < 20 million/mL semen) were enrolled and randomized either to treatment (n = 21) with a full-spectrum root extract of Ashwagandha (675 mg/d in three doses for 90 days) or to placebo (n = 25) in the same protocol. Semen parameters and serum hormone levels were estimated at the end of 90-day treatment. There was a 167% increase in sperm count (9.59 ± 4.37 × 10(6)/mL to 25.61 ± 8.6 × 10(6)/mL; P < 0.0001), 53% increase in semen volume (1.74 ± 0.58 mL to 2.76 ± 0.60 mL; P < 0.0001), and 57% increase in sperm motility (18.62 ± 6.11% to 29.19 ± 6.31%; P < 0.0001) on day 90 from baseline. The improvement in these parameters was minimal in the placebo-treated group. Furthermore, a significantly greater improvement and regulation were observed in serum hormone levels with the Ashwagandha treatment as compared to the placebo. The present study adds to the evidence on the therapeutic value of Ashwagandha (Withania somnifera), as attributed in Ayurveda for the treatment of oligospermia leading to infertility.
Sleep disturbances and decline in the physical functionality are common conditions associated with aging. Pharmacological treatment of sleep disturbances can be associated with various adverse effects. Short term trials of Yoga on sleep have shown beneficial effects.
To evaluate the effect of long-term Yoga exercises on sleep quality and quality of life (QOL) in the elderly.
This was a cross-sectional study in which data were collected from elderly people aged 60 years or more living in Nagpur city. We employed two types of survey questionnaires: Pittsburgh sleep quality index (PSQI) and QOL Leiden-Padua (LEIPAD) Questionnaire. A total of 65 elderly men and women who signed an informed consent and completed questionnaires were included in the study. Sleep quality score PSQI and QOL (LEIPAD Questionnaire) score of the study group were evaluated and compared with the control group using Mann-Whitney U test.
Total PSQI score in Yoga group was lower than that of the control group. Also various QOL scores of the Yoga groups were higher than the control group.
Addition of regular Yoga exercises in the daily routine of elderly people can help to achieve good sleep quality as well as improve the QOL.
Context:
Stress is a state of mental or emotional strain or tension, which can lead to underperformance and adverse clinical conditions. Adaptogens are herbs that help in combating stress. Ayurvedic classical texts, animal studies and clinical studies describe Ashwagandha as a safe and effective adaptogen.
Aims:
The aim of the study was to evaluate the safety and efficacy of a high-concentration full-spectrum extract of Ashwagandha roots in reducing stress and anxiety and in improving the general well-being of adults who were under stress.
Settings and design:
Single center, prospective, double-blind, randomized, placebo-controlled trial.
Materials and methods:
A total of 64 subjects with a history of chronic stress were enrolled into the study after performing relevant clinical examinations and laboratory tests. These included a measurement of serum cortisol, and assessing their scores on standard stress-assessment questionnaires. They were randomized to either the placebo control group or the study drug treatment group, and were asked to take one capsule twice a day for a period of 60 days. In the study drug treatment group, each capsule contained 300 mg of high-concentration full-spectrum extract from the root of the Ashwagandha plant. During the treatment period (on Day 15, Day 30 and Day 45), a follow-up telephone call was made to all subjects to check for treatment compliance and to note any adverse reactions. Final safety and efficacy assessments were done on Day 60.
Statistical analysis:
t-test, Mann-Whitney test.
Results:
The treatment group that was given the high-concentration full-spectrum Ashwagandha root extract exhibited a significant reduction (P<0.0001) in scores on all the stress-assessment scales on Day 60, relative to the placebo group. The serum cortisol levels were substantially reduced (P=0.0006) in the Ashwagandha group, relative to the placebo group. The adverse effects were mild in nature and were comparable in both the groups. No serious adverse events were reported.
Conclusion:
The findings of this study suggest that a high-concentration full-spectrum Ashwagandha root extract safely and effectively improves an individual's resistance towards stress and thereby improves self-assessed quality of life.
Cycling is an endurance sport relying mainly on aerobic capacity to provide fuel during long-duration cycling events. Athletes are constantly searching for new methods to improve this capacity through various nutritional and ergogenic aids.s
The aim of the study was to find out the effect of Ashwagandha on the cardiorespiratory endurance capacity, that is, aerobic capacity of elite Indian cyclists.
Forty elite (elite here refers to the participation of the athlete in at least state-level events) Indian cyclists were chosen randomly and were equally divided into experimental and placebo groups. The experimental group received 500 mg capsules of aqueous roots of Ashwagandha twice daily for eight weeks, whereas the placebo group received starch capsules.
The baseline treadmill test for the cyclists were performed to measure their aerobic capacity in terms of maximal aerobic capacity (VO(2) max), metabolic equivalent, respiratory exchange ratio (RER), and total time for the athlete to reach his exhaustion stage. After eight weeks of supplementation, the treadmill test was again performed and results were obtained.
