We value your privacy
Withania somnifera (Ashawagandha) is very revered herb of the Indian Ayurvedic system of medicine as a Rasayana (tonic). It is used for various kinds of disease processes and specially as a nervine tonic. Considering these facts many scientific studies were carried out and its adaptogenic / anti-stress activities were studied in detail. In experimental models it increases the stamina of rats during swimming endurance test and prevented adrenal gland changes of ascorbic acid and cortisol content produce by swimming stress. Pretreatment with Withania somnifera (WS) showed significance protection against stress induced gastric ulcers. WS have anti-tumor effect on Chinese Hamster Ovary (CHO) cell carcinoma. It was also found effective against urethane induced lung-adenoma in mice. In some cases of uterine fibroids, dermatosarcoma, long term treatment with WS controlled the condition. It has a Cognition Promoting Effect and was useful in children with memory deficit and in old age people loss of memory. It was also found useful in neurodegenerative diseases such as Parkinson's, Huntington's and Alzeimer's diseases. It has GABA mimetic effect and was shown to promote formation of dendrites. It has anxiolytic effect and improves energy levels and mitochondrial health. It is an anti-inflammatory and anti-arthritic agent and was found useful in clinical cases of Rheumatoid and Osteoarthritis. Large scale studies are needed to prove its clinical efficacy in stress related disorders, neuronal disorders and cancers.
Do you want to read the rest of this article?
... Ashwagandha improves the body's defense against disease by improving the cell-mediated immunity. It also possesses potent antioxidant properties that help protect against cellular damage caused by free radicals . Ashwagandha is taken for treating cold and coughs, ulcers, emaciation, diabetes, conjunctivitis, epilepsy, insomnia, senile dementia, leprosy, Parkinson's disease, nervous disorders, rheumatism, arthriti s, intestinal infections, bronchitis, asthma, impotence . ...
... Ashwagandha is taken for treating cold and coughs, ulcers, emaciation, diabetes, conjunctivitis, epilepsy, insomnia, senile dementia, leprosy, Parkinson's disease, nervous disorders, rheumatism, arthriti s, intestinal infections, bronchitis, asthma, impotence . It is being widely used in ayurvedic system, as a Rasayana (it is an herbal preparation that promotes physical and mental health) . Therefore there is a lot of scope to improve the productivity of ashwagandha through genetic selection and crop improvement. ...
... Congenital adrenal hyperplasia (CAH), like PCOS, is characterized by insulin resistance . The Ayurvedic herb, Ashwagandha, (Withania somnifera), also known as Indian ginseng, has been used for millennia with numerous beneficial health effects having been reported; it helps fight infections, deters oil plugs from being formed on the skin, and is a natural and healthy way to treat acne scars [6,7]. A newer usage of Ashwagandha root is as an insulin sensitizer . ...
... Ashwagandha root, often referred to as Indian ginseng, was first recorded for medical use by the Ayurveda [6,7]. Today, it is widely grown in tropical and subtropical areas. ...
An elderly woman presented with acne and male pattern alopecia, which upon diagnostic evaluation was found to be due to nonclassic 11-hydroxylase deficiency. We previously reported that Ashwagandha root ameliorates nonclassic 3- β -ol dehydrogenase and aldosterone synthase deficiencies. This is the first report of its use being associated with amelioration of nonclassic 11-hydroxylase deficiency, where its apparent effects appear to be dose-related.
... Withania somnifera (WS), also known as ashwagandha, is a potent anti-osteoarthritic and anti-inflammatory plant used in Ayurveda . ...
Chronic joint inflammatory disorders such as osteoarthritis and rheumatoid arthritis have in common an upsurge of inflammation, and oxidative stress, resulting in progressive histological alterations and disabling symptoms. Currently used conventional medication (ranging from pain-killers to biological agents) is potent, but frequently associated with serious, even life-threatening side effects. Used for millennia in traditional herbalism, medicinal plants are a promising alternative, with lower rate of adverse events and efficiency frequently comparable with that of conventional drugs. Nevertheless, their mechanism of action is in many cases elusive and/or uncertain. Even though many of them have been proven effective in studies done in vitro or on animal models, there is a scarcity of human clinical evidence. The purpose of this review is to summarize the available scientific information on the following joint-friendly medicinal plants, which have been tested in human studies: Arnica montana, Boswellia spp., Curcuma spp., Equisetum arvense, Harpagophytum procumbens, Salix spp., Sesamum indicum, Symphytum officinalis, Zingiber officinalis, Panax notoginseng, and Whitania somnifera.
... The analgesic activity is also due to its action of soothing the nervous system from pain responses . Also it is suggested that serotonin may be involved in the analgesic effects of W. somnifera . An experimental study has demonstrated the chondroprotective activity of W. somnifera in human cartilage tissue . ...
... Ashwagandha (Withania somnifera) is one of the plants being described in Ayurveda as a potent anti-inflammatory plant (178). It is rich in Withaferin A, a steroidal phytochemical which can prevent proceeding of NF-κβ signaling pathway (179). ...
Self-help by means of dietary interventions can help in management of various disorders including rheumatoid arthritis (RA), a debilitating autoimmune disease. Dietary interventions necessitate a widespread appeal for both patients as well as clinicians due to factors including affordability, accessibility, and presence of scientific evidences that demonstrate substantial benefits in reducing disease symptoms such as pain, joint stiffness, swelling, tenderness and associated disability with disease progression. However, there is still an uncertainty among the community about the therapeutic benefits of dietary manipulations for RA. In the present review, we provide an account of different diets and their possible molecular mechanism of actions inducing observed therapeutic benefits for remission and management of RA. We further indicate food that can be a potential aggravating factor for the disease or may help in symptomatic relief. We thereafter summarize and thereby discuss various diets and food which help in reducing levels of inflammatory cytokines in RA patients that may play an effective role in management of RA following proper patient awareness. We thus would like to promote diet management as a tool that can both supplement and complement present treatment strategies for a better patient health and recovery.
... Another study suggested that Withaferin A, a withanolide obtained from W. somnifera, could inhibit H. pylori-induced production of IL-1β in dendritic cells and could be utilized as a novel preventive and remedial agent in cases of gastric cancer. [115,117] Zingiber officinale Zingiber officinale Roscoe or ginger (Family: Zingiberacae) is a widespread medicinal plant and a common condiment used in food and drink. It is used for a broad collection of unrelated disorders such as arthritis, muscular aches, rheumatism, pain, sprains, sore throat, constipation, cramp, stomach upset, indigestion, nausea, diarrhea, vomiting, dementia, hypertension, infectious diseases, fever, and helminthiasis. ...
