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Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: An experimental study

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Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: An experimental study

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Abstract

The roots of Withania somnifera (WS) are used extensively in Ayurveda, the classical Indian system of medicine, and WS is categorized as a rasayana, which are used to promote physical and mental health, to provide defence against disease and adverse environmental factors and to arrest the aging process. WS has been used to stabilize mood in patients with behavioural disturbances. The present study investigated the anxiolytic and antidepressant actions of the bioactive glycowithanolides (WSG), isolated from WS roots, in rats. WSG (20 and 50 mg/kg) was administered orally once daily for 5 days and the results were compared by those elicited by the benzodiazepine lorazepam (0.5 mg/kg, i.p.) for anxiolytic studies, and by the tricyclic anti-depressant, imipramine (10 mg/kg, i.p.), for the antidepressant investigations. Both these standard drugs were administered once, 30 min prior to the tests. WSG induced an anxiolytic effect, comparable to that produced by lorazepam, in the elevated plus-maze, social interaction and feeding latency in an unfamiliar environment, tests. Further, both WSG and lorazepam, reduced rat brain levels of tribulin, an endocoid marker of clinical anxiety, when the levels were increased following administration of the anxiogenic agent, pentylenetetrazole. WSG also exhibited an antidepressant effect, comparable with that induced by imipramine, in the forced swim-induced 'behavioural despair' and 'learned helplessness' tests. The investigations support the use of WS as a mood stabilizer in clinical conditions of anxiety and depression in Ayurveda.

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... To date, animal studies have demonstrated the ability of WS to decrease anxiety-like behavior in several animal models of disease, including stress [17,54,[73][74][75], sleep deprivation [45,76,77], social isolation [78], and neuroinflammation [79] (Table 3). Anxiety-like behavior was most commonly evaluated using the elevated plus maze [74,75,77,80,81]: a test in which rodents are placed in an elevated plus-shaped maze with open and closed arms, where increased entries and/or time spent in the open arms reflect anti-anxiety behavior [82]. The elevated plus maze test has been validated to assess pharmaceutical agents for antianxiety activity in rodents [82]. ...
... However, the validity of this test as a measure of anxiety is questionable [84,85]. Other measures used to evaluate anxiety-like behavior in rodent studies included the open field test [75], social interaction test [81], novelty-suppressed feeding latency test [81], and pentylenetetrazol-induced defecation and urination [17]. A zebrafish model of benzo[a]pyrene-induced neurotoxicity used the light/dark preference test and the novel tank diving test to assess anxietylike behavior [86]. ...
... However, the validity of this test as a measure of anxiety is questionable [84,85]. Other measures used to evaluate anxiety-like behavior in rodent studies included the open field test [75], social interaction test [81], novelty-suppressed feeding latency test [81], and pentylenetetrazol-induced defecation and urination [17]. A zebrafish model of benzo[a]pyrene-induced neurotoxicity used the light/dark preference test and the novel tank diving test to assess anxietylike behavior [86]. ...
Article
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.
... Anti-anxiety (reduced tribulin levels in rat brain) and Antidepressant effect Bhattacharya et al. (2000) Withanolide B ...
... In 2000, Bhattacharya et al., isolated the bioactive compound glycowithanolides from Ashwagandha roots and investigated its potential as antidepressant at the dose of 20 and 50 mg/kg. Glycowithanolides were found to exhibit comparable antidepressant effect to imipramine in behavioural despair and learned helplessness induced by forced swim tests Thereby, supporting the use of Ashwagandha as mood stabilizer (Bhattacharya et al., 2000). ...
... Nootropic effects of various herbs including Ashwagandha plays an important role in treating and preventing ADHD. Multiple clinical trials and animal studies have reported its use in anxiety, cognitive and neurological disorders (Bhattacharya et al., 2000). Kanyaiyaa and colleagues, reported immunomodulatory and CNS effects of new glycowithanolides mainly sitoindoside IX and sitoindoside X, at dose of 50-200 mg/kg (Kanyaiyaa et al., 2014). ...
Article
Ethnopharmacological relevance: Withania somnifera (Family: Solanaceae), commonly known as Ashwagandha or Indian ginseng is distributed widely in India, Nepal, China and Yemen. The roots of plant consist of active phytoconstituents mainly withanolides, alkaloids and sitoindosides and are conventionally used for the treatment of multiple brain disorders. Aim of the review: This review aims to critically assess and summarize the current state and implication of Ashwagandha in brain disorders. We have mainly focussed on the reported neuroactive phytoconstituents, available marketed products, pharmacological studies, mechanism of action and recent patents published related to neuroprotective effects of Ashwagandha in brain disorders. Materials and methods: All the information and data was collected on Ashwagandha using keywords “Ashwagandha” along with “Phytoconstituents”, “Ayurvedic, Unani and Homeopathy marketed formulation”, “Brain disorders”, “Mechanism” and “Patents”. Following sources were searched for data collection: electronic scientific databases such as Science Direct, Google Scholar, Elsevier, PubMed, Wiley On-line Library, Taylor and Francis, Springer; books such as AYUSH Pharmacopoeia; authentic textbooks and formularies. Results: Identified neuroprotective phytoconstituents of Ashwagandha are sitoindosides VII–X, withaferin A, withanosides IV, withanols, withanolide A, withanolide B, anaferine, beta-sitosterol, withanolide D with key pharmacological effects in brain disorders mainly anxiety, Alzheimer's, Parkinson's, Schizophrenia, Huntington's disease, dyslexia, depression, autism, addiction, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder and bipolar disorders. The literature survey does not highlight any toxic effects of Ashwagandha. Further, multiple available marketed products and patents recognized its beneficial role in various brain disorders; however, very few data is available on mechanistic pathway and clinical studies of Ashwagandha for various brain disorders is scarce and not promising. Conclusion: The review concludes the results of recent studies on Ashwagandha suggesting its extensive potential as neuroprotective in various brain disorders as supported by preclinical studies, clinical trials and published patents. However vague understanding of the mechanistic pathways involved in imparting the neuroprotective effect of Ashwagandha warrants further study to promote it as a promising drug candidate.
... These observations imply that there might be a correlation between decreased serotonergic activity and ethanol withdrawal. In earlier studies Bhattacharya et al [29] found that ASW exhibited an antidepressant effect, comparable with that induced by imipramine, in the forced swiminduced 'behavioural despair' and 'learned helplessness'. Tripathi et al [30] demonstrated that chronic dosing with ASW downregulated 5-HT1 and upregulates 5-HT2 receptors in the rat brain; these changes were accompanied by a decrease in behavioral indices of anxiety and depression. ...
... This test has further witnessed the increase in number of line crossing activity by mice which may be the consequence of anxiolytic activity of ASW at higher dose (500 mg/kg) similar to that of diazepam. In the earlier studies Bhattacharya et al [29] showed that, in rats, ASW glycowithanolides had an anxiolytic effect comparable to that of lorazepam. This finding was obtained in the elevated plus-maze as well as in the test of social interaction and feeding latency in an unfamiliar environment. ...
Article
Objective: To evaluate the effect of Ashwagandha (ASW) in attenuation of alcohol withdrawal in ethanol withdrawal mice model. Methods: Alcohol dependence was induced in mice by the oral, once-daily administration of 10% v/v ethanol (2 g/kg) for one week. Once the animals were withdrawn from alcohol, the efficacy of ASW (200mg/kg and 500mg/kg) in comparison with diazepam (1 mg/kg) in the attenuation of withdrawal was studied using, pentylenetetrazole (PTZ) kindling test for seizure threshold, forced swim test (FST) for depression and locomotor activity (LCA) in open field test (OFT). 6 hours after the last ethanol administration, seizure threshold was measured in all the groups by administering the convulsant drug, PTZ with a subconvulsive dose of 30 mg/kg i.p). In FST, mice were forced to swim and the total duration of immobility (seconds) was measured during the last 4 min of a single 6-min test session. In OFT, number of crossings of the lines marked on the floor was recorded for a period of 5 min. Results: Compared to ethanol group, ASW (500 mg/Kg) has suppressed the PTZ kindling seizures in ethanol withdrawal animals [0% convulsion], FST has shown decreased immobility time and OFT has exhibited increase in the number of line crossing activity by mice which may be the consequence of anxiolytic activity of ASW similar to that of diazepam. Conclusions: The present study provides satisfactory evidence to use ASW as a safe and reliable alternative to diazepam in alcohol withdrawal conditions. Contents lists available at ScienceDirect
... The biological activities of W. somnifera are anxiolytic, antidepressant, antifungal (Bhattacharya et al., 2000b), antimicrobial (Girish et al., 2006), antimalarial (Dikasso et al., 2006), apoptotic (Senthil et al., 2007), chondroprotective (Sumantran et al., 2007), cardioprotective (Hamza et al., 2008), immunomodulator (Davis and Kuttan, 2000), and neuroprotective (Sankar et al., 2007), promote inhibition of COX-2 enzyme (Jayaprakasam et al., 2003), and promote learning and memory in Alzheimer's disease (AD) (Bhattacharya et al., 1995). Numerous studies indicated that Ashwagandha possesses antioxidant, antitumor, antistress, anti-inflammatory, immunomodulatory, hematopoietic, antiaging, anxiolytic, antidepressive, and rejuvenating properties, and that it also influences various neurotransmitter receptors in the central nervous system (CNS) (Pattipati et al., 2003). ...
... Thus, they concluded that WSG tended to normalize the augmented SOD and LPO activities and enhance the activities of CAT and GPx. Their results indicate that at least part of the chronic stress-induced pathology may be due to oxidative stress, which is mitigated by WSG, lending support to the clinical use of the plant as an antistress adaptogen (Bhattacharya et al., 2000b). The brain is relatively more susceptible to free radical damage than other tissues because it is rich in lipids and iron, both of which are known to be important in Bhattacharya et al. (1997a,b) 2. ...
Chapter
Withania somnifera, commonly known as Ashwagandha (winter cherry), is an important medicinal plant that has been used in Ayurvedic and indigenous medicine for more than 3000 years. Some herbalists refer to Ashwagandha as Indian ginseng. The plant extract has many bioactive compounds that exert antioxidant, antiinflammatory, and immunomodulatory activities. The plant extract and its bioactive compounds are used in the prevention and treatment of many diseases, such as arthritis, impotence, amnesia, anxiety, cancer, neurodegenerative and cardiovascular diseases, and others. This chapter describes multiple health benefits of Ashwagandha in humans and animals.
... In the Ayurvedic system of medicines, roots and leaves of the plant were considered phytotherapeutic agents to cure various ailments. Various clinical and preclinical trials exhibited the plant's potential in curing hepatotoxicity (10), neurological disorders (11), anxiety (12), Parkinson's disease (13), and hyperlipidemia (4,14). The fruits contained considerable amounts of saponins and leaves possessed insect repellent properties (15). ...