There was significant improvement in the experimental group in all parameters, whereas the placebo group did not show any change with respect to their baseline parameters. There was significant improvement in the experimental group in all parameters, namely, VO(2) max (t = 5.356; P < 0.001), METS (t = 4.483; P < 0.001), and time for exhaustion on treadmill (t = 4.813; P < 0.001) in comparison to the placebo group which did not show any change with respect to their baseline parameters.
Ashwagandha improved the cardiorespiratory endurance of the elite athletes.
The objective of the present study was to evaluate the antidepressant action of Withania somnifera (WS) as well as its interaction with the conventional antidepressant drugs and to delineate the possible mechanism of its antidepressant action using forced swimming model in mice. Effect of different doses of WS, fluoxetine and imipramine were studied on forced swimming test induced mean immobility time (MIT). Moreover effect of WS 100 mg/kg, i.p. was observed at different time intervals. Effect produced by combination of sub therapeutic doses of WS with imipramine (2.5 mg/kg, i.p.) as well as fluoxetine (2.5 mg/kg, i.p.) were also observed. Effect of WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) were observed in mice pretreated with reserpine (2 mg/kg, i.p.) and clonidine (0.15 mg/kg, i.p.). Effects of prazosin (3 mg/kg, i.p.) or haloperidol (0.1 mg/kg, i.p.) pre-treatment were also observed on WS induced decrease in MIT. WS produced dose dependent decrease in MIT. Maximum effect in MIT was observed after 30 min of treatment with WS 100 mg/kg, i.p. Combination of WS (37.5 mg/kg, i.p.) with imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) also produced significant decrease in the MIT. Clonidine and reserpine induced increase in MIT, was significantly reversed by treatment with WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.). Pre-treatment with prazosin but not haloperidol, significantly antagonized the WS (100 mg/kg, i.p.) induced decrease in MIT. It is concluded that, WS produced significant decrease in MIT in mice which could be mediated partly through a adrenoceptor as well as alteration in the level of central biogenic amines.
Sleep deprivation disrupts significantly sleep pattern and cause poor quality of sleep. The aim the present study was to explore role of Withania somniferra root extract in sleep-disturbed rats. Male wistar rats (n=5-6/group) were sleep deprived for 24 h using grid suspended over water method. Withania somniferra extract (100 mg/kg) was administered intraperitoneally (i.p.) 30 min before actual recording (EEG and EMG) recording and electrophysiological recordings are further classified as- sleep latency, slow wave sleep, paradoxical sleep, total sleep, wakefulness. One day (24 h) sleep deprivation delayed latency sleep, reduced duration of slow wave sleep, rapid eye movement sleep, total sleep time and increased total waking as compared to animals placed on saw dust (P<0.05). Pretreatment with Withania somniferra extract (100 mg/kg) and diazepam (0.5 mg/kg) significantly improved electrophysiological parameters, which was further reversed by picrotoxin (2 mg/kg) and potentiated by muscimol (0.05 mg/kg). Flumazenil (2 mg/kg) did not produce any significant effect on the sleep parameters of Withania somnifera root extract. Present study suggests the involvement of GABAergic mechanism in the sleep promoting effect of Withania somniferra in sleep-disturbed state.
Several medicinal plants have been described to be beneficial for cardiac ailments in Ayurveda like Ashwagandha and Arjuna. Ashwagandha-categorised as Rasayanas, and described to promote health and longevity and Arjuna primarily for heart ailments. coronary artery disease, heart failure, hypercholesterolemia, anginal pain and can be considered as a useful drug for coronary artery disease, hypertension and ischemic cardiomyopathy.
There are no scientific clinical studies showing effect of both these drugs on exercise performance after regular administration when given as supplements The present study was therefore designed and performed to assess the effects of Withania somnifera (Ashwagandha) and Terminalia arjuna (Arjuna) individually and as a combination on maximum velocity, average absolute and relative Power, balance, maximum oxygen consumption (VO2 max) and blood pressure in humans.
Forty normal healthy. Subjects (either sex, mean age 20.6 ± 2.5yrs and mean Body Mass Index 21.9 ± 2.2) were recruited after written informed consent was obtained. Institutional Ethics Committee permission was also obtained. Thirty participants were assigned to experimental group of which 10 received standardized root extracts of Withania somnifera, 10 received standardized bark extract of Terminalia arjuna and the rest of the 10 received standardized root extract of Withania somnifera in addition to bark extract of Terminalia arjuna both. Both the drugs were given in the form of capsules (dosage 500mg/day for both the drugs). Ten participants received placebo (capsules filled with flour). All the subjects continued the regimen for 8 weeks. All variables were assessed before and after the course of drug administration
Our study showed that Withania somnifera increased velocity, power and VO2 max whereas Terminalia arjuna increased VO2 max and lowered resting systolic blood pressure. When given in combination, the improvement was seen in all parameters except balance and diastolic blood pressure.
Withania somnifera may therefore be useful for generalized weakness and to improve speed and lower limb muscular strength and neuro-muscular co-ordination. Terminalia arjuna may prove useful to improve cardio-vascular endurance and lowering systolic blood pressure. Both drugs appear to be safe for young adults when given for mentioned dosage and duration.