Herbal medicines are now commonly used all over the world and this has increased global demand. Quality, safety, and efficacy of these drugs have become a serious concern. This review presents the medicinal plants cited in folklore that are used to treat gastrointestinal ulcers. Electronic databases, that is, Web of Science, PubMed, Scopus, and Google Scholar were searched to identify the gastroprotective effects of each plant. Ethnopharmacological studies have reported various botanical products with antiulcer activities, but there has been limited scientific research, presenting clinical data to validate the efficacy and safety of medicinal herbs as gastroprotective agents. Most studies centered on pharmacological properties of medicinal herbs as used animals models. This information has prompted us to compile a list of the medicinal herbs cited in folklore with gastroprotective activity.
... Withania somnifera  belongs to the Solanaceae family and is commonly known as "Indian Ginseng" or "Indian Winter cherry" 34 . It wildly grows in all drier parts of Asia, Africa, Congo, South Africa, Egypt, Morocco, Jordan, Bangladesh, Sri-Lanka, Nepal, Pakistan and parts of subtropical India such as Madhya Pradesh, Uttar Pradesh, Punjab and northwest. ...
The process of licking and gulping it is called as Lehana. The substance subjected for Lehana is called Lehya, this concept is also adopted in drug delivery for neonates and infants where the proposed drug is mixed with any of honey, sugar, ghee, etc made into lickables and fed to child. The purpose and object of Lehana karma look to prevent the diseases by establishing due immunity and to promote the physical and psychic strength providing nutrition. The broad spectrum actions of Kumarabharana Prasha may be attributed to its constituent's namely Bhasmas (calx) of Swarna (Gold), Rajata (Silver), Pravala (coral)and Choorna of Yastimadhu (Glycyrrhiza glabra Linn.), Amalaki (Emblica officinalis Gaertn.), Ashwagandha (Withania somnifera (L.) Dunal), Shunti (Zingiber officinale Roscoe), Pippali (Piper longum Linn.), Harithaki (Terminalia chebula Retz.), Vacha (Acorus calamus Linn.) and all these drugs given one Bhavana with Swarasa (extract juice) of Guduchi (Tinospora cordifolia Willd.), Brahmi (Bacopa monnieri Linn.) and Tulsi (Ocimum tenuiflorum Linn.), with honey and ghee. This can be readily administered to child in requisite dose. This article highlights the ingredients, method of preparation, and probable mechanism of action of Kumarabharana Prasha.
... Historically, the plant has been used therapeutically for boosting the brain function including memory retrieval. Thus has a cognition promoting effect in adults and children (Singh et al. 2011). It consists of two components: withanolides, withanamides. ...
Glycogen synthase kinase 3 β (GSK-3 Beta) is a potential target for developing an effective therapeutic effect in Alzheimer's disease (AD). Currently, no such drug or molecules has been found till date which can cure AD completely. Few drugs such as acetylcholinesterase inhibitors and memantine are ineffective in the later stages of the disease. Therefore, with the advancements in computational biology approaches, it is possible to combat alzheimer’s disease by targeting one of the kinases i.e. GSK-3 β involved in hyper phosphorylation of tau (a reliable marker of neurodegenerative disorders). In this study, we have carried out alzheimer’s structure-based drug designing with GSK-3 β. By applying appropriate docking methodology, we have identified few plant-derived compounds which show enhanced target selectivity than the conventional alzheimer's drug (such as memantine). Here we enumerate the comparison among the current and future AD therapy on the basis of their binding affinities. As a result, a large library of compounds has been screened as potent drug targets. It was also observed that withanolide–A (extracted from roots of withania somnifera) has the potential to emerge as the eventual drug for the AD. Moreover, few other phytocompounds such as celastrol, kenpaullone, quercetin, alsterpaullone have also shown enhanced activity in the decreasing order of their binding affinities.
... 3e13 In India many plants and plant products are vended in markets that claim for ability to treat paralysis, some of which are Punarnava powder (containing Hogweed or Boerhavia diffusa), Ashwagandha powder (containing Withania somnifera). 14,15 The poly herbal drug Majoon-e-Azaraqi is an ancient herbal Unani compound formulation which is therapeutically use in nerve strengthening, hemiplegia, facial paralysis, tremor, trembling, rheumatism, epilepsy and neurasthenia. Majoon-e-Azaraqi is constituted of 15 ingredients (Strychnos nuxvomica, Borago officinalis, Lavandula stoechas, Cochlospermum religiosum, Cocos nucifera, Pinus gerardiana, Eletarria cardamomum, Curcuma zeodaria, Pastinaca secacul, Santalum album, Emblica officinalis, Terminalia chebula, Aquilaria agallocha, Syzygium aromaticum and Sugar). ...
Paralysis is the loss of the ability of one or more muscles to move, due to disruption of signaling between the nervous system and muscles. The most common causes of paralysis are stroke, head injury, spinal cord injury (SCI) and multiple sclerosis. The search for cure of paralysis is yet to be found. Many ethnobotanical surveys have reported the use of medicinal plants by various ethnic communities in treating and curing paralysis. The present review discusses the use of medicinal plants in India for ameliorating and curing paralytic conditions, as well as discuses some of the important developments in future possible applications of medicinal plants in treatment of paralysis. This review reports the use of 37 medicinal plants for their application and cure of ailments related to paralysis. Out of the 37 plants documented, 11 plants have been reported for their ability to cure paralysis. However, the information on the documented plants were mostly found to be inadequate, requiring proper authentication with respect to their specificity, dosage, contradictions etc. It is found that despite the claims presented in many ethnobotanical surveys, the laboratory analysis of these plants remain untouched. It is believed that with deeper intervention on analysis of bioactive compounds present in these plants used by ethic traditional healers for paralysis, many potential therapeutic compounds can be isolated for this particular ailment in the near future.
... 24 Aswagandha is a known rasayana (rejuvenator) with growth promoting activity.  A rasayana is one that does therapeutic nutrition, immune enhancement and increases longevity.  Rasayana remedies are molecular nutrients and nutrition enhancing agents which acts through three mechanisms: rasa enhancing or direct nutrient effect, agni enhancing or promoter of digestion and metabolism and srotas purifying agents or promoters of microcirculation and tissue perfusion. ...
... This indicates clinical use of Withania somnifera in the prevention & treatment of many stress induced diseases like arteriosclerosis, premature ageing, arthritis, diabetes, hypertension & malignancy.  Two new glycowithanolides, sitoindoside IX (1) & sitoindoside X (2), isolated from Withania somnifera Dunal, were evaluated for their immunomodulatory & CNS effects like antistress, memory & learning in laboratory animals, because the plant extract was used by practitioners of the Indian system of medicine for similar purpose. Both these compounds (50-200mg/kg) produced significant anti stress activity in albino mice & rats, augmented learning acquisition & memory retention in both young & old rats. ...
... 24 Aswagandha is a known rasayana (rejuvenator) with growth promoting activity.  A rasayana is one that does therapeutic nutrition, immune enhancement and increases longevity.  Rasayana remedies are molecular nutrients and nutrition enhancing agents which acts through three mechanisms: rasa enhancing or direct nutrient effect, agni enhancing or promoter of digestion and metabolism and srotas purifying agents or promoters of microcirculation and tissue perfusion. ...