Article
Full-text available
Withania somnifera L. is a multipurpose medicinal plant of family Solanaceae occurring abundantly in sub-tropical regions of the world. The folk healers used the plant to treat several diseases such as fever, cancer, asthma, diabetes, ulcer, hepatitis, eyesores, arthritis, heart problems, and hemorrhoids. The plant is famous for the anti-cancerous activity, low back pain treatment, and muscle strengthening, which may be attributed to the withanolide alkaloids. W. somnifera is also rich in numerous valued secondary metabolites such as steroids, alkaloids, flavonoids, phenolics, saponins, and glycosides. A wide range of preclinical trials such as cardioprotective, anticancer, antioxidant, antibacterial, antifungal, anti-inflammatory, hepatoprotective, anti-depressant, and hypoglycemic have been attributed to various parts of the plant. Different parts of the plant have also been evaluated for the clinical trials such as male infertility, obsessive-compulsive disorder, antianxiety, bone and muscle strengthening potential, hypolipidemic, and antidiabetic. This review focuses on folk medicinal uses, phytochemistry, pharmacological, and nutrapharmaceutical potential of the versatile plant.
... WS root extract (500 mg/kg BW for 6 days for 6 weeks; Wistar rats) prevented memory impairment and other behavioral deficits in animal model of post-traumatic stress disorders by preserving antioxidant signaling pathways and increasing BDNF levels (Alzoubi et al., 2019). WS root extract as well as bioactive glycowithanolides (20 and 50 mg/kg BW for 5 days) showed antidepressant and anxiolytic action in Charles Foster rat model and effect was comparable with pharmacological drugs lorazepam and imipramine (Bhattacharya et al., 2000). WS also alleviated depressive and anxiety symptoms and improved cognitive performance in patients with bipolar disorder (500 mg/day for 8 weeks) and schizophrenia (1000 mg/day for 12 weeks) (Chengappa et al., 2013(Chengappa et al., , 2018Gannon et al., 2019). ...
Article
Brain and neuronal circuits constitute the most complex organ networks in human body. They not only control and coordinate functions of all other organs, but also represent one of the most-affected systems with stress, lifestyle and age. With global increase in aging populations, these neuropathologies have emerged as major concern for maintaining quality of life. Recent era has witnessed a surge in nutritional remediation of brain dysfunctions primarily by “nutraceuticals” that refer to functional foods and supplements with pharmacological potential. Specific dietary patterns with a balanced intake of carbohydrates, fatty acids, vitamins and micronutrients have also been ascertained to promote brain health. Dietary herbs and their phytochemicals with wide range of biological and pharmacological activities and minimal adverse effects have gained remarkable attention as neuro-nutraceuticals. Neuro-nutraceutical potentials of herbs are often expressed as effects on cognitive response, circadian rhythm, neuromodulatory, antioxidant and anti-inflammatory activities that are mediated by effects on gene expression, epigenetics, protein synthesis along with their turnover and metabolic pathways. Epidemiological and experimental evidence have implicated enormous applications of herbal supplementation in neurodegenerative and psychiatric disorders. The present review highlights the identification, experimental evidence and applications of some herbs including Bacopa monniera, Withania somnifera, Curcuma longa, Helicteres angustifolia, Undaria pinnatifida, Haematococcus pluvialis, and Vitis vinifera, as neuro-nutraceuticals.
... The isolation of ashwagandha, a bioactive glycowithanolides from roots of the plant in rats elicited pharmacological actions those like benzodiazepine, lorazepam for anxiety and imipramine for depression. 26 In a clinical study involving 30 subjects Withania somnifera enhanced sensorimotor function, auditory and mental ability, this study strengthens the role of ashwagandha in memory and concentration. 27 During the course of intensive learning, an increase in SWA observed in EEG power between 0.5 and 4 Hz during NREM sleep stage. ...
Article
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Background: Ashwagandha (Withania somnifera), a known traditional medicine used in Ayurveda system of medicine, native to the India. Poor quality sleep always looked as serious complaint as it disrupts sleep. The natural phytoconstituents present in the ashwagandha believed to be adaptogen that helps the body to adapt stress by normalizing or correcting through balancing immune and neuroendocrine system. The mechanism that enhances sleep quality in the presence of ashwagandha is still unknown. Based on all available studies we investigated the effects of hydroalcoholic extract of ashwagandha effects on various bands of the electroencephalogram (EEG) to ascertain its role in behavior and sleep in rats. Material and methods: The present study explored in Wistar rats of either sex (n=12) used to record EEG in the presence of ashwagandha extracts (25mg/kg body weight). The previous studies revealed sleep promoting character of GABA very well documented in governing sleep and Withania somnifera known to posses mild to moderate hypnotic activity. We used conventional model for quantifying EEG in presence of ashwagandha extract and investigated its possible role in memory, behavior and sleep. Withania somnifera extract administered orally (25mg/kg) for electrophysiological recordings. Comparison made between post administration of extract with baseline recording employing vehicle and is considered as control. The changes in various bands of EEG noticed following administration of ashwagandha extract. Results: The Withania somnifera extract increased electrophysiological properties in delta (p<0.001) and gamma (p<0.003) bands and was found to be statistically significant. Statistically significant changes not observed in theta and alpha band power but beta band power was reduced in its influence (p<0.013). Conclusion: The present study revealed enhanced activity of the slow wave in presence of ashwagandha extract and divulged the details of its role in sleep and memory
... Even though findings from these two studies were generally positive, further research on clinical populations is required. In several animal trials, the anxiolytic effects of ashwagandha have been confirmed (Alzoubi et al., 2019;Bhattacharya et al., 2000;Candelario et al., 2015;Gupta and Kaur, 2018;Kaur et al., 2017) and may be derived from its influence on the hypothalamic-pituitary-adrenal axis, γ-aminobutyric acid, inflammation, and intestinal microbiota (Candelario et al., 2015;Dey et al., 2018;Gupta and Kaur, 2018;Kaur et al., 2017). As an intervention to enhance sexual function and fertility, research is promising, particularly as a natural treatment for male infertility. ...
Article
Ashwagandha is a medicinal plant that has been used in Ayurvedic and indigenous medicine for over 3,000 years. Because interest and the popularity of ashwagandha has increased in several Western countries, there are an increasing number of human trials evaluating its efficacy across a range of conditions. Based on the PRISMA guidelines, human trials assessing the effects of ashwagandha on mental and/or physical conditions, and/or human performance, used as a stand-alone or adjunct intervention, and delivered as a single ingredient, were eligible for inclusion in this systematic review. Forty-one studies were identified examining the effects of ashwagandha on stress and anxiety, sexual function and fertility, athletic performance, cognitive performance, pain, fatigue, thyroid function, schizophrenia, diabetes, obsessive-compulsive disorder, insomnia, hypercholesterolemia, and tuberculosis. Results from most of these studies indicated positive effects from ashwagandha intake, although treatment dose, duration, and extract types varied significantly. Moreover, trials often comprised of small sample sizes and were primarily conducted in India (32 studies). Overall, the strongest evidence for therapeutic efficacy of ashwagandha is the alleviation of stress and anxiety symptoms. The results from this systematic review suggest ashwagandha has a potentially large array of therapeutic applications. However, while promising, the significant heterogeneity across studies and the limited number of investigations means further research utilising robust and adequately-powered study designs are required.
... Some of the plant drugs investigated in recent years for antidepressant activity have demonstrated promising results. For example St. John's Wort (Hypericum perforatum) (Butterweek, et al., 1997), Hypericum reflexum L (Sánchez-Mateo et al., 2007), Glycyrrhiza glabra L (Dinesh and Amandeep, 2006), Kielmeyera cariacea (Martins, et al., 2006), Withania somnifera (Bhattacharya et al., 2000), etc have been reported to produce significant antidepressant effect. Similarly, a compound formulation having Valeriana velchii, Convolvulus microphylus, Plumbago zeylanica, Boswellia serrata, Acorus calamus as its ingredients, has been reported to possess antidepressant activity (Shalam, 2007). ...
Research
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Depression, Malikholiya, Unani Medicine, Majoon Najah
... In the same study, it was also observed that anxiety levels reduced by 41% in participants taking ashwagandha, which compared favorably to the 24% reduction experienced in participants taking a placebo. Further confirmation of the mood-enhancing effects of ashwagandha was provided by positive overall improvements in the DASS-21, a measure of depressive, anxiety, and stress symptoms 12 . ...
Article
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Background: This study provides a path for many studies that may have been forgotten in the past to the use of modern-day knowledge supporting the use of traditional treatments, specifically Withania somnifera (ashwagandha). Primary study objective: The primary objective of this study was to bring back traditional therapy that could prove to be economically beneficial and possibly helpful to many clients with depression with few or no associated adverse events. Intervention: The key components of ashwagandha include 12 alkaloids and 35 withanolides, which have been proven in various studies to be beneficial in the treatment of anxiety and stress. While research supports that withanolides and alkaloides work as antidepressants and are the main reason ashwagandha is beneficial for depression, the mechanism of action in unknown. Studies also show that withanolides may bolster the immune system, increase stamina, fight inflammation and infection, combat tumors, reduce stress, revive the libido, protect the liver and soothe jangled nerves. Both of these molecules are steroidal and are similar in action and appearance. Ashwagandha stimulates the activation of immune system cells such as lymphocytes and has also been shown to inhibit inflammation and improve memory in animal experiments.
... In addition, 20 and 50 mg/kg of aqueous concentrate of WS roots in inbred Charles Foster strain male rats could show its GABA-mimetic effect hence can act as a potential antidepressant [52]. WS has a remarkable quality to reduce the corticosterone levels in treated mice compared to vehicle-treated ones which were subjected to restraint stress for 30 days straight [47]. ...
Article
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Withania somnifera (L.) Dunal (Solanaceae) has been used as a traditional Rasayana herb for a long time. Traditional uses of this plant indicate its ameliorative properties against a plethora of human medical conditions, viz. hypertension, stress, diabetes, asthma, cancer etc. This review presents a comprehensive summary of the geographical distribution, traditional use, phytochemistry, and pharmacological activities of W. somnifera and its active constituents. In addition, it presents a detailed account of its presence as an active constituent in many commercial preparations with curative properties and health benefits. Clinical studies and toxicological considerations of its extracts and constituents are also elucidated. Comparative analysis of relevant in-vitro, in-vivo, and clinical investigations indicated potent bioactivity of W. somnifera extracts and phytochemicals as anti-cancer, anti-inflammatory, apoptotic, immunomodulatory, antimicrobial, anti-diabetic, hepatoprotective, hypoglycaemic, hypolipidemic, cardio-protective and spermatogenic agents. W. somnifera was found to be especially active against many neurological and psychological conditions like Parkinson's disease, Alzheimer's disease, Huntington's disease, ischemic stroke, sleep deprivation, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder, bipolar disorder, anxiety, depression, schizophrenia and obsessive-compulsive disorder. The probable mechanism of action that imparts the pharmacological potential has also been explored. However, in-depth studies are needed on the clinical use of W. somnifera against human diseases. Besides, detailed toxicological analysis is also to be performed for its safe and efficacious use in preclinical and clinical studies and as a health-promoting herb.