Insomnia is a disorder characterized by inability to sleep or a total lack of sleep, prevalence of which ranges from 10 to 15% among the general population with increased rates seen among older ages, female gender, White population and presence of medical or psychiatric illness. Yet this condition is still under-recognized, under-diagnosed, and under-treated. This article aims to review the operational definitions and management of chronic insomnia. A computerized search on PubMed carried from 1980 to January 2009 led to the summarization of the results. There are several strategies to manage chronic insomnia. To initiate treatment, it is necessary to define it and differentiate it from other co-morbid psychiatric disorders. Non-pharmacologic strategies such as stimulus control therapy and relaxation and cognitive therapies have the best effect sizes followed by sleep restriction, paradoxical intention and sleep hygiene education which have modest to less than modest effect sizes. Among pharmacotherapeutic agents, non-benzodiazepine hypnotics are the first line of management followed by benzodiazepines, amitryptiline and antihistaminics. However, adequate trials of combined behavior therapy and pharmacotherapy are the best course of management.
Since the discovery of rapid eye movement (REM) sleep (also known as paradoxical sleep; PS), it is accepted that sleep is an active process. PS is characterized by EEG rhythmic activity resembling that of waking with a disappearance of muscle tone and the occurrence of REMs, in contrast to slow-wave sleep (SWS, also known as non-REM sleep) identified by the presence of delta waves. Here, we review the most recent data on the mechanisms responsible for the genesis of SWS and PS. Based on these data, we propose an updated integrated model of the mechanisms responsible for the sleep-wake cycle. This model introduces for the first time the notion that the entrance and exit of PS are induced by different mechanisms. We hypothesize that the entrance from SWS to PS is due to the intrinsic activation of PS-active GABAergic neurons localized in the posterior hypothalamus (co-containing melanin-concentrating hormone), ventrolateral periaqueductal gray and the dorsal paragigantocellular reticular nucleus. In contrast, the exit from PS is induced by the inhibition of these neurons by a PS-gating system composed of GABAergic neurons localized in the ventrolateral periaqueductal gray and just ventral to it, and waking systems such as the pontine and medullary noradrenergic neurons and the hypothalamic hypocretin neurons. Finally, we review human neurological disorders of the network responsible for sleep and propose hypotheses on the mechanisms responsible for REM behavior disorder and narcolepsy.
Withania somnifera (ashwagandha) is a widely used herb in the Ayurvedic system of medicine. The objective of the present study was to elucidate the effect of W. somnifera root extract (Ws) alone or in combination with exogenous gamma-amino butyric acid (GABA), a GABA receptor agonist or with diazepam, a GABA receptor modulator against pentylenetetrazol (PTZ, iv) seizure threshold in mice. Minimal dose of PTZ (iv, mg/kg) needed to induce different phases (myoclonic jerks, generalized clonus and tonic extension) of convulsions were recorded as an index of seizure threshold. Ws (100 or 200 mg/kg, po) increased the PTZ seizure threshold for the onset of tonic extension phase whereas a lower dose (50 mg/kg, po) did not show any effect on the seizure threshold. Co-administration of a sub-effective dose of Ws (50 mg/kg, po) with a sub-protective dose of either GABA (25 mg/kg, ip) or diazepam (0.5 mg/kg, ip) increased the seizure threshold. The results suggested that the anticonvulsant effect of W. somnifera against PTZ seizure threshold paradigm involved the GABAAergic modulation.
In a recent survey, 106 local healers in Israel were interviewed concerning the use of Solanaceae as medicinal plants. The main findings reveal that: (a) only four species (Lycium europeaum, Solanum nigrum, Hyoscyamus aureus, Hyoscyamus albus) are extensively used today; (b) the use of some traditional plants has been almost abandoned (Datura spp., Mandragora autumnalis, Withania somnifera); (c) today all the plants are applied externally, they are rarely used as narcotics; (d) most use of these plants is local, only in a few cases is a uniform use found throughout the whole country, and in all ethnic groups; (e) the extensive distribution of modern, safe narcotics, sedatives and anaesthetics has reduced the use of the Solanaceae for these purposes.
The objective of this paper is to review the literature regarding Withania somnifera (ashwagandha, WS) a commonly used herb in Ayurvedic medicine. Specifically, the literature was reviewed for articles pertaining to chemical properties, therapeutic benefits, and toxicity.
This review is in a narrative format and consists of all publications relevant to ashwagandha that were identified by the authors through a systematic search of major computerized medical databases; no statistical pooling of results or evaluation of the quality of the studies was performed due to the widely different methods employed by each study.
Studies indicate ashwagandha possesses anti-inflammatory, antitumor, antistress, antioxidant, immunomodulatory, hemopoietic, and rejuvenating properties. It also appears to exert a positive influence on the endocrine, cardiopulmonary, and central nervous systems. The mechanisms of action for these properties are not fully understood. Toxicity studies reveal that ashwagandha appears to be a safe compound.