Objectives: To evaluate the effectiveness of Aswagandha Ghrita Matra Basti on Karshya (underweight) in children. Materials and methods: The study was carried out at inpatient level in a tertiary Ayurveda hospital attached to teaching institute. 30 children satisfying diagnostic criteria and age 6-10 years were included and distributed into two groups of 15 patients each. Group A were given Abhyanga with Tila Taila and Nadisweda followed by Matra Basti with Ashwagandha Ghrita (dose as per age) along with dietary advice for 15 days. In Group B, patients were given only dietary advice for 15 days. The patients of both the groups were followed up after a period of 30 days i.e., on the 45 th day. Results and Discussion: It was found that Matra Basti with Ashwagandha Ghrita showed highly significant results in subjective as well as objective parameters such as general weakness, state of hunger, activity or interest, weight in Kg, height in cm, chest circumference, mid arm circumference and B.M.I. Conclusion: Aswagandha Ghrita Matra Basti is effective in improving all the anthropometrical measurements and in reducing the associated complaints of Karshya and hence useful in the management of Karshya in children.
... Withania somnifera (WS) Dunal (family Solanaceae), also known as Ashwagandha or Indian Ginseng, is a plant widely used in traditional Ayurvedic medicine in India since antiquity . It is included in the Indian Pharmacopoeia (Singh et al., 2011) as a safe o cial medication for the treatment of several ailments (Dar et al., 2016) and recent evidence supports its anti-inflammatory, immunomodulatory, neuroprotective (Bhatnagar et al., 1975;Dar et al., 2016;Yenisetti et al., 2016) and free-radical scavenging (Bhattacharya et al., 2001;Davis and Kuttan, 2001;Prakash et al., 2014;Dar et al., 2015) properties. Moreover, WS has been shown to modulate GABAergic [(g-amino-butyric acid (GABA)] (Mehta et al., 1991; and cholinergic (Schliebs et al., 1997) neurotransmission and to a ect di erent properties of addictive drugs. ...
Morphine- and ethanol-induced stimulation of neuronal firing of ventral tegmental area (VTA) dopaminergic neurons and of dopamine (DA) transmission in the shell of the nucleus accumbens (AcbSh) represents a crucial electrophysiological and neurochemical response underlying the ability of these compounds to elicit motivated behaviors and trigger a cascade of plasticity-related biochemical events. Previous studies indicate that the standardized methanolic extract of Withania somnifera roots (WSE) prevents morphine- and ethanol-elicited conditioned place preference and oral ethanol self-administration. Aim of the present research was to investigate whether WSE may also interfere with the ability of morphine and ethanol to stimulate VTA dopaminergic neurons and thus AcbSh DA transmission as assessed in male Sprague-Dawley rats by means of patch-clamp recordings in mesencephalic slices and in vivo brain microdialysis, respectively. Morphine and ethanol significantly stimulated spontaneous firing rate of VTA neurons and DA transmission in the AcbSh. WSE, at concentrations (200–400 μg/ml) that significantly reduce spontaneous neuronal firing of VTA DA neurons via a GABAA- but not GABAB-mediated mechanism, suppressed the stimulatory actions of both morphine and ethanol. Moreover, in vivo administration of WSE at a dose (75 mg/kg) that fails to affect basal DA transmission, significantly prevented both morphine- and ethanol-elicited increases of DA in the AcbSh. Overall, these results highlight the ability of WSE to interfere with morphine- and ethanol-mediated central effects and suggest a mechanistic interpretation of the efficacy of this extract to prevent the motivational properties of these compounds.
... WS has been described thoroughly in classical texts of Ayurveda such as Charaka Samhita, Sushruta Samhita and Bhavprakash Nighantu for boosting homeostasis, tissue nourishment, improvement of stress tolerance, arresting degeneration, and as a vitality promoter (Gogte, 2000) (Vaidya, 2000). Similar effects of WS in several indications like sarcopenia, arthritis, asthma, neurodegeneration, cognitive dysfunction, stress and in immunocompromised patients are observed in clinical practice of Ayurveda (Singh et al., 2011). The classical texts of Ayurveda recommend predominantly roots and leaves of WS for their several properties including anti-inflammatory, prokinetic, aphrodisiac, muscle-strengthening, muscle-relaxant, anti-insomnia, anxiolytic, antistress, analgesic, anthelmintic and anti-anginal (AyuSoft drug database).WS is a well known botanical used as a folklore remedy for improving strength and vitality. ...
Withania somnifera (L.) Dunal (WS) is one of the most-studied Rasayana botanicals used in Ayurveda practice for its immunomodulatory, anti-aging, adaptogenic, and rejuvenating effects. The botanical is being used for various clinical indications, including cancer. Several studies exploring molecular mechanisms of WS suggest its possible role in improving clinical outcomes in cancer management. Therefore, research on WS may offer new insights in rational development of therapeutic adjuvants for cancer.
Aim of this review
The review aims at providing a detailed analysis of in silico, in vitro, in vivo and clinical studies related to WS and cancer. It suggests possible role of WS in regulating molecular mechanisms associated with carcinogenesis. The review discusses potential of WS in cancer management in terms of cancer prevention, anti-cancer activity, and enhancing efficacy of cancer therapeutics.
Material and methods
The present narrative review offers a critical analysis of published literature on WS studies in cancer. The reported studies were analysed in the context of pathophysiology of cancer, commonly referred as ‘cancer hallmarks’. The review attempts to bridge Ayurveda knowledge with biological insights into molecular mechanisms of cancer.
The critical analysis suggests an anti-cancer potential of WS with a key role in cancer prevention. The possible mechanisms for these effects are associated with the modulation of apoptotic, proliferative, and metastatic markers in cancer. WS can attenuate inflammatory responses and enzymes involved in invasion and metastatic progression of cancer.
The properties of WS are likely to be mediated through withanolides, which may activate tumor suppressor proteins to restrict proliferation of cancer cells, regulate the genomic instability, and energy metabolism of cancer cells. The reported studies indicate the need for deeper understanding of molecular mechanisms of WS in inhibiting angiogenesis and promoting immunosurveillance. Additionally, WS can augment efficacy and safety of cancer therapeutics.
The experimentally-supported evidence of immunomodulatory, anti-cancer, adaptogenic, and regenerative attributes of WS suggest its therapeutic adjuvant potential in cancer management. The adjuvant properties of withanolides can modulate multidrug resistance and reverse chemotherapy-induced myelosuppression. These mechanisms need to be further explored in systematically designed translational and clinical studies that will pave the way for integration of WS as a therapeutic adjuvant in cancer management.