... A glycowithanolide-enriched fraction from Withania somnifera exhibited antidepressant effects in the FST in rats [377]. Shah et al. [378] tested an extract of ashwagandha alone as well as in combination with standard drugs; in both cases, imipramine and fluoxetine produced a significant decrease in the mean immobility time in the FST, an effect that seems to be mediated partly through the α-adrenoceptor and alterations in the levels of central biogenic amines [378]. ...
Article
Medicinal plants and their extracts are natural remedies with enormous potential for treating various diseases, including depression and anxiety. In the case of depression, hundreds of plants have traditionally been used in folk medicine for generations. Different plant extracts and natural products have been analyzed as potential antidepressant agents with validated models to test for antidepressant-like effects in animals, although other complementary studies have also been employed. Most of these studies focus on the possible mediators implicated in these potential effects, with dopamine, serotonin, and noradrenaline being the principal neurotransmitters implicated, both through interference with receptors and with their metabolism by monoamino oxidases, as well as through neuro-endocrine and neuroprotective effects. There are approximately 650 reports of antidepressant-like medicinal plants in PubMed; 155 of them have been compiled in this review, with a relevant group yielding positive results. Saffron and turmeric are the most relevant species studied in both preclinical and clinical studies; St. Johnʼs wort or kava have also been tested extensively. To the best of our knowledge, no review to date has provided a comprehensive understanding of the biomolecular mechanisms of action of these herbs or of whether their potential effects could have real benefits. The purpose of this narrative review is to provide an update regarding medicinal plants from the year 2000 to the present to examine the therapeutic potential of these antidepressant-like plants in order to contribute to the development of new therapeutic methods to alleviate the tremendous burden that depression causes worldwide.
... Obecne w ashwagandzie glikowitanolidy podawane szczurom, u których wywołano lęk pentetrazolem, zmniejszyły również poziom tribuliny (markera lęku klinicznego) w mózgu zwierząt. Ponadto, wykazywały działanie przeciwlękowe, porównywalnie do działania leków przeciwdepresyjnych [23]. W innym badaniu klinicznym, podczas którego testowano bezpieczeństwo oraz skuteczność działania ekstraktu bogatego w związki korzenia witanii ospałej u ludzi, poziom kortyzolu w surowicy spadał, nie powodując przy tym żadnych skutków ubocznych. ...
Article
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Farmacja Polska, ISSN 0014-8261 (print); ISSN 2544-8552 (on-line) Ashwagandha (Withania somnifera L.)-the plant with proven health-promoting properties Ashwagandha (Withania somnifera (L.) Dunal) belongs to the Solanacae family and is also known as gooseberry, Indian ginseng and winter cherry. It is a plant that has played a significant role in Ayurvedic medicine for thousands of years. Its natural habitat is southeast Asia. It has the form of a small or medium sized semi-shrub covered with characteristic very short hairs of silver-grey color. The chemical composition of the plant is very rich, but its main active ingredients are vitanolids, which are naturally occurring steroid lactones and alkaloids. It is an important ingredient in many Ayurvedic formulations, which are currently commercialized in India and other countries of the world. Ayurvedic formulations containing W. somnifera are prescribed as analgesic for a variety of musculoskeletal disorders, hypertension, in gynecological practice for vaginitis, for stimulating sexual impulses and during pregnancy for breast development. The plant is also applied as dietary supplement and in the form of decoction that is used as nutrient and health restorative to pregnant and old people. In Ayurvedic systems of medicine, the leaves, flowers, fruits, seeds and roots of W. somnifera are used for a therapeutic purposes. Moreover, W. somnifera is also known as a powerful adaptogen that enhances the body's resilience to stress, function of the brain and nervous system. Futhermore, Ashwagandha improves memory and function of the reproductive system promotes a healthy sexual and reproductive balance, amends the cell-mediated immunity and increases the body's defense against disease and possess anti-inflammatory, anticancer and anti-arthritic activities. W. somnifera has also other multipurpose medicinal uses which are supported by different clinical and preclinical trials including immunomodulatory, antidiabetic, neurological inflammatory disorders, hemopoietic and Parkinson's disease. Additionally it is also useful as antibiotic, antioxidant, deobstruent, aphrodisiac, abortifacient, diuretic and sedative agent. Moreover, this plant is also useful to treat bronchitis, asthma, ulcer, cancer, emaciation, insomnia, and senile dementia. However, the best known and most frequently used action is its toning effect on the nervous system. Contemporary research confirms that it is a strong adaptogen, i.e. it can effectively support increasing resistance to stress. Many of Ashwagandha's therapeutic actions still need to be studied. Moreover, this study will allow to discover new potential applications of this plant. To jest artykuł o otwartym dostępie, na licencji CC BY NC https://creativecommons.org/licenses/ by-nc/4.0/
... Furthermore, high predicted BBB permeability in our study enabled withametelin to reach the target site in brain. Previous studies affirm curative potential of glycowithanolides in chronic stress-induced depression in in-vivo models (Bhattacharya et al., 2000, Ghosal et al., 1989. However, in-depth studies are required to justify these proposed mechanisms of depression. ...
Article
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Withanolides are natural medicinal agents whose safety and therapeutic profiles make them valuable to mankind. Among multiple withanolides, withametelin is underexplored. The present study was aimed to create a general biological profile of isolated withametelin from Datura innoxia Mill. targeting different biological models. In-silico studies include drug-likeliness, pharmacokinetics, toxicity, molecular targets and cytotoxicity to cancer cell lines predictions. In silico directed preliminary in-vitro evaluation comprised of cancer/normal cell cytotoxicity, DPPH and protein kinase inhibition assays while in-vivo bioac-tivities include antiinflammatory, analgesic, antidepressant and anticoagulant assays. Pharmacological findings were strengthened by molecular docking studies to check interactions with various proteins and to propose the future path of studies. Results indicated compliance with Lipinski drug-likeliness rule (score À0.55). ADMET prediction showed strong plasma protein binding, GI absorption (Caco-2 cells permeability = 46.74 nm/s), blood brain barrier penetration (Cbrain/Cblood = 0.31), efflux by P-glycoprotein, metabolism by CYP1A2, CYP2C19 and CYP3A4, medium hERG inhibition and non-carcinogenicity in rodents. Predicted molecular targets included mainly receptors (glucocorticoid, kappa opioid, delta opioid, adrenergic and dopamine), oxidoreductase (arachidonate 5-lipoxygenase and cyclooxygenase-2), enzymes (HMG-CoA reductase) and kinase (NFjb). Withametelin was more cytotoxic to cancer cells (DU145 IC 50 7.67 ± 0.54 mM) than normal lymphocytes (IC 50 33.55 ± 1.31 mM). It also showed good antioxidant and protein kinase inhibition potentials. Furthermore, withametelin (20 mg/ kg) significantly reduced inflammatory paw edema (68.94 ± 5.55%), heat-induced pain (78.94 ± 6.87%) and immobility time (50%) in animals. Molecular docking showed hydrogen bonding interactions (bind-ing energies: À11.3 to À7.8 kcal/mol) with arachidonate 5 lipoxygenase, NFjb and glucocorticoid receptor. Withametelin has potential for advance investigations for its cytotoxic, anti-inflammatory, analgesic and antidepressant activities. Ó 2020 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
... Active ingredients present in Ashwagandha can reduce stressinduced damage, and do not influence the normal body functions much (35). Several studies have demonstrated the beneficial effects such as anti-stress, anxiolytic, and antidepressant effects of Ashwagandha in both humans and animal models (36)(37)(38). A study done in geriatric dogs with hepatic dysfunction showed a significant increase in total protein concentration after 14 days of treatment with Withania somnifera extract (39). ...
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Ashwagandha (Withania somnifera L. Dunal.) is an important “Rasayana” of Ayurveda. The roots are extensively used as an adaptogen and for different health issues. Anti-inflammatory, antioxidant, and immune-stimulating effects of Ashwagandha are well-documented. The present study aimed to evaluate the clinical efficacy of Ashwagandha root extract as an adaptogen against various types of stress in horses. A total of 24 Kathiawari horses were selected and randomly divided into four groups. All the horses were provided with normal feed and water ad libitum. Group 1 (G1) was treated as the control group, and the horses were given a normal diet. Group 2 (G2), Group 3 (G3), and Group 4 (G4) horses received varying doses of Ashwagandha root extract along with the normal diet. All the animals were subjected to different types of stress including exercise-induced stress, separation, and noise stress on three different days and evaluated for various hematological, biochemical, hormonal, and immunological parameters. Over the 21 days, a statistically significant (p < 0.05) increase in total erythrocyte count, total leucocyte count, hemoglobin content, lymphocyte percentage, reduced glutathione, and superoxide dismutase activities was observed. A statistically significant (p < 0.05) decrease in cortisol, epinephrine, glucose, triglycerides, creatinine, IL-6, alanine aminotransferase, and aspartate aminotransferase was observed in the Ashwagandha treated groups (G2, G3, and G4) when compared to the control group (G1). The results suggest that Ashwagandha root extract has potent hemopoietic, antioxidant, adaptogenic, and immune-stimulant properties. Keywords: horses, stress, Ashwagandha root extract, adaptogen, cortisol, IL-6 3, Ashwagandha (Withania somnifera)
... Our results showed increased proliferation of lymphocyte normal cells after These results agreed with previous studies which showed that Ashwagandha has powerful anti-oxidant action as it increased the levels of three natural anti-oxidants; superoxide dismutase, catalase, and glutathione peroxidase in the rat brains [34]. Moreover, agreed with Andallu and Radhika who reported that Ashwagandha is as an important medicinal plant that has good antioxidant potentials throughout its root [35]. ...
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Objective: Evaluation antiviral effects of Withania somnifera (Ashwagandha) leaf extract against HCV. Methods: cell proliferation was assessed using MTT assay after isolation of lymphocyte cells and treated with Ashwagandha water extract (ASH-WX) (6.25 mg/ml - 100 mg/ml). Assessment of quantitative Real-time PCR, Colony forming assay, TNF-α and molecular docking studies after infection of normal lymphocyte cells with 1 ml (1.5 × 106 HCV) serum then incubated with ASH-WX at concentration 25 mg/ml & 50 mg/ml. Results: MTT assay revealed a significant increase (p < 0.001) in normal lymphocyte proliferation at all concentration’s particularity at 25 mg/ml with SI (6.06) and at 50 mg/ml with (5.8). While TNF-α significantly decreased following ASH-WX treatment compared with control untreated infected cells (p < 0.05). PCR results showed a marked viral load reduction after treatment by ASH-WX at concentration 25 mg/ml to 6.241 × 103 IU/mL. Colony formation assay test revealed colony formation reduction compared to positive untreated control. Molecular docking analysis revealed good prediction of binding between Ashwagandha and NS5B and PKN2 compared to Sovaldi. Conclusion: ASH-WX may be a powerful antiviral against HCV infection.
... Withania somnifera, referred to as Aswagandha in the Indian system of medicine, is a central nervous system active herb that has been used for various neurological disorders. Studies with W. somnifera have indicated that it exerts an antiaging effect anxiolytic and antidepressant activity [216]. The other pharmacological actions exerted by W. somnifera include anti-inflammatory, antistress, hemopoietic immunomodulatory, and antioxidant effects [217][218][219]. ...