Preliminary studies have found various constituents of ashwagandha exhibit a variety of therapeutic effects with little or no associated toxicity. These results are very encouraging and indicate this herb should be studied more extensively to confirm these results and reveal other potential therapeutic effects. Clinical trials using ashwagandha for a variety of conditions should also be conducted.
This study was conducted to test the effectiveness of an abbreviated cognitive-behavioral insomnia therapy (ACBT) with primary
A single-blind, randomized group design was used in which study patients were randomized to either a brief, 2-session ACBT or a similarly brief intervention (SHC) that included only generic sleep hygiene recommendations.
A university-affiliated Department of Veterans Affairs medical center.
Twenty (2 women) veteran patients (M(age) = 51.0 yrs., SD = 13.7 years) who met criteria for chronic primary insomnia.
Participants completed sleep logs for 2 weeks and questionnaires to measures insomnia symptoms, sleep-related self-efficacy, and dysfunctional beliefs about sleep before treatment, during a 2-week posttreatment assessment, and again at a 3-month posttreatment follow-up. Statistical analyses showed that ACBT produced significantly larger improvements across a majority of outcome measures than did SHC. Case-by-case analyses showed that only the ACBT produced consistent positive effects across study patients, and a sizeable proportion of these patients receiving this treatment achieved clinically significant improvements by their study endpoints. Approximately 52% of those receiving the ACBT reported at least a 50% reduction in their wake time after sleep onset, and 55.6% of ACBT-treated patients who entered the study with pathologic scores on an Insomnia Symptom Questionnaire (ISQ), achieved normal ISQ scores by their final outcome assessment.
ACBT is effective for reducing subjective sleep disturbance and insomnia symptoms in primary care patients.
Ayurveda, the science of life, suggested that Aahar (diet), Nidra (sleep) and Brahmacharya (celibacy) plays an important role in maintaining healthy life. Nidranasha or Anidra (insomnia) is a common neurological disorder having difficulty in initiating or maintaining sound sleep. Conventional medical science frequently prescribes sedative and hypnotic like benzodiazepines drugs as a therapy of insomnia, which shows various side effects like tolerance and dependency. In traditional system several herbs are reported for treatment of insomnia. In this review, we have emphasises the role of Ashwagndha (Withania somnifera) towards the treatment of Insomnia.
Background
Patient online drug reviews are a resource for other patients seeking information about the practical benefits and drawbacks of drug therapies. Patient reviews may also serve as a source of postmarketing safety data that are more user-friendly than regulatory databases. However, the reliability of online reviews has been questioned, because they do not undergo professional review and lack means of verification.
Objective
We evaluated online reviews of hypnotic medications, because they are commonly used and their therapeutic efficacy is particularly amenable to patient self-evaluation. Our primary objective was to compare the types and frequencies of adverse events reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) with analogous information in patient reviews on the consumer health website Drugs.com. The secondary objectives were to describe patient reports of efficacy and adverse events and assess the influence of medication cost, effectiveness, and adverse events on user ratings of hypnotic medications.
Methods
Patient ratings and narratives were retrieved from 1407 reviews on Drugs.com between February 2007 and March 2018 for eszopiclone, ramelteon, suvorexant, zaleplon, and zolpidem. Reviews were coded to preferred terms in the Medical Dictionary for Regulatory Activities. These reviews were compared to 5916 cases in the FAERS database from January 2015 to September 2017.
Results
Similar adverse events were reported to both Drugs.com and FAERS. Both resources identified a lack of efficacy as a common complaint for all five drugs. Both resources revealed that amnesia commonly occurs with eszopiclone, zaleplon, and zolpidem, while nightmares commonly occur with suvorexant. Compared to FAERS, online reviews of zolpidem reported a much higher frequency of amnesia and partial sleep activities. User ratings were highest for zolpidem and lowest for suvorexant. Statistical analyses showed that patient ratings are influenced by considerations of efficacy and adverse events, while drug cost is unimportant.
Conclusions
For hypnotic medications, online patient reviews and FAERS emphasized similar adverse events. Online reviewers rated drugs based on perception of efficacy and adverse events. We conclude that online patient reviews of hypnotics are a valid source that can supplement traditional adverse event reporting systems.
This chapter presents hypotheses on the mechanisms responsible for the succession of the three vigilance states, namely waking, nonrapid eye movement (non-REM) (slow-wave sleep-SWS), and REM sleep (paradoxical sleep-PS). It can be proposed that waking is induced by the activity of multiple waking systems, including the serotonergic, noradrenergic, cholinergic, and hypocretin systems. At the onset of sleep, the SWS-active neurons are activated by the circadian clock localized in the suprachiasmatic nucleus and a hypnogenic factor, adenosine, which progressively accumulates in the brain during waking. A number of studies support the hypothesis that SWS results from the activation of GABAergic neurons localized in the ventrolateral preoptic nucleus. However, additional GABAergic systems have been described, localized in the parafacial, accumbens, and reticular thalamic nuclei, and these are also presented. In addition, the chapter discusses the fact that a large body of data strongly suggests that the switch from SWS to PS is due to the interaction of multiple populations of glutamatergic and GABAergic neurons localized in the posterior hypothalamus and the brainstem.