... Traditionally, it is used as medicine for more than 3000 years against various ailments, and it is an essential constituent of over 200 traditional medicinal formulations . Some of the important therapeutic properties of W. somnifera are immunoregulatory, anticancer, anti-arthritic and recovery from neurodegenerative disorders . The higher market demand for W. somnifera has caused a tremendous burden on its natural reservoirs during the last decades. ...
Withania somnifera L. is an endangered medicinal plant of higher market value. The in vitro callus cultures were established on Murashige and Skoog (MS) media augmented with different plant growth regulators. The MS medium containing 0.5 mg∙L-1 of each TDZ and NAA was found to be optimal for callus formation and growth. Further, callus cultures were raised in different light wavelengths to find the right wavelength carrying the photons for the ideal cell growth of W. somnifera. Among the different wavelengths, red light was best for maximum biomass accumulation in callus culture. However, violet light condition was proven to be favouring the phenols and flavonoids synthesis in the callus cultures. Compared to other wavelengths, red light grown callus extract showed significantly higher content of chlorogenic acid, and withaferin A. This study concludes that red light treatment was optimum for maximum biomass accumulation and anti-oxidant activity in calli of W. somnifera.
... Such adaptogens are efficacious in eradicating fatigue and its molecular mechanism has been explored as well . Pharmacological studies have confirmed that Ashwagandha is a multipurpose herb and has anti-inflammatory, neuroprotective, adaptogenic, memory-enhancing, hematopoietic, sleep-inducing and anxiolytic properties 8,14]. A study conducted on mice using the aqueous suspensions of the powdered Ashwagandha root exhibited anti-stress activity . ...
Background Stress, anxiety and impeded sleep are a frequent feature of life in modern societies. Across socio-economic strata, stress, anxiety and ineffective sleep detract from healthful living and serve as precursors of various ailments. The use of herbs to offset these antecedents and outcomes has greatly increased in recent years. Ashwagandha, an adaptogenic Ayurvedic herb, has been often used to combat and reduce stress and thereby enhance general wellbeing. While there have been other studies documenting the use of Ashwagandha for stress resistance, this is the first study to use a high-concentration root extract while also varying the dosage substantially. Therefore, this is the first study to offer insight into dose-response of a high concentration root extract. Material and methods In this eight-week, prospective, randomized, double-blind, placebo-controlled study, the stress-relieving effect of Ashwagandha root extract was investigated in stressed healthy adults. Sixty male and female participants with a baseline perceived stress scale (PSS) score >20 were randomized to receive capsules of Ashwagandha extract 125 mg, Ashwagandha extract 300 mg or identical placebo twice daily for eight weeks in a 1:1:1 ratio. Stress was assessed using PSS at baseline, four weeks and eight weeks. Anxiety was assessed using the Hamilton-Anxiety (HAM-A) scale and serum cortisol was measured at baseline and at eight weeks. Sleep quality was assessed using a seven-point sleep scale. A repeat measures ANOVA (general linear model) was used for assessment of treatment effect at different time periods. Post-hoc Dunnett's test was used for comparison of two treatments with placebo. Results Two participants (one each in 250 mg/day Ashwagandha and placebo) were lost to follow-up and 58 participants completed the study. A significant reduction in PSS scores was observed with Ashwagandha 250 mg/day (P < 0.05) and 600 mg/day (P < 0.001). Serum cortisol levels reduced with both Ashwagandha 250 mg/day (P < 0.05) and Ashwagandha 600 mg/day (P < 0.0001). Compared to the placebo group participants, the participants receiving Ashwagandha had significant improvement in sleep quality. Conclusion Ashwagandha root aqueous extract was beneficial in reducing stress and anxiety.
... Over centuries, this herb has been used as a "Rasayana" or rejuvenator and aided in promoting health and longevity, slowing the aging process, and acted as a revitalizer. Ashwagandha is also known as "Sattvic Kapha Rasayana" for its tremendous impact on growth, body weight, lubricating factor, and major tissue development activities . Many pharmacological studies have been conducted to investigate the multiple medicinal properties of Ashwagandha . ...
Background Ashwagandha is an excellent adaptogen that is being used since ancient times in Ayurvedic medicine. Traditionally, it is used for various ailments and general well-being, including the treatment of geriatric patients. Managing quality of life (QoL) remains a challenge for the elderly population, especially joint pain management, sleep, and general well-being. With a growing global elderly population, QoL management with efficient medication and supplementation is the major healthcare requirement. Objective The objective of this study was to assess the safety, efficacy, and tolerability of Ashwagandha (Withania somnifera (L.) Dunal.) root extract on the improvement of general health and sleep in elderly people. Methods This 12-week, prospective, randomized, double-blind, placebo-controlled study was conducted on individuals of either gender aged between 65-80 years. Participants were randomized to receive Ashwagandha root extract at a dose of 600 mg/day (n = 25) orally, or identical placebo capsules with the same dose (n = 25) for 12 weeks. Efficacy was assessed using the WHOQOL-BREF questionnaire, sleep quality, mental alertness on rising, and Physician's Global Assessment of Efficacy to Therapy (PGAET). The safety and tolerability were assessed using the clinical adverse events reporting and Patient's Global Assessment of Tolerability to Therapy (PGATT). Results Statistically significant (P<0.0001) improvement was observed in the Ashwagandha treatment group compared to the placebo. The mean (SD) total score of WHOQOL-BREF improved from 140.53 (8.25) at the baseline to 161.84(9.32) at the end of the study. The individual domain scores were also improved. At baseline, the sleep quality and the mental alertness on rising were comparatively low in both the groups. However, upon intervention, a significant increase in the quality of sleep (P<0.0001) and mental alertness (P<0.034) was observed in the Ashwagandha treatment group when compared to the placebo group. Overall improvement was observed for the general wellbeing, sleep quality, and mental alertness in the study population. The experimental group population displayed good tolerability to the test product and it was reported as safe and beneficial by the study participants. Conclusion The study outcomes suggest that Ashwagandha root extract was efficient in improving the QoL, sleep quality, and mental alertness as self-assessed by the elderly participants. The recommended dose used in this study could be effective for the elderly population.
Withania somnifera, commonly known as Ashwagandha, is one of the important herbs being used in Ayurveda since times immemorial. It has been classified as a ‘rasayana’ herb owing to its adaptogenic and rejuvenating properties. Both root and leaf extracts of the plant have been used for the treatment of various disorders such as cancer, anxiety, inflammation and various neurological disorders due to its wide array of properties. This chapter focuses on the effects of W. somnifera in various CNS disorders. Various pre-clinical studies investigating the use of W. somnifera in modulation of neuroplasticity, anxiety, neuroinflammation and neuroprotection have been discussed in detail. A plethora of studies confirm the use of W. somnifera and its active phytochemicals (Withaferin-A, Withanone, Withanoside IV, Withanolide A, sitoindosides VII-X) alone or in combination as potential therapeutic agents. W. somnifera can be incorporated as an important dietary supplement for management of anxiety and associated cognitive and functional impairments.