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Cerebrovascular diseases are the leading cause of mortality and morbidity worldwide. These diseases pose many clinical challenges and even experienced clinicians can arrive at the point where work-up, treatment, or prognostic thinking falters. This book will highlight the latest trends in preventive and treatment measures regarding patients prone to or suffering from stroke, embolism, thrombosis, hemorrhage, and other critical cerebrovascular ailments. While progress has been made in prevention and supportive care, efforts to protect the brain from cell death have not succeeded completely hence, no new treatment has made it from bench to bedside since tissue plasminogen activator was introduced some 18 years ago. Thus there is urgent challenge before the scientific fraternity to come up with new ideas and ways to treat stroke and protect brain from cell death. Most therapeutic approaches developed in the laboratory have focused on protecting neurons from the main pathogenic mechanisms causing ischemic injury, such as excitotoxicity, oxidative stress, inflammation or apoptosis. These experimental treatments have shown some progress in large clinical trials, an outcome that has sparked a lively debate about the promise of neuroprotection in stroke therapy. Unlike traditional therapeutic approaches based on counteracting selected pathways of the ischemic cascade, endogenous neuroprotection relies on coordinated neurovascular programs that support cerebral perfusion, mitigate the harmful effects of cerebral ischemia and promote tissue restoration. Understanding how the brain triggers and implements these protective measures may advance our quest to treat stroke and open a new era in stroke therapeutics. Here in this book we will describe different modalities by which the brain protects itself, aiming to provide a synthesis of the different mechanisms and highlighting their potential relevance for the future of stroke therapy. Leading-edge scientific research from across the globe and the possible mechanisms involved in treatment of stroke will be presented in this book to the audience. Finally we will focus on the role of different medicines and the natural herbs in the prevention and treatment of Cerebrovascular Diseases with focus on stroke. Further the book will highlight the recent trends in the ongoing research in stroke and cerebrovascular diseases. The book will highlight the latest trends observed in the Immunobiology of cerebrovascular diseases and Stroke. The recent advancements in understanding the inflammatory and oxidative stress mechanisms in stroke and other cerebrovascular diseases. Here we will discuss the currently available medicines with importance and side effects. Recent advancements in the Stroke therapy and finally the natural herbs in the treatment of cerebrovascular diseases of Stroke and how we can prevent the cerebrovascular diseases and stroke from occurring by using these herbs in food and as a preventive medicine. Moreover upto date latest trends in the research will be included in the book with many flowcharts and diagrams to make it a success.
... Shirodhara and shiropichu are the transcranial route of drug delivery and a study has shown the possibility to deliver central nervous system drugs through the brain-targeted transcranial route when applied on the scalp in an oil-solubilized dosage form [23,24]. Few of the oral medications and their ingredients have demonstrated psychotrophic action. Manasamitravataka is effective against GAD [21], while Ashwagandha has anxiolytic and anti-depressant activity [25]. Few drugs like vacha [26], jatamamsi [27], brahmi [28], and shankhapushpi [29] have demonstrated anti-depressant activity. ...
Article
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Major Depressive Disorder (MDD) is a chronic, episodic disorder which manifests with disturbance in mood, interest, cognition and vegetative symptoms. It has major impact on quality of life of the patients, affecting physical, mental, personal, social, and spiritual well-being of the patient. Vishada and avasada represents minor depressive episodes and MDD can be equated to Kaphaja Unmada. Current case presented with sadness, worthlessness, helplessness, death wishes, disturbed sleep and was diagnosed as MDD as per DSM V criteria. Ayurveda diagnosis was Kaphaja Unmada involving kapha-dominant vata dosha, and tama dosha. Mental examination revealed derangement of mana (mind), buddhi (intellect), smruti (memory), bhakti (desire), sheela (temperament), chesta (psychomotor activity) and achara (conduct) components. Patient was Avara Satwa. Management was planned with integrative treatment comprising of Yukti vypasharaya (pharmacological), Satwawajaya (counselling) and daiwivyapashraya (spiritual-based techniques). Management was with snehapana (internal oleation), virechana (gut cleansing), sarvanga abhyanga (massage of whole body with medicated oil) followed by bashpa sweda (steam therapy to whole body), shirodhara (dripping of medicated oil on fore head), shiropichu (transcranial drug administration by placing cotton pad dipped in medicated oil), katibasti (holding of medicated oil in well prepared from dough), satwavajaya chikitsa, and daiwi vyapashraya chikitsa. Conventional psychopharmacological interventions taken since last year were tapered and discontinued. Treatment continued for 352 days which included 13 days of hospitalized treatment and follow-ups. Intervention outcome showed reduction in Hamilton depression Rating scores getting reduced from 31 to 6. Patient's self-assessed worry reduced from 16 h/day to 2 h/day, self-assessed daily relaxed state improved from ½ hour/day to 14 h/day. Patient showed complete remission by 180th day of intervention. Improvements sustained even during the non-interventional observation period. Ayurvedic integrative management showed effective in management of MDD.
... Similarly, Withania somnifera (Solanaceae) is known for its pharmacological applications since ancient times. Several studies have reported the efficacy of W. somnifera as an antimicrobial, antioxidant, and antiinflammatory agent [52]; antidepressant [53]; and for anticancer activities [54]. The leaf extract of W. somnifera leaves contains several secondary metabolites such as alkaloids, anthocyanin, flavonoids, and other polyphenols, which are known to have antimicrobial activities [55]. ...
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This study is aimed to cost-effectively produce bacterial cellulose (BC) and impart it with antimicrobial activity by introducing bactericidal plant extracts into its three-dimensional matrix through an ex situ modification strategy. Briefly, the fruit wastes were utilized as the carbon source for BC production by Gluconacetobacter hansenii, followed by impregnation of bioactive extracts of Anogeissus dhofarica and Withania somnifera plants. FE-SEM and FTIR analyses showed the successful synthesis of BC-Anogeissus dhofarica (BC-A) and BC-Withania somnifera (BC-W) composites. Both BC-A and BC-W composites held 87% and 75% water of their dry weight, respectively, and each composite retained about 50% of originally absorbed water after 24 h. The bactericidal activities of BC-A and BC-W composites were investigated against Staphylococcus aureus and Escherichia coli as model Gram-positive and Gram-negative pathogens, respectively. Both BC-A and BC-W composites showed impressive antibacterial activity against S. aureus by producing a clear inhibition zone of 13 mm and 6 mm, respectively. Although no clear inhibition zone was observed against E. coli, both composites reduced its growth up to 50% of its live cell density. This is the first report of exploring the antibacterial activities of A. dhofarica and W. somnifera plant extracts and developing their composites with BC, which could be of vital importance for natural products and biopolymer researchers to develop biomedical materials. Graphical abstract ToC. Low-cost production and ex situ impregnation of bioactive plant-extract into bacterial cellulose matrix showing antibacterial activity.
... Withania somnifera glycowithanolides exhibited an antidepressant activity, comparable to imipramine, in the forced swim-induced 'behavioral despair' and 'learned helplessness' tests. This study showed that Withania somnifera has antidepressant activity 19 . ...
... Withania somnifera, popularly known as Ashwagandha, is an important medicinal plant that has been around for over 3,000 years in Ayurveda and indigenous medicine. The dried powder, crude extract, and purified phytochemicals of this medicinal plant have shown promising therapeutic qualities [3]. The main metabolites responsible for the plant's therapeutic qualities are withanolides. ...
Chapter
Withania somnifera, popularly known as Ashwagandha, is an important medicinal plant that has been around for over 3,000 years in Ayurveda and indigenous medicine. It is one of the most significant herbs in Ayurveda (India's traditional medical system), and it has been utilized as a Rasayana for millennia for its wide-ranging health effects. The main metabolites responsible for the plant's therapeutic qualities are withanolides. It has a wide range of pharmacological qualities for application in biological methods, including antibacterial, antiinflammatory, antistress, anticancer, neuroprotective, cardioprotective, and many more. Ashwagandha has a vast range of chemical components, including alkaloids, ergostane steroids, amino acids, and neurotransmitters, which explains its extensive range of therapeutic characteristics, which can prevent and treat a variety of diseases directly or indirectly. Various parts of the Ashwagandha plant, such as the roots and, less frequently, the leaves and fruits, have been utilised as plant- derived remedies. For generations, the extract prepared from the roots of Withania somnifera has been considered to have potent properties like promoting energy and vitality.
... • According to study, ashwagandha increases the growth of axons and dendrites and the quantity of antioxidants in the brain (17). • Numerous mouse studies demonstrated that Ashwagandha exhibited memory-enhancing, anti-anxiety, antidepressant, and testosterone-like properties (18)(19)(20). ...
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Cognitive enhancement is defined as the augmentation of the mind's core capabilities through the improvement of internal or external information processing systems. Recently, the focus has shifted to the potential therapeutic effects of natural products in improving cognitive function. Edible bird's nest (EBN) is a natural food substance derived from the saliva of swiftlets. Until today, EBN is regarded as a high-priced nutritious food with therapeutic effects. The effectiveness of dietary EBN supplementation to enhance brain development in mammals has been documented. Although the neuroprotection of EBN has been previously reported, however, the impact of EBN on learning and memory control and its potential as a cognitive enhancer drug remains unknown. Thus, this article aims to address the neuroprotective benefits of EBN and its potential effect as a cognitive enhancer. Notably, the current challenges and the future study direction in EBN have been demonstrated.
... Ashwagandha roots and extracts are used to make herbal teas, powders, pills, and syrups that aid in the reduction of arthritis, disability, weariness, high cholesterol, and stress, accelerate healing processes, combat impotence and balance blood sugar levels. The alkaloids and steroidal lactones with anoides found in the roots, leaves, and fruits (berry) have antiinflammatory (Anabalagan and Sadique, 1984), anti-arthritis (Begum and Sadique, 1988) and immunosuppressive activities (Singh and Kumar, 1998), antioxidant (Dhuley, 1998), immunomodulatory (Davis and Kuttan, 2000), and antidepressant properties (Bhattacharya et al., 2000). For the supply of tuberous roots for forskolin and withafarin, the pharmaceutical businesses rely mostly on the wild population of Ashwagandha. ...
... Withanone (Pandey et al. 2018), ashwagandhanolide (Subbaraju et al. 2006) Anxiolytic, antidepressant (Bhattacharya et al. 2000), antioxidant (Dhanani et al. 2017), antistressor (Archana and Namasivayam 1998), adaptogenic (Bhattacharya and Muruganandam 2003) project, documented information from the Marma community of the studied area will be deposited at the e-repository <www.mpbd.info> for the general people and outcome of the project will be explained to the informants of the studied area. ...