Background:
Insomnia is a prevalent sleep disorder that has not been well managed thus far. There are numerous medicaments for treatment of insomnia, but they have undesirable side effects that make herbal medicine a more viable option.
Objectives:
The effectiveness of a combination of Melissa officinalis L. (dry powder) and Nepeta menthoides Boiss. & Buhse (freeze-dried aqueous extract) on insomnia was evaluated.
Design and setting:
Insomniacs who met the entry criteria participated in a triple-blind randomized placebo-controlled clinical trial at the Persian Medicine (PM) clinic in Tehran.
Interventions:
The subjects received either 1000 mg of M. officinalis plus 400 mg N. menthoides or a placebo nightly for four weeks in accordance with prescriptions from the pharmaceutical manuscripts on PM and the results of previous studies.
Outcome measures:
The Pittsburgh Sleep Quality Index (PSQI), sleep diary, and Insomnia Severity Index (ISI) were used for assessment of insomnia.
Results:
Comparison of the treatment and placebo groups showed a significant decrease in the mean difference of ISI (4.97 ± 4.69 vs. 1.60 ± 3.70; p =; 0.002) and total PSQI (4.14 ± 3.69 vs. 1.42 ± 2.81; p = 0.001) scores in the treatment group. A significant increase was also observed in total sleep time of treatment group (p < 0.001) based on the sleep diary.
Conclusions:
A combination of M. officinalis and N. menthoides Boiss. & Buhse could be an alternative sleep improvement therapy.
Objectives:
Cognitive decline is often associated with the aging process. Ashwagandha (Withania somnifera (L.) Dunal) has long been used in the traditional Ayurvedic system of medicine to enhance memory and improve cognition.
Aim:
This pilot study was designed to evaluate the efficacy and safety of ashwagandha (Withania somnifera (L.) Dunal) in improving memory and cognitive functioning in adults with mild cognitive impairment (MCI).
Methods:
A prospective, randomized, double-blind, placebo-controlled study was conducted in 50 adults. Subjects were treated with either ashwagandha-root extract (300 mg twice daily) or placebo for eight weeks.
Results:
After eight weeks of study, the ashwagandha treatment group demonstrated significant improvements compared with the placebo group in both immediate and general memory, as evidenced by Wechsler Memory Scale III subtest scores for logical memory I (p = 0.007), verbal paired associates I (p = 0.042), faces I (p = 0.020), family pictures I (p = 0.006), logical memory II (p = 0.006), verbal paired associates II (p = 0.031), faces II (p = 0.014), and family pictures II (p = 0.006). The treatment group also demonstrated significantly greater improvement in executive function, sustained attention, and information-processing speed as indicated by scores on the Eriksen Flanker task (p = 0.002), Wisconsin Card Sort test (p = 0.014), Trail-Making test part A (p = 0.006), and the Mackworth Clock test (p = 0.009).
Conclusions:
Ashwagandha may be effective in enhancing both immediate and general memory in people with MCI as well as improving executive function, attention, and information processing speed.
Purpose:
Insomnia is problematic for older adults. After behavioral modifications fail to show adequate response, pharmacologic options are used. The pharmacokinetics of agents used to treat insomnia may be altered. This review focuses on the safety and efficacy of medications used to treat insomnia.
Methods:
A literature search of Medline, PubMed, and Embase was conducted (January 1966-June 2016). It included systematic reviews, randomized controlled trials, observational studies, and case series that had an emphasis on insomnia in an older population. Search terms included medications approved by the US Food and Drug Administration for insomnia: benzodiazepines (triazolam, estazolam, temazepam, flurazepam, and quazepam), nonbenzodiazepine receptor agonists (non-BzRAs; zaleplon, zolpidem, and eszopiclone), suvorexant, ramelteon, doxepin and trazodone. Off-label drugs such as other antidepressants, antihistamines, antipsychotics, gabapentin, pramipexole, tiagabine, valerian, and melatonin were also included.
Findings:
Cognitive behavioral therapy and sleep hygiene are considered initial therapy for insomnia. Benzodiazepines are discouraged in the geriatric population, especially for long-term use. Although non-BzRAs have improved safety profiles compared with benzodiazepines, their side effects include dementia, serious injury, and fractures, which should limit their use. Ramelteon has a minimal adverse effect profile and is effective for sleep-onset latency and increased total sleep time, making it a valuable first-line option. Although the data on suvorexant are limited, this drug improves sleep maintenance and has mild adverse effects, including somnolence; residual daytime sedation has been reported, however. Sedating low-dose antidepressants should only be used for insomnia when the patient has comorbid depression. Antipsychotic agents, pramipexole, and tiagabine have all been used for insomnia, but none has been extensively studied in an older population, and all have considerable adverse effects. Gabapentin may be useful in patients with restless leg syndrome or chronic neuropathic pain and insomnia. Diphenhydramine should be avoided in the elderly. Valerian and melatonin are unregulated products that have a small impact on sleep latency and can produce residual sedation.