The root of Withania somnifera, commonly known as ashwagandha, is a traditional herb in the Indian Ayurvedic system of medicine and is used as a tonic. Here, we investigated whether W. somnifera root extract exhibits analgesic effects in plantar incision (PI) and spared nerve injury (SNI) rat models. Mechanical withdrawal threshold (MWT) was measured by von Frey filaments, and pain-related behavior was determined after operation by ultrasonic vocalization (USV) measurements. Indeed, we examined interferon-γ (IFN-γ) and interleukin-10 (IL-10) levels in the isolated dorsal root ganglia (DRG) following SNI in rats using an ELISA cytokine assay. MWT significantly increased 6 and 24 h after PI in rats receiving W. somnifera root extracts (100 and 300 mg/kg). Furthermore, the number of 22–27-kHz USV, which are a distress response, was significantly reduced at 6 and 24 h after PI in W. somnifera-treated rats (100 and 300 mg/kg). SNI-induced hyperalgesia and cytokine levels were significantly alleviated after treating with W. somnifera root extracts (100 and 300 mg/kg) for 15 continuous days. The main active compound, withaferin A, from the W. somnifera root extract has shown the CC chemokine family Receptor 2 (CCR2) antagonistic effects on monocyte chemoattractant protein-1 (MCP-1)-induced Ca²⁺ response in CCR2 stable cell line. These results indicate that W. somnifera root extract has a potential analgesic effect in rat models for both postoperative and neuropathic pain and shows potential as a drug or supplement for the treatment of pain.
Ayurveda claims to be effective in the treatment of psychosomatic disorders by means of lifestyle and nutritional counseling.
In a randomized controlled study mothers with burnout were randomized into two groups: Ayurvedic nutritional counseling (according to tradition), and conventional nutritional counseling (following the recommendations of a family doctor). Patients received five counseling sessions over twelve weeks.
Main outcome measures
Outcomes included levels of burnout, quality of life, sleep, stress, depression/anxiety, and spirituality at three and six months. It also included a qualitative evaluation of the communication processes.
We randomized thirty four patients; twenty three participants were included in the per protocol analysis. No significant differences were observed between the groups. However, significant and clinically relevant intra-group mean changes for the primary outcome burnout, and secondary outcomes sleep, stress, depression and mental health were only found in the Ayurveda group. The qualitative part of the study identified different conversational styles and counseling techniques between the two study groups. In conventional consultations questions tended to be category bound, while counseling-advice was predominantly admonitory. The Ayurvedic practitioner used open-ended interrogative forms, devices for displaying understanding, and positive re-evaluation more frequently, leading to an overall less asymmetrical interaction.
We found positive effects for both groups, which however were more pronounced in the Ayurvedic group. The conversational and counseling techniques in the Ayurvedic group offered more opportunities for problem description by patients as well as patient-centered practice and resource-oriented recommendations by the physician.
Trial Registration: NCT01797887.
Balarishtam is an Ayurvedic formulation used for the treatment of diseases caused due to Vata imbalance such as brain related
dysfunctions. The present study deals with the antioxidant activities such as DPPH assay, FRAP assay and Hydrogen Peroxide
Scavenging Activities of Balarishtam. The results indicated that Balarishtam has very good antioxidant properties which could be one
of the mechanisms responsible for the treatment of such diseases.
Keywords: Balarishtam, DPPH, FRAP, Hydrogen Peroxide Scavenging, Antioxidant.
The present study aimed to investigate the efficacy of the herb ashwagandha in the prevention of stressinduced
alterations in the ovary. Exposure of rats to two stressors i.e. restraint (1 h), then after a gap of 4
h to forced swimming exercise (15 minutes) every day for 4 weeks resulted in a significant increase in the
adrenocortical activity, indicating the activation of hypothalamo-pituitary-adrenal axis. Concomitantly,
there was a decrease in the weight, activities of 3β-hydroxysteroid dehydrogenase and antioxidant
enzymes, number of healthy antral follicles, corpora lutea and percentage of healthy granulosa cells of
the ovary, whereas the number of atretic follicles, the percentage of apoptotic granulosa cells and
malondialdehyde concentration of the ovary showed an increase in the stressed rats compared to those
of controls. However, stressed rats pre-treated with the alcoholic extract of ashwagandha (10mg/ kg body
weight, oral) did not show these adrenal and ovarian stress responses and did resemble controls. The
results for the first time reveal that an extract of ashwagandha is potent enough to inhibit activation of
hypothalamo-pituitary-adrenal axis and maintain normal gametogenic and antioxidant activities of the
ovary under stressful conditions.
The demand for the chemopreventive drug from the plant source is increasing in recent times, owing to its various biological activities without any adverse effect. The intention of this current study was to examine the anti-glioma effect of Withaferin A (WFA) on C6 glioma cell line model.
Materials and Methods
C6 glioma cells were administrated with different concentration of WFA (50, 100, 200 and 500 μg/mL) and DMSO (control) group to examine its anti-proliferative, anti-inflammatory and pro-apoptotic activities.
Treatment with WFA showed a significant decline in the glioma cell count in a dose-dependent manner and thus proving its anti-proliferative effect. Similarly, inflammatory markers were also substantially lowered upon treatment with different concentration of WFA. However, DNA fragmentation and apoptotic markers like Caspase-3 and 9 were concomitantly enhanced after co-cultured with different concentration of WFA and thus exhibiting its cytotoxicity efficacy. Furthermore, the protein expression of Bcl2 and Bax were markedly downregulated and upregulated respectively; upon treatment with WFA on C6 glioma cells.
The outcome of this study evidently demonstrates that C6 glioma cells co-cultured with increased concentration of WFA, showed an anti-proliferative, anti-inflammatory and pro-apoptotic effect in a dose-dependent fashion.
Medicinal herbs in Ayurveda have been widely used for thousands of years to promote health and treat diseases. Ayurvedic texts cover about 2000 species of plants with their medicinal uses as described by ancient Indian medical scholars. The active constituents in these plants are rightly balanced within the plants, and any possible untoward or toxic effects of one component would be neutralized by the presence of complementary constituents. However, many Ayurvedic herbs in use today are based on the principle of single-chemical isolation from plants or large-scale synthesis, and in many instances, these single-chemical entities elicit adverse effects when used alone. However, limited evidence is available to testify the safety and efficacy of Ayurvedic herbs. An integrated approach for safety assessment focused on the hazard identification is imperative. In this context, we will be discussing the safety and efficacy of Ashwagandha (Withania somnifera), known for its adaptogenic property.