Article
The ethnomedicinal practices of Marma indigenous community of Bangladesh is considered rich. This study aimed to compile their medicinal plant usage to get fresh insights into newer ethnobotanical uses. Ethnomedicinal information was collected through open-ended/semi structured techniques following field interview, plant interview and market survey from key informants. Documented data was further analyzed using different quantitative indices. The Jaccard index was also calculated to show the degree of similarity with previous studies conducted in Bangladesh and abroad. A total of 196 plants from 75 families belonging to 164 genera were documented in the survey. Gastrointestinal disorders epitomized the foremost complaints sort with the use of 72 plant species, followed by pain and inflammation (63 species). Leaves (42.8%) were the principal source of medication while trees were the major plant type used in the ethnobotanical practice. The original application of ethnomedicinal plants within our study was compared with 44 previous ethnomedicinal research studies and the Jaccard index (JI) ranged from 0.78 to 46.78. The highest similarity within the country was recorded with studies from the Bandarban district while the lowest was from the northern region. Similarly, the highest similarity with reports from neighboring countries was with Chanduali district of UP, India and the lowest with FATA, Pakistan. Importantly, our literature study exhibited that this study recorded 23 species with new ethnomedicinal uses. The Marma community still depends on plants to treat different complaints/diseases. This compilation may provide a future resource for further phytochemical and pharmacological studies.
... Traditionally, topical application of the berries and leaves of this plant is used as a remedy for ulcers and tumors [7]. Apart from that, it also showed anti-stress [21,22], anti-inflammatory [23][24][25][26][27], anti-oxidant [24,[28][29][30], and anti-depressant [31,32] properties [33][34][35][36]. Withanolides, with 28 carbons of naturally occurring steroids, are the main chemical constituents of the Withania genus [37]. ...
Article
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Natural products are a major source of biologically active compounds that make promising lead molecules for developing efficacious drug-like molecules. Natural withanolides are found in many flora and fauna, including plants, algae, and corals, that traditionally have shown multiple health benefits and are known for their anti-cancer, anti-inflammatory, anti-bacterial, anti-leishmaniasis, and many other medicinal properties. Structures of these withanolides possess a few reactive sites that can be exploited to design and synthesize more potent and safe analogs. In this review, we discuss the literature evidence related to the medicinal implications, particularly anticancer properties of natural withanolides and their synthetic analogs, and provide perspectives on the translational potential of these promising compounds.
... Withania somnifera glycowithanolides exhibited an antidepressant activity, comparable to imipramine, in the forced swim-induced 'behavioral despair' and 'learned helplessness' tests. This study showed that Withania somnifera has antidepressant activity 19 . ...
... In a 60-day experimental study in stressed adults, those who took 600mg/day reported a 79% reduction in severe depression. At the same time, the placebo group reported a 10% increase (Bhattacharya et al., 2000). (Harikrishnan et al, 2008) investigated the influence of W. somnifera root powder on the levels of circulatory ammonia, urea, lipid peroxidation products such as TBARS (thiobarbituric acid and reactive substances), HP (hydroperoxides), and liver marker enzymes such as AST (aspartate transaminase), ALT (alanine transaminase) and ALP (alkaline phosphatase), for its hepatoprotective effect in ammonium chloride-induced hyperammonemia. ...
Chapter
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This chapter is about the Medicinal plant Ashwagandha.
Article
Lifestyle Disorders (LSD) are common problems among upper-middle and higher society children. Lifestyle has long been associated with the development of many chronic diseases. It affects both genders. WHO has recognized Noncommunicable diseases (NCDs), especially diabetes, obesity, cardiovascular disease, cancer, and chronic lung disease, have everyday lifestyle linked risk factors like lack of physical activity, unhealthy diet and feeding habits and harmful use of alcohol. Worldwide, the current scenario of NCDs is the primary cause of morbidity and mortality, even in young children. According to WHO Report 2004, these account for nearly 60% of deaths and 47% of the global burden of illness. The rise in NCDs is substantially accelerating in most developing countries like India. In India, 53% of the deaths in 2008 were due to NCDs, and cardiovascular disease (CVDs) alone accounted for 24% of deaths (WHO). In 2005 India experienced the highest loss in potentially productive years of life globally, and the leading cause of death was cardiovascular disease. The cumulative loss of national income for India due to NCDs mortality for 2006-2015 was around USD237 billion. By 2030, this productivity loss is estimated to double to 17.9 million years lost. These major NCDs are preventable through effective Ayurvedic interventions by judiciously treating lifestyle-related modifiable risk factors. This review confers the current scenario of NCDs in children and their Ayurvedic Management.
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The majority of the population in Bangladesh uses traditional plant-based medicines to manage various ailments, including central nervous system (CNS) disorders. This review presents ethnobotanical information and relevant scientific studies on plants used in traditional healthcare for the management of various CNS disorders in Bangladesh. The information on the medicinal plants of Bangladesh effective against CNS disorders published in scientific journals, books, and reports was compiled from different electronic databases using specific key words. The present article provides comprehensive information on a total of 224 medicinal plant species belonging to 81 families used for the treatment of CNS disorders by the various peoples of Bangladesh. In total, we reviewed more than 290 relevant papers. In this study, leaves were found as the most often used plant organ, followed by roots, fruits, whole plants, barks, seeds, stems, rhizomes, and flowers. The Fabaceae family contributes the highest number of used species, followed by Rubiaceae, Lamiaceae, Cucurbitaceae, Vitaceae, Euphorbiaceae, Malvaceae, and Zingiberaceae. The most frequently used species (in decreasing order) are Asparagus racemosus, Centella asiatica, Stephania japonica , Aegle marmelos, Coccinia grandis, Tabernaemontana divaricata , Bacopa monnieri , Abroma augusta, and Scoparia dulcis . This review may serve as a starting point for a rational search for neuroactive natural products against CNS disorders within the Flora of Bangladesh. Graphic Abstract
Article
Background Prevalence of psychiatric disorders such as anxiety is a very common and affecting many people all around the world. Currently, many synthetic pharmacological products/ drugs are available in the market to cure the disorder, but associated with various adverse reactions or side effects which may cause discomfort and sometimes other disorders to the patients. In the past years, use of complementary and alternative medicine has increased. The exploration in the areaof herbal psychopharmacology has received much attention as people are using more herbal treatment to benefit their health. Objective To provide a comprehensive information on anxiety disorder and its herbal treatment Method In this review, we enlisted the plants, plant extracts and isolated component (if any) along with models used to explore anxiolytic property; in retrospect, still a lot of research required to establish them clinically. Result Literature revealed that a variety of medicinal plants are effective for the treatment of anxiety likeGinkgo biloba, Passiflora incarnata, Gelsemium sempervirens, Piper methysticum, Bauhinia variegate, Matricaria recutita, Brassica oleracea, Hypericum perforatum, Echium amoenum, and Scutellaria lateriflora. Conclusion Exploration of herbal plants may be beneficial to establish more potential compounds for treatment of anxiety disorders.
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The effect of Withania somnifera a medicinal plant seed extract was tested against lesser mulberry pyralid, a potential pest of mulberry. The mulberry leaves were used for silk production in rural areas of northern Iran. The extract was administered orally by leaf dipping method in two lower (5%W/V) and higher (15%W/V) dosages to third instar larvae (<24 h) for biological assays and to fifth instar larvae (<24 h) for Physiological studies. The results showed formation of larvoids (Ls), larval-pupal intermediates (LPIs), pupoids (Ps) and pupal-adult intermediates (PAIs). The results showed increased larval duration by 1.7 and 2 folds in 5 and 15% treatment, respectively. Fecundity of resultant adults was decreased by 1.2 and 1.3 in 5 and 15% treatment, respectively. Except approximate digestibility (AD) and consumption index (CI) all other feeding indices showed reduction. The feeding deterrence was prominent at 15% (87%) and 5% showing 48% deterrence. Our enzymatic and non-enzymatic assessments upon treatment showed reduction in key components, except detoxifying enzymes. However, the activity of an important enzyme involved in cuticle hardening and immunity called phenoloxidase was reduced. We also investigated the histology of midgut for further analysis and found drastic changes in main cellular elements. Immunological changes following treatment was noticeable in reduced Total Hemocyte Count but surprisingly increased Differential Hemocyte Count. However, the hemocytes structure was extremely damaged. The reduced number of eggs in treated but survived adults indicated reduced ovaries, with vacuolization both in trophocytes and oocytes. The key chemical compounds showed reductions particularly at 15%. The present results are concomitant with few earlier studies on this medicinal plant and deserve further studies particularly in deriving key chemicals that alter metamorphosis similar to insect growth regulators.
Research
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Ashwagandha, scientifically known as Withania somnifera Dunal, is an important medicinal plant in the Ayurvedic system of medicine. The roots are highly valued and are used either alone or in combination with other medicinal plants to treat a variety of ailments. It is also used as a general tonic, to increase and to improve the overall health and longevity. Regular consumption of ashwagandha is believed to prevent diseases in individuals of varied ages and health conditions. Preclinical studies have shown that Ashwagandha Rasayana possesses radioprotective effects and reduces the radiation-induced emaciation, decrease in the organ weight and to decrease radiation-induced increase in serum transaminase levels. The body weight along with the levels of hemoglobin, red blood cells, white blood cells, and platelets was restored. Aswaghandha is consider to be the nature gift to mankind, it has a potencial significance for targeting the cancerous compounds present in body. Therefore, it is interested to dock Aswaghandha against vimentin protein found in humans (Homo sapiens) with the help of molecular docking tool autodock vina which not only helps in discovering of drugs but also shows the virtual screening, high performance and enhanced accuracy of the drugs.
Article
Ethnopharmacological relevance: Withania somnifera (L.) Dunal (WS), a known 'Rasayana' (rejuvenating agent) as per Ayurveda is prescribed to promote health, to increase longevity and to hasten recovery in disease convalescent stages. Among its other uses, WS is specifically recommended in Ayurveda for central nervous system related disorders. WS has demonstrated protective effect on alcohol dependence and withdrawal anxiety in previous experimental studies. Aim of the study: To evaluate effect of WS on conditioned place behavioral paradigm (model of relapse) and on GABA and dopamine levels in critical brain areas. Methodology: Following Animal Ethics Committee permission, the mice (n = 24) were divided into the following study groups for experiment 1,: 1 -distilled water, 2 -WS and 3 -Naltrexone. They were conditioned on conditioned place preference (CPP) using alcohol (2 gm/kg)/saline administered intraperitoneally for 8 days. WS and Naltrexone were administered during the period of extinction (6-8 days). Effect of WS on reinstating behaviour of rats (time spent in alcohol paired compartment) primed with alcohol injection was noted. Effect of WS (450 mg/kg/) on GABA and dopamine levels from rat midbrain, striatum and cortex (ng/gm) were measured in alcohol dependent rats (n = 30) following the first phase of standardisation assay. The rats (n = 24) were made alcohol dependent for 15 days (intermittent access model) and WS was administered concurrently. Levels were measured on Day 16. Results: WS group showed decrease in time spent in alcohol paired compartment alike Naltrexone but it differed significantly from control (p < 0.05). Alcohol-dependent rats showed decrease in GABA and increase in dopamine in alcohol alone group vs distilled water. WS administration showed rise in GABA and fall in dopamine in all brain parts (p < 0.05 vs control). Conclusion: Withania somnifera protected animals from relapse and showed beneficial effects on the neurotransmitters implicated in alcohol dependence. The study provides substantial evidence for its potential application in alcohol use disorder.