Implications:
An ideal treatment for insomnia should help to improve sleep latency and sleep duration with limited awakenings and be without significant adverse effects such as daytime somnolence or decreased alertness. Cognitive behavioral therapy should always be first line treatment. Clinical inertia regarding previous prominent use of benzodiazepines and non-BzRAs will be a significant challenge for patients accustomed to their issuance. The future direction of insomnia treatment should have an emphasis on nonpharmacologic interventions, treating comorbid conditions, and focusing therapy on using benzodiazepines and non-BzRAs as last resorts.
In contrast to the association of insomnia with mental health, its association with physical health has remained largely unexplored until recently. Based on findings that insomnia with objective short sleep duration is associated with activation of both limbs of the stress system and other indices of physiological hyperarousal, which should adversely affect physical and mental health, we have recently demonstrated that this insomnia phenotype is associated with a significant risk of cardiometabolic and neurocognitive morbidity and mortality. In contrast, insomnia with normal sleep duration is associated with sleep misperception and cognitive-emotional arousal, but not with signs of physiological hyperarousal or cardiometabolic or neurocognitive morbidity. Interestingly, both insomnia phenotypes are associated with mental health, although most likely through different pathophysiological mechanisms. We propose that objective measures of sleep duration may become part of the routine evaluation and diagnosis of insomnia, and that these two insomnia phenotypes may respond differentially to biological versus psychological treatments.
Traditional Indian systems of medicine use roots of Withania somnifera (W. somnifera) for impotence, infertility treatment, stress, and the aging process. Although W. somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress, the molecular mechanism is not clear.
Our study uses high-resolution Nuclear Magnetic Resonance (NMR) spectroscopy to explore the scientific basis to reveal the pre- and post-treatment efficacy of W. somnifera on seminal plasma of infertile men-which remains unexplored to date.
A total of 180 infertile male patients were administered W. somnifera root powder at the rate of 5g/d for a three-month period. The study included age-matched, healthy men as a control (n=50) group. Proton NMR spectroscopy was used to measure lactate, alanine, glutamate, glutamine, citrate, lysine, choline, glycerophosphocholine (GPC), glycine, tyrosine, histidine, phenylalanine, and uridine in all seminal plasma samples. To appraise infertility levels, we also measured sperm concentration, motility, lipid peroxide, and hormonal perturbation.
W. somnifera therapy repairs the disturbed concentration of lactate, alanine, citrate, GPC, histidine, and phenylalanine in seminal plasma and recovers the quality of semen of post-treated compared to pre-treated infertile men. Serum biochemistry was also improved over post therapy in infertile men. Our findings reveal that W. somnifera not only reboots enzymatic activity of metabolic pathways and energy metabolism but also invigorates the harmonic balance of seminal plasma metabolites and reproductive hormones in infertile men.
The results suggest that W. somnifera may be used as an empirical therapy for clinical management and treatment of infertility.
Small molecules have been used since antiquity to regulate our sleep. Despite the explosion of diverse drugs to treat problems of too much or too little sleep, the detailed mechanisms of action and especially the neuronal targets by which these compounds alter human behavioural states are not well understood. Research efforts in model systems such as mouse, zebrafish and fruit fly are combining conditional genetics and optogenetics with pharmacology to map the effects of sleep-promoting drugs onto neural circuits. Recent studies raise the possibility that many small molecules alter sleep and wake via specific sets of critical neurons rather than through the global modulation of multiple brain targets. These findings also uncover novel brain areas as sleep/wake regulators and indicate that the development of circuit-selective drugs might alleviate sleep disorders with fewer side effects.
Insomnia is one of the most prevalent health concerns in the population and in clinical practice. Clinicians may be reluctant to address insomnia because of its many potential causes, unfamiliarity with behavioral treatments, and concerns about pharmacologic treatments.
To review the assessment, diagnosis, and treatment of insomnia in adults.
Systematic review to identify and summarize previously published quantitative reviews (meta-analyses) of behavioral and pharmacologic treatments for insomnia.
Insomnia is a common clinical condition characterized by difficulty initiating or maintaining sleep, accompanied by symptoms such as irritability or fatigue during wakefulness. The prevalence of insomnia disorder is approximately 10% to 20%, with approximately 50% having a chronic course. Insomnia is a risk factor for impaired function, development of other medical and mental disorders, and increased health care costs. The etiology and pathophysiology of insomnia involve genetic, environmental, behavioral, and physiological factors culminating in hyperarousal. The diagnosis of insomnia is established by a thorough history of sleep behaviors, medical and psychiatric problems, and medications, supplemented by a prospective record of sleep patterns (sleep diary). Quantitative literature reviews (meta-analyses) support the efficacy of behavioral, cognitive, and pharmacologic interventions for insomnia. Brief behavioral interventions and Internet-based cognitive-behavioral therapy both show promise for use in primary care settings. Among pharmacologic interventions, the most evidence exists for benzodiazepine receptor agonist drugs, although persistent concerns focus on their safety relative to modest efficacy. Behavioral treatments should be used whenever possible, and medications should be limited to the lowest necessary dose and shortest necessary duration.