Huntington's disease (HD) is a neurological disorder characterized by abnormal body movements (chorea) associated with cognitive and motor dysfunctions, neuropsychiatric disturbances, and striatal damage. 3-Nitropropionic acid (3-NP) triggers cellular energy deficit, nitric oxide (NO) mechanisms, and oxidative stress (OS)-induced neurotoxicity by inhibiting the activity of mitochondrial complex II enzyme and succinate dehydrogenase in irreversible fashion. Chronic systemic administration of 3-NP to animals produces preferential degeneration of the striatum, leading to motor and cognitive deficits, closely resembling HD. Besides 3-NP model of striatal neurodegeneration, a number of transgenic animal models expressing mutant proteins are routinely used in preclinical trials exploring anti-HD therapeutics. In this review, the roles of a number of plant extracts, fractions, and isolated compounds investigated in various neurotoxic animal models and transgenics are discussed, highlighting on their ability to influence signaling pathways, leading to neuromodulation and probable neuroprotection. Since mitochondrial involvement and OS are also common phenomena in etiopathogenesis of a number of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), a few plant-based anti-HD natural products have been found efficacious against such diseases. Therapeutic advancement in screening of natural products against HD suffers from constraints such as limited animal models and giving maximum emphasis on cellular models during experimentations. However, recent progress in animal HD transgenic models expressing mutant proteins may reveal the therapeutic efficacy of natural products against HD, a disease with less elucidated pathogenesis and inadequate treatment strategies.
The present study aimed to investigate the efficacy of the herb ashwagandha in the prevention of stressinduced alterations in the ovary. Exposure of rats to two stressors i.e. restraint (1 h), then after a gap of 4 h to forced swimming exercise (15 minutes) every day for 4 weeks resulted in a significant increase in the adrenocortical activity, indicating the activation of hypothalamo-pituitary-adrenal axis. Concomitantly, there was a decrease in the weight, activities of 3β-hydroxysteroid dehydrogenase and antioxidant enzymes, number of healthy antral follicles, corpora lutea and percentage of healthy granulosa cells of the ovary, whereas the number of atretic follicles, the percentage of apoptotic granulosa cells and malondialdehyde concentration of the ovary showed an increase in the stressed rats compared to those of controls. However, stressed rats pre-treated with the alcoholic extract of ashwagandha (10mg/ kg body weight, oral) did not show these adrenal and ovarian stress responses and did resemble controls. The results for the first time reveal that an extract of ashwagandha is potent enough to inhibit activation of hypothalamo-pituitary-adrenal axis and maintain normal gametogenic and antioxidant activities of the ovary under stressful conditions.
Withania somnifera, commonly known as Ashwagandha, is a herb used in the Indian Ayurvedic medical system for centuries for its health benefits in wide range of conditions. It has been documented to enhance the functions of the nervous system and improves cognition. Medicinal properties of Withania somnifera are primarily attributed to the presence of active constituents known as withanolides. The multimodal beneficial effects of WS and its constituents stem from its property to act as an anti-oxidant, anti-inflammatory, anti-cancer, hemopoietic and rejuvenating agent. WS has been shown to have beneficial role in many neurological conditions that include Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, anxiety disorders, cerebral ischemia. However, the mechanisms involved in the beneficial effects of WS have not been well understood. The article provides information on the mechanisms involved in neuroprotective ability of WS in preventing various neurodegenerative conditions.
Despite continued effort for last few decades, there are no effective therapies available to treat amyotrophic lateral sclerosis (ALS). This is, in part, due to the multi-factorial nature of the disease, which makes it difficult to treat with a single drug targeted at a specific factor, pathway or mechanism. In the ensuing chapter, we discuss the potential therapeutic action of Withania somnifera extracts in ALS pathogenesis. Withania somnifera, which is commonly known as Ashwagandha, has been used in traditional medical systems in India, China and some middle-eastern countries for the past 3000 years. The most common use of the plant extract is as a rejuvenator, but it also possesses potent anti-inflammatory, anti-oxidant, anti-neoplastic, and immunomodulatory properties. Based on these, the plant extract has been used in numerous diseases, including neurodegenerative diseases, with various degrees of efficacy. In this chapter, we shall present the rationale for considering Withania somnifera and its constituents as therapeutic possibility in ALS.
This review presents an overview of published studies for a better understanding of the anti-mutagenic potential of medicinal plants and the precise indications for the utilization of natural compounds as chemo-preventive agents. Reports on the anti-mutagenic potential of medicinal plants published from 1997 to 2019 were searched through different scientific databases using the following keywords: medicinal plants and mutagens, carcinogens, the anti-mutagenic potential of medicinal plants. The data relevant to the anti-mutagenic potential of some common medicinal plants is summarized in this mini-review. These medicinal plants include Carum carvi, Withania somnifera, Panax ginseng, Mentha spicata, Curcuma zedoaria, Cassia angustifolia, Cymbopogon citrates, Ipomoea batatas, Glycyrrhiza glabra, Citrullus colocynthis, Capsicum annuum and Asparagus racemosus. An overview of the identified molecules or enzymes being targeted is also presented, with a focus on anti-carcinogenic and/or anti-mutagenic activity. The recent advancements in the research on medicinal plants pave the way for the better understanding and future prospects of the use of natural components as chemo-preventive and chemotherapeutic agents.
Rapidly growing population, social and environmental factors are continuously exerting impact on social and psychological human health in multiple ways. In particular, these factors cause cumulative stress affecting cognitive functions and elevate risks of diverse neuronal dysfunction and malignant brain diseases. Maintenance of brain health has hence emerged as a new challenge in increasing old age populations worldwide. Use of herbal drug constituents has emerged as a preferred choice due to enormous undesirable side effects of pharmacological drugs. Ashwagandha, a sub-tropical medicinal plant has been extensively used in Indian traditional home medicine system i.e. called “Ayurveda” for its stress-, hypertension-, aging-, neurological dysfunction- and malignant growth-inhibitory properties. Detailed molecular insights of these activities and mechanism(s) are only beginning to be demonstrated by laboratory studies. In this chapter, we attempt to sketch research evidence of the benefits of Ashwagandha bioactives for brain health.
This study involves a detailed investigation about the effect of three elicitors, such as chitosan, jasmonic acid and salicylic acid (SA) on withaferin A and withanolide A contents of Withania somnifera (L.) Dunal (Poshita variety). Moreover, the different environmental regimes were also studied to assess and optimise the accumulation of withaferin A and Withanolide A contents. In an open environment, the total withaferin A content was found to be increased 6.3 and 5.8 times when sprayed with chitosan, 10 ppm and 50 ppm, respectively, as compared to control. Similarly, the total withanolide A content was found to be increased 4.5 and 3.6 times when sprayed with jasmonic acid (400 ppm and 200 ppm, respectively) with respect to control. In a controlled condition, the total withaferin A content was found to be increased 6 and 4.5 times when sprayed with jasmonic acid (400 ppm and 200 ppm, respectively) as compared to control. On the other hand, the total withanolide A content was found to be enhanced by 7 and 4.3 times when sprayed with jasmonic acid (400 ppm) and SA (1 ppm), respectively, as compared to control. Therefore, this study was focussed on the optimisation of enhanced accumulation of withaferin A and withanolide A contents in the aerial parts of the plant in open and controlled environment by foliar application of elicitors in minimal concentrations.