Article
PROMISCUOUS OR DIRTY DRUG WITH MULTIFUNCTIONAL DRUGGABILITY NATURE OF CURCUMIN (CURCUMA LONGA LINN.); REPURPOSING IN PROPRANOLOL WITHDRAWAL-INDUCED OCD RELATED ANXIETY: A PROMISING DRUG DISCOVERY BESIDES ONE-DRUG-ONE-RECEPTOR APPROACH VIA IN SILICO IN VIVO STUDIES. ABSTRACT: Background: Curcumin (Curcuma longa) and propranolol display a plethora of pharmacological activity linked with multifunctional druggable nature designated as a promiscuous or dirty drug (magic shotguns) that hit 'on-target as well as 'off-target' (anti-target). Multifactorial origins, with complex neuronal networks and broad-spectrum symptomatology, operates most CNS disorders. Anxiety is one of the comorbidities in the psychogenic spectrum of obsessive-compulsive disorder (OCD). The present study of OCD has been based on its multifunctionality and diverse drug potential, tailoring together the morbidity and comorbidity patterns of OCD. Very few multimodal drugs did trial in this regard, which has multifunctional druggability, except selective serotonin reuptake inhibitors (SSRIs) that work via the one-drug-one-receptor-one-disease approach; however, with inter-individual variability, unwanted side effects and limited multifunctionality with the druggable targets. SSRI success rates in OCD and its related disorder are minimal, especially in the adversity of comorbidity pattern. Objective: The principal objective of the current research was to testify the multifunctional druggable plethora of curcumin via repurposing of its dirty drug nature to reverse the obsessed anxiety of propranolol withdrawal-induce mice, besides the "one drug one receptor" approach or magic bullet. Methods: The present study evaluated OCD related anxiety-like behavior after different periods of abstinence (24 h, 7 and 21 days) from repeated propranolol (10 mg/kg) administration in mice. In addition, we also examined the action of curcumin (EERCL-50 mg/kg) and fluoxetine (20 mg/kg) for the attenuation or reversal of OCD related anxiety-like behavior after seven days to 24 hours propranolol withdrawal. The initial stage of the hypothesis toward the target of curcumin was identified via in-silico using SwissADME drug-likeness study, followed by in-vivo studies using Swiss albino mice. Evaluation for the same did use elevated plus maze (EPM), marble-burying behaviour (MBB) and motor activity (MA) test as a model. Further, did also investigate the antioxidant activity. Result: The result revealed a decrease in all parameters 24 hours and 14 days after exposure to propranolol, indicating anxious behaviour. The administration of curcumin and fluoxetine after 24 hrs of abstinence reduced animal anxiety in EPM; after the abstinence periods, the drug reduced the MA in the MBB. Curcumin reversed the anxiogenic effect induced by propranolol in EPM. The value of p<0.05 was considered statistically significant. Conclusion: Results revealed that propranolol might, to a large extent, impart to withdrawal-induced obsessed anxiety, and curcumin could effectively treat propranolol dependent obsessed mice. Further, curcumin anti-compulsive competency substantially showed promising success besides one drug-one receptor-one disease approach or magic bullet. Keywords: Dirty drug Druggability Repurposing Scattergun one drug-one receptor Curcumin Multifunctional OCD multimodal drug drug discovery. Cite this article: Rahul Kumar Mishra, Ashutosh Mishra, Amresh Gupta. Promiscuous or Dirty drug with Multifunctional Druggability nature of Curcumin (Curcuma longa Linn.); Repurposing in propranolol withdrawal-induced OCD related Anxiety: A promising drug discovery besides One-Drug-One-Receptor approach via in silico in vivo studies. Research Journal of Pharmacy and Technology. 2022; 15(7):2898-8. doi: 10.52711/0974-360X.2022.00484" https://rjptonline.org/AbstractView.aspx?PID=2022-15-7-6#:~:text=ABSTRACT%3A%0ABackground,0974%2D360X.2022.00484
Article
Background Obsessive compulsive disorder (OCD) is a potentially debilitating diseases which affects 1-4% of the general population. It is characterized by the presence of obsessions and compulsions which interfere with the individual’s life and functioning. Although conventional treatments such as drug therapies and cognitive behavioral therapy exist for OCD, these treatments are not universally successful and can cause side effects, which has created a demand for alternative and complementary therapies. Methods In this review, we summarize randomized clinical trials on effectiveness of herbal medicines for treatment of OCD, and review the possible mechanisms of action for these medicines. A search in Pubmed, Scopus, and The Cochrane Library found 1022 studies, of which 7 were included in our review. Results The studies that we found were conducted over 6 to 12 weeks, and had an average sample size of 37. The plant species studied included Crocus sativus, Echium amoenum, Hypericum perforatum, Silybum marianum, Valeriana officinalis, and Withania somnifera. The trials demonstrated the effectiveness of all plants as treatments for OCD except H. perforatum. The phytochemicals found in these plants produce their effects through a variety of means such as inhibiting the reuptake of monoamines, GABAergic effects, and neuroendocrine modulation. The small number of studies and their small sample sizes, poor methodology, and lack of replication highlight the need for further research into herbal medicines for treatment of OCD. Conclusion Overall, herbal medicines can be used as stand-alone therapies for OCD or in conjunction with other methods.
Article
Withania somnifera (L.) has long been used as a traditional rasayana herb against a variety of human ailments. This research presents a high performance thin layer chromatography based chemo profiling of Ashvagandharishta and its antidepressant activity. The in-house formulation was made using a fermentation process according to the Indian Pharmacopoeia. Physiochemical standardization of the formulation was performed using different quality control parameters such as total ash, acid insoluble ash, alcohol soluble extract value and water soluble extract value. A column chromatography and high performance thin layer chromatography method was used to isolate and estimation of withanolide-A, withaferin-A & β-sitosterol from the root of W. somnifera. In addition. The antidepressant effect of different formulations were carried out by force swimming test in albino mice. The thiobarbituric acid reactive substances (TBARS) and Glutathione (GSH) assay was used to find out the oxidative stress. W. somnifera root has been standardized macroscopically, microscopically, physico-chemically according to the guidelines of the Ayurvedic Pharmacopoeia. The qualitative and quantitative analysis was performed using high performance thin layer chromatography and it was performed on each formulation and found the content of withanolide-A and -sitosterol in the in-house formulation is higher while withaferin-A is rather contained in the decoction. The antidepressant effect showed that the immobility time was lowest in the case of the standard formulation followed by in house formulation, while the increase in glutathione and the reduction in thiobarbituric acid reactive substances levels revealed the antioxidant nature of the formulation. In conclusion, based on the above results, we can conclude that Ashvagandharishta could be a breakthrough for the treatment of depression in the future.
Article
Ethnopharmacological relevance: Withania somnifera (L.) Dunal (Physalis somnifera L.) is a fairly known perennial shrub of Solanaceae family, and is used in Ayurveda- Traditional Indian Medicine (TIM), since ancient times. It is well known as Ashwagandha in Sanskrit language in Ayurvedic classics. Its Mula (root) is recommended for health and healing, and the number of single and compound formulation is prescribed rationally. It is believed that the species name-somnifera is coined based on popular use to "induce sleep" in Ayurveda. Aim of the study: The present study was aimed to bring out the experience-based traditional uses of Ashwagandha for health and healing with an emphasis on the pharmacological and biochemical scientific evidences to corroborate them. The scientific evidences have been explored from the national and international publications. Materials and method: A comprehensive literary search of Ayurvedic classics was carried out systematically regarding Ashwagandha for its rationality behind the traditional uses. To excavate the subject matter, the original Ayurvedic scriptures and several standard Ayurvedic texts of different period was studied insightfully for meaningful contribution. It is to be noted that the primary source of knowledge was considered in writing this manuscript without any biased attitude. The available literature on Ashwagandha was also searched to ascertain the basis of scientific Latin name and correct identity. The Ayurvedic Pharmacopoeia and other relevant scientific works were also taken into consideration to make the subject matter more clearly to the scientific world. For the scientific evidence of the uses, the international and national Journals and other published material were also searched to make it inquisitiveness to the scholars interested in Ayurvedic medicinal plants. Results: The present paper throws ancient luminosity behind the therapeutic uses of one of the promising plant drug i.e., Ashwagandha of ancient India even to the present time. The scientific evidences corroborate the rationality ascribed in available Ayurvedic classics of various period of India has been gained. Conclusion: The study explores that the first reference of Ashwagandha with its significant nomenclature, useful part, properties, action, and eloquent uses has its footprint in the original texts of Ayurveda. In later works enhanced knowledge with traditional uses continued even today. Several single and compound formulations have been found to maintain the health and to alleviate the disorders rationally. It is worthy to note here that the scientific evidences corroborate the uses practiced in Ayurveda.
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Depression is the most common of the affective disorders (disorders of mood rather than disturbances of thought or cognition); it may range from a very mild condition, bordering on normality, to severe (psychotic) depression accompanied by hallucinations and delusions. Worldwide, depression is a major cause of disability and premature death. Unipolar depression is commonly (about 75% of cases) non-familial, clearly associated with stressful life-events and accompanied by symptoms of anxiety and agitation; this type is sometimes termed reactive depression. Other patients (about 25%, sometimes termed endogenous depression) show a familial pattern, unrelated to external stresses, and with a somewhat different symptomatology. This distinction is made clinically, but there is little evidence that antidepressant drugs show significant selectivity between these conditions.
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The various antianxiety drugs currently used cause numerous adverse drug reactions. Though in the late seventies some work was done on Withania coagulans, it is the vulnerable species not found plentiful. Therefore, it was worthy to investigate the anxiolytic actions of alcoholic extract of Withania coagulans fruits in Swiss albino mice by using Elevated Plus Maze (EPM) test. To study the antianxiety activity of alcoholic extract of Withania coagulans fruits in Swiss albino mice by Elevated Plus Maze (EPM) test. The antianxiety activity was measured using Elevated Plus Maze (EPM) test. The antianxiety drugs promote the mice to spend more time in open arm and less time in close arm. This increase in the time spent in the open space as well as number of entries from close to open space was correlated statistically with control and standard in the EPM test. One way ANOVA was used for the statistical analysis. Time spent in the open arm (Open) as well as number of entries into the open arm (EOA) by the Swiss albino mice was statistically highly significantly (p-value < 0.001) associated with the alcoholic extract of Withania coagulans fruits in Elevated Plus Maze (EPM) test. The alcoholic extract of Withania coagulans fruits established the antianxiety activity in Swiss albino mice by Elevated Plus Maze (EPM) test.