Clinicians should recognize insomnia because of its effects on function and health. A thorough clinical history is often sufficient to identify factors that contribute to insomnia. Behavioral treatments should be used when possible. Hypnotic medications are also efficacious but must be carefully monitored for adverse effects.
Insomnia is a prevalent complaint in clinical practice that can present independently or comorbidly with another medical or psychiatric disorder. In either case, it might need treatment of its own. Of the different therapeutic options available, benzodiazepine-receptor agonists (BzRAs) and cognitive-behavioural therapy (CBT) are supported by the best empirical evidence. BzRAs are readily available and effective in the short-term management of insomnia, but evidence of long-term efficacy is scarce and most hypnotic drugs are associated with potential adverse effects. CBT is an effective alternative for chronic insomnia. Although more time consuming than drug management, CBT produces sleep improvements that are sustained over time, and this therapy is accepted by patients. Although CBT is not readily available in most clinical settings, access and delivery can be made easier through use of innovative methods such as telephone consultations, group therapy, and self-help approaches. Combined CBT and drug treatment can optimise outcomes, although evidence to guide clinical practice on the best way to integrate these approaches is scarce.
In many patients with depression, symptoms of insomnia herald the onset of the disorder and may persist into remission or recovery, even after adequate treatment. Several studies have raised the question whether insomniac symptoms may constitute an independent clinical predictor of depression. This meta-analysis is aimed at evaluating quantitatively if insomnia constitutes a predictor of depression.
PubMed, Medline, PsycInfo, and PsycArticles databases were searched from 1980 until 2010 to identify longitudinal epidemiological studies simultaneously investigating insomniac complaints and depressed psychopathology. Effects were summarized using the logarithms of the odds ratios for insomnia at baseline to predict depression at follow-up. Studies were pooled with both fixed- and random-effects meta-analytic models in order to evaluate the concordance. Heterogeneity test and sensitivity analysis were computed.
Twenty-one studies met inclusion criteria. Considering all studies together, heterogeneity was found. The random-effects model showed an overall odds ratio for insomnia to predict depression of 2.60 (confidence interval [CI]: 1.98-3.42). When the analysis was adjusted for outliers, the studies were not longer heterogeneous. The fixed-effects model showed an overall odds ratio of 2.10 (CI: 1.86-2.38).
The main limit is that included studies did not always consider the role of other intervening variables.
Non-depressed people with insomnia have a twofold risk to develop depression, compared to people with no sleep difficulties. Thus, early treatment programs for insomnia might reduce the risk for developing depression in the general population and be considered a helpful general preventive strategy in the area of mental health care.
Insomnia is the most common sleeping disorder and has been recognized as a major public health issue, associated with a high societal cost. The aim of this review is firstly to understand how the socio-demographic and career characteristics of insomniacs may influence the economical consequences of this disease. Secondly, it also tries to explain how patients seek help to cope with their insomnia. The review aims to carefully describe the possible links between insomnia and public health concerns as to point out what are the certitudes and the missing data on the consequences of insomnia on work, economics, accidents, costs and health related quality of life (HrQol).
The effect of the methanol extract of Withania somnifera (mWS) on the gonadotropin releasing hormone (GnRH) neuron was examined in juvenile mice using the whole cell patch clamp technique. GnRH neurons are the fundamental regulators of the pulsatile release of GnRH needed for puberty and fertility. GnRH neurons were depolarized by bath application of the mWS (400 ng/microl) under the condition of a high Cl(-) pipette solution in current clamp mode. In voltage clamp mode, mWS induced reproducible inward currents (31.7 +/- 5.51 pA, n = 14). The mWS-induced inward currents persisted in the presence of tetrodotoxin (TTX, 0.5 microM), but were suppressed by bicuculline methiodide (BMI, 20 microM), a GABA(A) receptor antagonist. These results show that mWS affects the neuronal activities by mediating the GABA(A) receptor, which suggests that WS contains an ingredient with possible GABAmimetic activity.
Most sedative-hypnotics used in insomnia treatment target the gamma-aminobutyric acid (GABA)(A) receptors. A vast repertoire of GABA(A) receptor subtypes has been identified and displays specific electrophysiological and functional properties. GABA(A)-mediated inhibition traditionally refers to 'phasic' inhibition, arising from synaptic GABA(A) receptors which transiently inhibit neurons. However, there is growing evidence that peri- or extra-synaptic GABA(A) receptors are continuously activated by low GABA concentrations and mediate a 'tonic' conductance. This slower type of signaling appears to play a key role in controlling cell excitability. This review aims at summarizing recent knowledge on GABA transmission, including the emergence of tonic conductance, and highlighting the importance of GABA(A) receptor heterogeneity. The mechanism of action of sedative-hypnotic drugs and their effects on sleep and the electroencephalogram will be reported. Furthermore, studies using genetically engineered mice will be emphasized, providing insights into the role of GABA(A) receptors in mechanisms underlying physiological and pharmacological sleep. Finally, we will address the potential of GABA(A) receptor pharmacology for the treatment of insomnia.