Withania somnifera (L.) (family-Solanaceae), known as ‘Indian ginseng’ or ‘Ashwagandha’ is acclaimed as an effective adaptogen, immunomodulator, aphrodisiac and sedative. Ashwagandha ghrita is a recognized ghee based Ayurvedic formulation. Few ancient texts suggest murcchana process for preparation of Ashwagandha ghrita.
The study was undertaken to evaluate probable effects of murcchana process on ghrita preparation with reference to time and storage conditions.
Materials and Methods
Ashwagandha ghrita samples were prepared separately using plain ghee (Indian cow's ghee) and murcchana ghee. These formulations were stored separately in different glass bottles at room temperature and 400C/75%RH. Organoleptic characters (colour, odour, taste, texture and touch) and physicochemical parameters (acid value, peroxide value, iodine value, saponification value, unsaponifiable matter, refractive index and specific gravity) were determined after 3, 6, 9 and 12 months. Plain ghee and prepared ghrita were subjected for antioxidant evaluation by various in vitro methods.
Changes were observed in organoleptic characters and physicochemical parameters of plain ghee and Ashwagandha ghrita formulations. Alterations in these parameters were more pronounced at high temperature and on long storage. Ashwagandha ghrita prepared with murcchana process exhibited better antioxidant potential in all in vitro methods.
The murcchana process was found to be beneficial towards quality of ghrita. Hence, Ashwagandha ghrita may be prepared along with murcchana herbs and stored in a good quality glass bottle to ensure improved shelf life of ghrita.
Systemic inflammation driven neuroinflammation is an event which correlates with pathogenesis of several neurodegenerative diseases. Therefore, targeting peripheral and central inflammation simultaneously could be a promising approach for the management of these diseases. Nowadays, herbal medicines are emerging as potent therapeutics against various brain pathologies. Therefore, in this contemporary study, the neuroprotective activity of Ashwagandha (Withania somnifera) was elucidated against the inflammation associated neurodegeneration and cognitive impairments induced by systemic LPS administration using in vivo rat model system.
To achieve this aim, young adult wistar strain male albino rats were randomized into four groups: (i) Control, (ii) LPS alone, (iii) LPS + ASH-WEX, (iv) ASH-WEX alone. Post regimen, the animals were subjected to Rotarod, Narrow Beam Walking and Novel Object Recognition test to analyze their neuromuscular coordination, working memory and learning functions. The rats were then sacrificed to isolate the brain regions and expression of proteins associated with synaptic plasticity and cell survival was studied using Western blotting and Quantitative real time PCR. Further, neuroprotective potential of ASH-WEX and its active fraction (FIV) against inflammatory neurodegeneration was studied and validated using in vitro model system of microglial conditioned medium-treated neuronal cultures and microglial-neuronal co-cultures.
Orally administered ASH-WEX significantly suppressed the cognitive and motor-coordination impairments in rats. On the molecular basis, ASH-WEX supplementation also regulated the expression of various proteins involved in synaptic plasticity and neuronal cell survival. Since microglial-neuronal crosstalk is crucial for maintaining CNS homeostasis, the current study was further extended to ascertain whether LPS-mediated microglial activation caused damage to neurons via direct cell to cell contact or through secretion of inflammatory mediators. ASH-WEX and FIV pretreatment was found to restore neurite outgrowth and protect neurons from apoptotic cell death caused by LPS-induced neuroinflammation in both activated microglial conditioned medium-treated neuronal cultures as well as microglial-neuronal co-cultures.
This extensive study using in vivo and in vitro model systems provides first ever pre-clinical evidence that ASH-WEX can be used as a promising natural therapeutic remedial for the prevention of neurodegeneration and cognitive impairments associated with peripheral inflammation and neuroinflammation.
Post-traumatic stress disorder (PTSD) is precipitated by exposure to severe traumatic events such as wars, natural disasters, catastrophes, or other traumatic events. Withania somnifera (WS) Dunal (family: Solanaceae) known traditionally as “Ashwaghanda” is used widely in ayurvedic medicine, and known to have positive role in neurodegenerative diseases. In this study, WS effect on impairment of memory due to PTSD was studied in animal models. Single-prolonged stress rat model, which consisted of restrain for 2 h, forced swimming for 20 min, rest for 15 min, and diethyl ether exposure for 1–2 min, was used to induce PTSD animals. The WS root powder extract was administered orally at a dose of 500 mg/kg/day. The radial arm water maze (RAWM) was used to assess spatial learning and memory. Enzymatic assays were used to evaluate changes in oxidative stress biomarkers in the hippocampus following treatments. The result showed that PTSD resulted in short- and long- term memory impairments. Administration of WS prevented this impairment of memory induced by PTSD. Furthermore, WS prevented PTSD induced changes in oxidative stress biomarker in the hippocampus. For quality assessment, the methanolic extract for WS was subjected to UHPLC analysis. A calibration curve for isowithanone as a marker compound was constructed. WS roots content of isowithanone was found to be 0.23% (w/w). In conclusion, WS administration prevented PTSD induced memory impairment probably through preserving changes in antioxidant mechanisms in the hippocampus.
The rapid emergence of multi-drug resistant bacteria and reduced susceptibility of bacteria to antibiotics adds urgency to search for new compounds having noticeable action on new and re-emerging infectious diseases. Withania somnifera is a remarkable source of new therapeutic agents for antimicrobial activity as well as antioxidant activity. The root powder of Withania somnifera was extracted sequentially with hexane, chloroform and methanol, by both hot and cold extraction method. In vitro antibacterial activity of extract was screened against both gram-negative and gram-positive bacteria. The chloroform extract of Withania somnifera root showed significant antibacterial activity against Staphylococcus aureus and Salmonella typhi. The methanol extract showed comparable antioxidant potential with ascorbic acid (standard compound). These extracts were analyzed structurally and qualitatively, to identify the phytocompounds responsible for the activity. The antimicrobial potential of major phytoconstituents was screened using docking software AutoDock 4 against a target protein topoisomerase IV type B. It was found that withasomnine was an efficient antibacterial compound which showed significant inhibition with minimum docking energy − 6.22 kJ mol⁻¹, binding energy − 10.07 kJ mol⁻¹ and inhibition constant 4.14e−008. This was the first report on the antimicrobial docking studies on withasomnine by proving its antimicrobial activity.
Abstract Modern studies have shown that adaptogens can non-specifically enhance the resistance of human body under a wide range of external stress conditions with a multi-targeted and multi-channel network-like manner, especially by affect the immune-neuro-endocrine system and the hypothalamic–pituitary–adrenal axis. This review article draws the attention to the relationships of adaptogens, tonics from traditional Chinese medicine (TCM) and ginseng-like herbs worldwide, which all have similar plant sources and clinical applications. To clarify the sources and pharmacological mechanisms of these plant-originated adaptogens, which will provide useful information for the utilization of adaptogens to improve the human health. Meanwhile, the TCMs and the world-wide ginseng-like herbs from each region’s ethnopharmacology will be beneficial modernization and globalization.