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Parkinson’s disease (PD) is a progressive neurodegenerative disease which affects millions of population worldwide. It is characterized by motor symptoms such as excessive tremor, bradykinesia, rigidity, postural instability and non-motor symptoms include neuropsychiatric complications like anxiety, depression, insomnia and cognitive impairment, orthostatic hypotension, sexual dysfunction and gastrointestinal complications. Treatment of anxiety in PD poses extensive challenge to global healthcare which makes it urgent to develop innovative treatment for the better management of the disease. The gold standard treatment by Levodopa provides symptomatic relief and its effect on neuropsychiatric complications like anxiety is elusive. Presence of anxiety worsens the condition and challenges therapeutic management of the PD. The in-depth analysis and understanding the molecular mechanism and pathophysiological pathways associated with the onset of anxiety in PD is essential. The disturbances in serotonergic, adrenergic and GABAergic neurons and hypothalamic pituitary adrenal axis play a significant role in the pathophysiology of anxiety. The drugs like Selective Serotonin Reuptake Inhibitors, tricyclic antidepressants and benzodiazepines are useful in the management of anxiety but due to severe side effects and progression of the disease it results in the failure of treatment. The present review imparts an insight in the management of anxiety in PD by understanding molecular mechanism and application of alternative treatment options which can enlighten the perception of researchers towards better therapeutic management of the disease.
Article
Background Anxiety, a familiar form of psychiatric disorder, influences numerous persons throughout the world. These psychological disorders frequently need an enduring regime of recommended medicines and impose huge costs on human societies. For the last few decenniums, discovery in the field of natural neurophysiology garnered a lot of recognition because of its least side effects. Objective Many people find it helpful to discover an effective herbal remedy for anxiety with fewer detrimental repercussions. The purpose of the present article is to report medicinal plant species used as anti-anxiety agents, which in turn, are helpful to develop new anti-anxiety herbal formulations. Method An unlimited, semantic electronic and manual exploration of PubMed, Cumulative Index of Nursing and Allied Health Literature, ISI, Google Scholar, Elsevier's abstract and citation database, and the database libraries was carried using keywords such as medicinal plants, herbal drugs, traditional medicine, and anxiety for recognizing natural medications in the management of anxiety disorders. Results Literary review collected the information of potential anti-anxiety plants. Data support the effectiveness of some popular herbal remedies by indicating high-quality scientific studies and support several clinically efficacious natural plants as anxiolytics. Conclusion Evidence-based studies indicate that natural plant treatment is an efficient way to manage anxiety disorders; the benefits outweigh the risks.
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Withania somnifera is a traditional Indian herb described under the ‘Rasayana’ class in Ayurveda, which gained immense popularity as a dietary supplement in the USA, Europe, Asia, and the Indian domestic market. Despite enormous research on the pharmacological effect of withanosides and withanolides, bioanalytical method development and pharmacokinetics remained challenging and unexplored for these constituents due to isomeric and isobaric characteristics. In current research work, molecular descriptors, pharmacokinetic, and toxicity prediction (ADMET) of these constituents were performed using Molinspiration and admetSAR tools. A rapid, selective, and reproducible bioanalytical method was developed and validated for seven withanosides and withanolides as per USFDA/EMA guidelines, further applied to determine pharmacokinetic parameters of Withania somnifera root extract (WSE) constituents in male Sprague Dawley rats at a dose of 500 mg/kg. Additionally, an ex vivo permeability study was carried out to explore the absorption pattern of withanosides and withanolides from the intestinal lumen. In silico, ADMET revealed oral bioavailability of withanosides and withanolides following Lipinski’s rules of five with significant absorption from the gastrointestinal tract and the ability to cross the blood-brain barrier. Upon oral administration of WSE, Cmax was found to be 13.833 ± 3.727, 124.415 ± 64.932, 57.536 ± 7.523, and 7.283 ± 3.341 ng/mL for withanoside IV, withaferin A, 12-Deoxy-withastramonolide, and withanolide A, respectively, with Tmax of 0.750 ± 0.000, 0.250 ± 0.000, 0.291 ± 0.102, and 0.333 ± 0.129 h. Moreover, at a given dose, withanoside V, withanolide B, and withanone were detected in plasma; however, the concentration of these constituents was found below LLOQ. Thus, these four major withanoside and withanolides were quantified in plasma supported by ex vivo permeation data exhibiting a time-dependent absorption of withanosides and withanolides across the intestinal barrier. These composite findings provide insights to design a clinical trial of WSE as a potent nutraceutical.
Article
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.
Article
Consideration and improvement for anxiety and depression are important during global pandemic diseases. Appropriate healthcare can be obtained by paying more attention to traditional medicinal sciences. The adverse effects of stress with its various symptoms can be managed by introducing plants that boost mental health. The most relevant psychological reactions in the general population related to global pandemic are pervasice anxiety, frustration and boredom, aspecific and uncontrolled fear, disabling loneliness, significant lifestyle changes, and psychiatric conditions. Ginseng, chamomile, passionflower, herbal tea, lavender, saffron, kava, rose, cardamom, Chinese date and some chief formula like yokukansan, Dan-zhi-xiao-yao-san, so-ochim-tang-gamiband, and saikokaryukotsuboreito are notable herbal treatments for mental health problems. The most common medicinal plants which have been used in Iran for the cure of stress and anxiety are Viper,s-buglosses, Dracocephalum, valerian, chamomile, common hop, Hawhorns, and Lavender. Medicinal plants and herbs can be used for treatment and alleviating negative effects of stress, anger and depression during the global pandemic.
Article
Withania somnifera (WS) extracts have been used in traditional medicine for millennia to promote healthy aging and wellbeing. WS is now also widely used in Western countries as a nutritional supplement to extend healthspan and increase resilience against age-related changes, including sleep deficits and depression. Although human trials have supported beneficial effects of WS, the study designs have varied widely. Plant material is intrinsically complex, and extracts vary widely with the origin of the plant material and the extraction method. Commercial supplements can contain various other ingredients, and the characteristics of the study population can also be varied. To perform maximally controlled experiments, we used plant extracts analyzed for their composition and stability. We then tested these extracts in an inbred Drosophila line to minimize effects of the genetic background in a controlled environment. We found that a water extract of WS (WSAq) was most potent in improving physical fitness, while an ethanol extract (WSE) improved sleep in aged flies. Both extracts provided resilience against stress-induced behavioral changes. WSE contained higher levels of withanolides, which have been proposed to be active ingredients, than WSAq. Therefore, withanolides may mediate the sleep improvement, whereas so-far-unknown ingredients enriched in WSAq likely mediate the effects on fitness and stress-related behavior.
Article
CGS 9895 is a pyrazoloquinoline closely related to the benzodiazepine agonist CGS 9896 and the benzodiazepine antagonist CGS 8216. In anxiolytic test procedures, this compound generalizes to CGS 9896 discriminative stimuli, produces an increase in punished responding, and partially antagonizes pentylenetetrazol discriminative stimuli. This anxiolytic activity is not, however, accompanied by any detectable sedation or muscle relaxation. CGS 9895 does not impair rotorod performance or reduce motor activity and does not potentiate ethanol-induced rotorod impairment or hexobarbital-induced sleeptime. This compound does not generalize to diazepam discriminative stimuli, suggesting a difference between the internal stimuli produced by this drug and those of diazepam. Only weak anticonvulsant activity is noted with CGS 9895. In addition to the benzodiazepine agonist effects of this compound, CGS 9895 is capable of antagonizing the rotorod deficit produced by diazepam. It also selectively antagonizes the sedative effect of diazepam in the conflict procedure without reducing the anxiolytic effect of diazepam. Overall, CGS 9895 exhibits a novel combination of benzodiazepine agonist and antagonist properties. This unique profile suggests that CGS 9895 may be a clinically useful, novel anxiolytic agent.
Article
The present study investigated the anticonvulsant profile of Withania somnifera (W.s) in a lithium-pilocarpine model of status epilepticus (SE) in rats. Acute treatment with the root extract of W.s prolonged the latency to forelimb clonus but failed to protect against mortality. Acute pretreatment with W.s root extract enhanced the antiepileptic effect of diazepam and clonazepam. Rats chronically administered W.s (100, 200 mg/kg, p.o. × 7 d), when subjected to lithium-pilocarpine challenge showed a reduced mortality rate. Electrophysiological data further support the behavioural findings, as the root extract brought about a parallel change in seizure activity as paroxysmal spike activity appeared only from the 60 min record. Moreover, the seizure activity seemed to subside by 4 h in comparison with the control. The protective effect of the root extract appears to involve GABAergic mediation. © 1998 John Wiley & Sons, Ltd.
Article
Two new acylsterylglucosides, sitoindoside VII and sitoindoside VIII, were isolated from the roots of Withania somnifera Dun., and were screened for putative anti-stress activity because the plant is widely regarded as the ‘Indian Ginseng’ by practitioners of the traditional Indian system of medicine. Since an acceptable paradigm of pharmacological tests for anti-stress screening has yet to be evolved, a battery of tests were employed to delineate the activity of the test compounds. The total MeOH-H2O (1:1) extractives of the roots of W. somnifera (SG-1) and equimolecular combination of sitoindosides VII, VIII and withaferin-A, a common withanolide, (SG-2), exhibited significant anti-stress activity in all the test parameters used. The two sitoindosides also produced per se anti-stress activity, which was potentiated by withaferin-A. A preliminary acute toxicity study indicated that the compounds have a low order of acute toxicity. The anti-stress activity of SG-1 and SG-2 is consonant with the therapeutic use of W. somnifera in the Ayurveda, the Indian system of medicine.
Article
Two new glycowithanolides, sitoindoside IX (1) and sitoindoside X (2), isolated from Withania somnifera Dun., were evaluated for their immunomodulatory and CNS effects (anti-stress, memory and learning) in laboratory animals, because the plant extract is used by practitioners of the Indian systems of medicine for similar purposes. The two compounds, in doses of 100–400 μg/mouse, produced statistically significant mobilization and activation of peritoneal macrophages, phagocytosis and increased activity of the lysosomal enzymes secreted by the activated macrophages. Both these compounds (50–200 mg/kg p.o.) also produced significant anti-stress activity in albino mice and rats and augmented learning acquisition and memory retention in both young and old rats. These findings are consistent with the use of W. somnifera, in Ayurveda, to attenuate cerebral function deficits in the geriatric population and to provide non-specific host defence.
Article
The active principles of Withania somnifera (WS, 20–50 mg/kg, p.o.), consisting of equimolar amounts of sitoindosides. VII–X and withaferin A, were investigated for putative nootropic activity in an experimentally validated Alzheimer's disease (AD) model. The syndrome was induced by ibotenic acid (IA) lesioning of the nucleus basalis magnocellularis (NBM) in rats. Cognitive deficits induced in NMB-lesioned rats were assessed by attenuation of a learned active avoidance task and a decrease in frontal cortical and hippocampal acetylcholine (ACh) concentrations, choline acetyltransferase (ChAT) activity and muscarinic cholinergic receptor (MCR) binding. IA-induced NBM lesioning in rats caused a marked cognitive deficit, as evidenced by severe reduction of the learned task, and was accompanied by a significant decrease in frontal cortex and hippocampal ACh levels, ChAT activity and MCR binding. WS (50 mg/kg) significantly reversed both IA-induced cognitive deficit and the reduction in cholinergic markers after 2 weeks of treatment. The findings validate the medharasayan (promoter of learning and memory) effect of W. somnifera, as has been reported in Ayurveda.