A methanolic extract of W. somnifera root inhibited the specific binding of [3H]GABA and [35S]TBPS, and enhanced the binding of [3H]flunitrazepam to their putative receptor sites. The extract (5 micrograms) inhibited [3H]GABA binding by 20 +/- 6 per cent whereas a concentration of 1 mg of the extract produced 100 per cent inhibition. The extract (5-100 micrograms) produced 20 +/- 4 to 91 +/- 16 per cent enhancement of [3H]flunitrazepam binding. In functional studies using 36Cl-influx assay in mammalian spinal cord neurons, W. somnifera root extract increased 36Cl-influx in the absence of GABA. This effect on 36Cl-influx was blocked by bicuculline and picrotoxin; and enhanced by diazepam. These results suggest that the W. somnifera extract contains an ingredient which has a GABA-mimetic activity.
Highlights aspects of insomnia (INS), which may occur in transient and short-term or chronic forms. Transient INS generally occurs in people who usually have normal sleep and are experiencing acute stress and environmental disturbances. Chronic INS usually results from underlying medical or psychiatric disorders. Between one-third and two-thirds of patients with chronic INS have a recognizable psychiatric illness. Conditioned anxiety about falling asleep or the consequences of sleep loss may perpetuate INS to varying degrees in all chronic INS patients. Management of INS may include counseling and psychotherapy, behavioral and biofeedback techniques, and pharmacotherapy. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Despite the prevalence of sleep complaints among psychiatric patients, few questionnaires have been specifically designed to measure sleep quality in clinical populations. The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score. Clinical and clinimetric properties of the PSQI were assessed over an 18-month period with "good" sleepers (healthy subjects, n = 52) and "poor" sleepers (depressed patients, n = 54; sleep-disorder patients, n = 62). Acceptable measures of internal homogeneity, consistency (test-retest reliability), and validity were obtained. A global PSQI score greater than 5 yielded a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p less than 0.001) in distinguishing good and poor sleepers. The clinimetric and clinical properties of the PSQI suggest its utility both in psychiatric clinical practice and research activities.
The aim of this study was to assess whether there is an association between chronic insomnia and the activity of the stress system. Fifteen young adult insomniacs (<40 years) were studied. After an adaptation night, each subject was recorded in the sleep laboratory for three consecutive nights. During this period, 24-hour urine specimens were collected for measurements of urinary free cortisol (UFC), catecholamines, and growth hormone (GH). The 24-hour UFC levels were positively correlated with total wake time (p=0.05). In addition, 24-hour urinary levels of catecholamine metabolites, DHPG, and DOPAC were positively correlated with percent stage 1 sleep (p<0.05) and wake time after sleep onset (WTASO) (p<0.05). Norepinephrine tended to correlate positively with percent stage 1 sleep (p=0.063) and WTASO (p=0.074), and negatively with percent slow-wave sleep (p=0.059). Twenty-four-hour urinary GH excretion was detectable in only three insomniacs, two of whom had low indices of sleep disturbance. We conclude that, in chronic insomnia, the activity of both limbs of the stress system (i.e., the HPA axis and the sympathetic system) relates positively to the degree of objective sleep disturbance.
Hypoglycemic, diuretic and hypocholesterolemic effects of roots of W. somnifera (ashvagandha) were assessed on human subjects. Six mild NIDDM subjects and six mild hypercholesterolemic subjects were treated with the powder of roots of W. somnifera for 30 days. Suitable parameters were studied in the blood and urine samples of the subjects along with dietary pattern before and at the end of treatment period. Decrease in blood glucose was comparable to that of an oral hypoglycemic drug. Significant increase in urine sodium, urine volume, significant decrease in serum cholesterol, triglycerides, LDL (low density lipoproteins) and VLDL (very low density lipoproteins) cholesterol were observed indicating that root of W. somnifera is a potential source of hypoglycemic, diuretic and hypocholesterolemic agents. Clinical observations revealed no adverse effects.
World-wide use of herbal medicines is increasing, following regulatory and manufacturing developments. Herbs are attractive alternative medications to many patients with sleep disorders, who may be averse to using conventional drugs. We review here the most common herbal stimulants and sedatives. Caffeine, in herbal teas, black tea, coffee, soft drinks and pharmaceuticals, is used widely to control sleepiness, but more research is needed on its use in sleep disorders. Ephedra, and its constituent ephedrine, are used in both stimulant and weight loss preparations, sometimes with caffeine; safety concerns have arisen with this practice. Yohimbe is another herb used in stimulant and body-building preparations which has safety concerns. Asian and Siberian ginseng have been traditionally used for fatigue, and have some supportive experimental evidence for this use. Herbal sedatives also have some evidence for efficacy; the observations that certain plant flavonoid compounds bind to benzodiazepine receptors adds interest to their use. Valerian and kava have received the most research attention; both have decreased sleep onset time and promoted deeper sleep in small studies, and kava also shows anxiolytic effects. German chamomile, lavender, hops, lemon balm and passionflower are reputed to be mild sedatives but need much more experimental examination.