Article
Although some promising results have been achieved by acetylcholinesterase inhibitors, an effective therapeutic intervention in Alzheimer's disease still remains an important goal. Sitoindosides VII–X, and withaferin-A, isolated from aqueous methanol extract from the roots of cultivated varieties of Withania somnifera (known as Indian Ginseng), as well as Shilajit, a pale-brown to blackish brown exudation from steep rocks of the Himalaya mountain, are used in Indian medicine to attenuate cerebral functional deficits, including amnesia, in geriatric patients. The present investigation was conducted to assess whether the memory-enhancing effects of plant extracts from Withania somnifera and Shilajit are owing to neurochemical alterations of specific transmitter systems. Therefore, histochemistry to analyse acetylcholinesterase activity as well as receptor autoradiography to detect cholinergic, glutamatergic and GABAergic receptor subtypes were performed in brain slices from adult male Wistar rats, injected intraperitoneally daily with an equimolar mixture of sitoindosides VII–X and withaferin-A (prepared from Withania somnifera) or with Shilajit, at doses of 40 mg/kg of body weight for 7 days.
Article
A novel test for the selective identification of anxiolytic and anxiogenic drug effects in the rat is described, using an elevated + -maze consisting of two open arms and two enclosed arms. The use of this test for detecting such drug effects was validated behaviourally, physiologically, and pharmacologically. Rats made significantly fewer entries into the open arms than into the closed arms, and spent significantly less time in open arms. Confinement to the open arms was associated with the observation of significantly more anxiety-related behaviours, and of significantly greater plasma corticosterone concentrations, than confinement to the closed arms. Neither novelty nor illumination was a significant contributor to the behaviour of the rats on the + -maze. A significant increase in the percentage of time spent on the open arms and the number of entries into the open arms was observed only within clinically effective anxiolytics (chlordiazepoxide, diazepam and, less effectively, phenobarbitone). Compounds that cause anxiety in man significantly reduced the percentage of entries into, and time spent on, the open arms (yohimbine, pentylenetetrazole, caffeine, amphetamine). Neither antidepressants nor major tranquilisers had a specific effect. Exposure to a holeboard immediately before placement on the + -maze showed that behaviour on the maze was not clearly correlated either with exploratory head-dipping or spontaneous locomotor activity.
Article
Brain tribulin activity in rats with an inherited predisposition to audiogenic epilepsy was studied after seizures of different intensity were induced by an electric bell. Weak seizures (from 0 to 2 arbitrary units) did not produce any changes in endogenous inhibitory activity towards either monoamine oxidase (MAO) A or B. Moderate seizures were characterized by increases in both MAO A and MAO B inhibitory activity (up to 1.9-fold). Complete tonic epileptiform seizures with total areflexia (4 arbitrary units) induced further augmentation (up to 2.5-fold) of MAO A but not of MAO B inhibitory activity. This dissociation between the two inhibitory activities points to the existence of a separate MAO A-inhibiting component of brain tribulin which is different from isatin.
Article
Rats when forced to swim in a cylinder from which they cannot escape will, after an initial period of vigorous activity, adopt a characteristic immobile posture which can be readily identified. Immobility was reduced by various clinically effective antidepressant drugs at doses which otherwise decreased spontaneous motor activity in an open field. Antidepressants could thus be distinguished from psychostimulants which decreased immobility at doses which increased general activity. Anxiolytic compounds did not affect immobility whereas major tranquilisers enhanced it. Immobility was also reduced by electroconvulsive shock, REM sleep deprivation and "enrichment" of the environment. It was concluded that immobility reflects a state of lowered mood in the rat which is selectively sensitive to antidepressant treatments. Positive findings with atypical antidepressant drugs such as iprindole and mianserin suggest that the method may be capable of discovering new antidepressants hitherto undetectable with classical pharmacological tests.
Article
1 Pairs of male rats were placed in a test box for 10 min and the time they spent in active social interaction was scored. Maximum active interaction was found when the rats were tested under low light in a box with which they were familiar. When the light level was increased or when the box was unfamiliar active social interaction decreased. 2 Exploration (time spent sniffing objects) decreased in the same way in relation to test conditions as did social interaction. As these decreased, defecation, and freezing increased. 3 Anosmic controls showed that the decrease in social interaction across test conditions could not be attributed to olfactory changes in the partner. 4 Chlordiazepoxide (5 mg/kg) given chronically prevented or significantly reduced the decrease in social interaction that occurred in undrugged rats as the light level or the unfamiliarity of the test box was increased. Controls showed that this effect could not be entirely attributed to chlordiazepoxide acting selectively to increase low levels of responding. 5 The effect of chronic chlordiazepoxide contrasts with its action when given acutely; in the latter case it has only sedative effects. 6 Whether this test can be used as an animal model of anxiety is discussed and this test is compared with existing tests of anxiety.
Article
Animal behavioural models of psychiatric disorders cannot exactly simulate human psychopathology, but they can be used to evaluate the behavioural changes induced by drugs and to suggest hypotheses about the functions of the CNS and its involvement in psychiatric disorders. This should lead to a more heuristic classification of psychotropic drugs and to clarification of their therapeutic possibilities. The following animal models simulate aspects of depressive disorders and are sensitive to the antidepressant effects of drugs. (i) The forced swimming test: described as 'behavioural despair' on the assumption that the animal has given up hope of escaping. (ii) The 'restraint stress' test: this may indicate a failure to adapt to stress. (iii) The learned-helplessness model: exposed to uncontrollable events, animals exhibit learning performance deficit and behavioural changes, including decreased locomotor activity and loss of appetite. (iv) Waiting behaviour: improvement in the ability to wait for and/or postpone an active response; this could be related to the reported beneficial effects of antidepressants on impulsive behaviour.
Article
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.
Article
Unlabelled: 1. GABAergic mechanisms have been generally ignored in the study of mood disorders and antidepressant drug (AD) action. Recently data have accumulated indicating that GABAergic mechanisms may be involved in both of these. 2. Mood disorders: GABA levels are reported to be low in the CSF and plasma of depressed patients and are related to mood changes. GABAB receptors are decreased in the frontal cortex in two rodent behavioral models of depression and GABA release is reported diminished in the hippocampus. GABAergic drugs (progabide, fengabine) reverse the behavioral deficits in the rodent models and exert clear therapeutic effects in depressed patients. 3. AD action: In behavioral models imipramine upregulates GABAB receptors only in those animals which respond behaviorally to the AD. In naive rats repeated administration of varied ADs upregulates GABAB receptors in the frontal cortex whereas non-ADs (including amphetamine) do not. Bicuculline inhibits the action of imipramine in the learned helplessness model. GABAA receptor stimulation enhances noradrenaline release in the ventral NA pathway. 4. Conclusions: GABAergic mechanisms likely play a role in the modulation of mood and increasing GABAergic tone exerts and antidepressant effect. Actions at GABA synapses appear to be a fundamental facet of ADs, perhaps together with beta-adrenoceptor mediated events.
Article
We have examined the anxiolytic activity of acute and chronic antidepressant treatment in an animal model of anxiety involving novelty-suppressed feeding. Rats were food deprived for 48 h, placed into a novel environment containing food, and the latency to begin eating was recorded. Chronic (21 days), but not acute injections of desipramine (DMI; 10 mg/kg) and amitriptyline (AMI; 10 mg/kg) significantly reduced the latency to begin eating compared to controls, but the percentage decrease was not as great as that seen with either acute or chronic treatment with diazepam (2 mg/kg) or adinazolam (20 mg/kg). A time course study indicated that at least 2 weeks of treatment was necessary to observe a significant anxiolytic effect of antidepressants. The anxiolytic effect of the antidepressants was specific to the novel environment, as 2 weeks of treatment with either diazepam or DMI did not influence the latency to begin eating in the home cage. Finally, a single dose of the central benzodiazepine receptor antagonist, Ro15-1788 (20 mg/kg), given 15 min prior to testing, did not block the anxiolytic effects of chronic DMI, while it completely eliminated the effect of chronic diazepam treatment. These data suggest that antidepressants acquire anxiolytic properties following chronic administration and that this effect appears to be independent of the benzodiazepine receptor system.
Article
Anxiogenic agents, yohimbine, pentylenetetrazole (PTZ), quinine, bufotenine, flumazenil and isatin were administered (ip) to rats at doses known to induce anxiety in this species. All the drugs exhibited anxiogenic response on the elevated plus-maze and induced a parallel increase in endogenous brain monoamine oxidase (MAO) inhibitory (tribulin) activity. The intensity of the drug-induced anxiety was fairly well correlated with the magnitude of increase in the MAO A inhibitory component of tribulin but not so with its MAO B inhibitory component. Thus, in the doses used, the degree of anxiogenic activity was PTZ > yohimbine > bufotenine > quinine > isatin > flumazenil, in terms of % entries on the open arms of the maze, whereas the magnitude of endogenous MAO A inhibition was PTZ > yohimbine > bufotenine > quinine > flumazenil > isatin. The results indicate that the MAO A inhibitory component of tribulin, rather than its MAO B inhibitory component, may be responsible for the postulated function of tribulin as an endogenous marker of anxiety.
Article
Rodent models of clinical anxiety are extensively used for evaluating putative anxiolytic activity. In the present review, the available methods which can be utilized by most laboratories, have been discussed. These methods have been categorized as methods involving conditioning techniques and those not involving conditioning. In most cases, the methodology has been briefly discussed in terms of experimental use and efficacy of benzodiazepine and the newer non-benzodiazepine anxiolytics.
Article
Plants from all over the world such as Eleutherococcus senticosus, Panax ginseng, Raponticum carthamoides, Rhodiola rosea, Withania somnifera and Ocimum sanctum have been extensively evaluated for their adaptogenic potential. However, none of them has been successfully introduced as an adaptogen in the clinic. This paper discusses some of the problems in evaluation of adaptogens which have precluded their inclusion as clinically useful drugs. We further discuss our results with six rasayana plants from Ayurveda, which were studied for their adaptogenic potential.
Article
Rodent models of clinical depression are extensively used for the evaluation of putative antidepressants. In the present review, the available experimental methods which can be utilized by most laboratories involved in preclinical screening of antidepressants, have been discussed. The methods have been categorized on the basis of induction of the depressive state or on the assumption that monoamine deficiency leads to depression. These methods have been critically validated in terms of efficacy of standard antidepressants in these tests and, in some cases, by the neurochemical basis of depression, namely, the deficient monoaminergic theory of clinical depression.
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  • W T Mckinney
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Lloyd, K. G., Zivkovic, B., Scatton, B., Morselli, P. L., Barth oloni, G.: The GABAergic hypoth esis of depr ession. Prog. Ne uropsychopharmacol. Bioi. Psychiat. 13: 341-351, 1989. McKinney, W. T.: Behaviou ral models of depression in mon-keys. In: Animal models in psychiatry and neurology (Ha nin, E., Usdin, E., eds.). Pergamon Press, Ox ford, 1979, pp. 117-1 26.
Phar-macological effects of Witha nia somnifera root extract on GABA recept or complex GABAergic dru gs as putative an-tidepressants: a review of available data
  • A K Mehta
  • P Binkley
  • S S Gandhi
  • M K Ticku
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Tel: (05 42) 31 1099; Fax: (05 42) 31 6483; e-mail: salil@banaras.ernet
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