Reactive gliosis, microgliosis, and subsequent secretion of various inflammatory mediators like cytokines, proteases, reactive oxygen, and nitrogen species are the suggested key players associated with systemic inflammation-driven neuroinflammation and cognitive impairments in various neurological disorders. Conventionally, non-steroidal anti-inflammatory drugs are prescribed to suppress inflammation but due to their adverse effects, their usage is not well accepted. Natural products are emerging better therapeutic agents due to their affordability and inherent pleiotropic biological activities. In Ayurveda, Ashwagandha (Withania somnifera) is well known for its immunomodulatory properties. The current study is an extension of our previous report on in vitro model system and was aimed to investigate anti-neuroinflammatory potential of water extract from the Ashwagandha leaves (ASH-WEX) against systemic LPS-induced neuroinflammation and associated behavioral impairments using in vivo rat model system. Oral feeding of ASH-WEX for 8 weeks significantly ameliorated the anxiety-like behavior as evident from Elevated plus maze test. Suppression of reactive gliosis, inflammatory cytokines production like TNF-α, IL-1β, IL-6, and expression of nitro-oxidative stress enzymes like iNOS, COX2, NOX2 etc were observed in ASH-WEX-treated animals. NFκB, P38, and JNK MAPKs pathways analysis showed their involvement in inflammation suppression which was further confirmed by inhibitor studies. The current study provides first ever preclinical evidence and scientific validation that ASH-WEX exhibits the anti-neuroinflammatory potential against systemic LPS-induced neuroinflammation and ameliorates associated behavioral abnormalities. Aqueous extract from Ashwagandha leaves and its active phytochemicals may prove to be promising candidates to prevent neuroinflammation associated with various neuropathologies.
Withania somnifera is wonder shrub used traditionally as a folk medicine for several remedies in the Indian subcontinent. During last few decades numerous scientific studies have shown the potential therapeutic prospects of this herb and of its various constituents in different disease models. Several classes of compounds including withanolides, sitoindosides and other useful alkaloids have been isolated from this plant with promising medicinal value. It has been demonstrated that different parts of plant including roots, leaves and fruits exhibit unique biological activities that actually are manifested to the presence and the abundance of specific constituent/s in the respective parts of the plant. It was also established that same plant grown at different locations under varied environmental conditions influences the synthesis of the individual constituents in different parts of the plant, hence their biological activities. Studies conducted in cellular and murine models have shown that extracts made of roots bear immune activating properties, whereas leaf extracts showed anticancer activities. It has been observed that root and leaf extracts of plant characterised with about a dozen markers displayed that root extracts demonstrated Th1 specific immunomodulatory and anti-inflamatory activities, whereas leaf extracts showed anticancer properties, respectively. It was further explored that anti-cancer potential of leaf extracts was mainly due to Withaferin A, a potent cytotoxic withanoloid, existing in abundance and a major constituent in the leaves of the plant. Similarly, anti-inflammatory and Th1 immune skewing properties of the root extract was conferred to the higher amount of Withanolide A, present in the roots of the plant along with other constituents. Meanwhile several studies have deciphered the role of individual constituents in various biological activities with extensive mechanism of action discussed in this review. This review while summarises the potential medicinal benefits of the W.somnifera, it also emphasizes that marketed product of the plant extracts for human consumption should scientifically validated for bioactive constitutents.
Ayurvedic medicine is a personalized system of traditional medicine native to India and the Indian subcontinent. It is based on a holistic view of treatment which promotes and supports equilibrium in different aspects of human life: the body, mind, and soul. Popular Ayurvedic medicinal plants and formulations that are used to slow down brain aging and enhance memory include Ashwagandha (Withania somnifera) , Turmeric (Curcuma longa) , Brahmi (Bacopa monnieri) , Shankhpushpi ( Convolvulus pluricaulis, Evolvulus alsinoides , and other species), gotu kola (Centella asiatica) , and guggulu ( Commiphora mukul and related species) and a formulation known as Brāhmī Gh ṛ ita, containing Brahmi, Vacā (Acorus calamus) , Ku ṣṭ ha (Saussurea lappa) , Shankhpushpi, and Purāṇa Gh ṛ ita (old clarified butter/old ghee). The rationale for the utilization of Ayurvedic medicinal plants has depended mostly on traditional usage, with little scientific data on signal transduction processes, efficacy, and safety. However, in recent years, pharmacological and toxicological studies have begun to be published and receive attention from scientists for verification of their claimed pharmacological and therapeutic effects. The purpose of this review is to outline the molecular mechanisms, signal transduction processes, and sites of action of some Ayurvedic medicinal plants. It is hoped that this description can be further explored with modern scientific methods, to reveal new therapeutic leads and jump-start more studies on the use of Ayurvedic medicine for prevention and treatment of dementia.
Ayurveda is the most ancient and the traditional medicinal system with historical roots in the Indian subcontinent. Modernized practices derived from traditional Ayurvedic medicinal system are a type of complementary or alternative medicine (Jafari et al. 2014). High costs and increased side effects of new drugs, lack of curative treatment for several chronic diseases, and microbial resistance are some of the reasons that have contributed in directing the public interest towards complementary and alternative medicine. Ayurvedic therapies have been integrated in complementary and alternative medicine as preventive measures to treat wide range of chronic diseases due to their least adverse effects compared to conventional medicines (Humber 2002; Patwardhan et al. 2004; Jafari et al. 2014). Moreover, Ayurveda formulations may also be used in combination with other drugs without any adverse drug-drug interactions (Humber 2002; Patwardhan et al. 2004). The concept of “one drug-one target-one disease” in modern medicines has provided remarkable success in providing highly selective and potent magic bullets, especially for certain highly contagious diseases. In several other diseases especially lifestyle disorders, this approach has shown major disadvantages where a disease manifestation and progression involve multifactorial and complex signaling pathways. Herbal products are being actively used as means of alternative medicine because of their multicomponent approach to target multiple sites for their mode of action (Bent and Ko 2004; Tachjian et al. 2010; Pallas et al. 2013). Moreover, their formulation in single delivery system and their least side effects make them promising candidates to treat several central nervous system ailments (Borisy et al. 2003; Keith et al. 2005). Furthermore, these herbal formulations can be used in combination with other drugs without any adverse drug-drug interactions (Hopkins 2008).
Withania somnifera, commonly known as "Ashwagandha" or "Indian ginseng" is an essential therapeutic plant of Indian subcontinent regions. It is regularly used, alone or in combination with other plants for the treatment of various illnesses in Indian Systems of Medicine over the period of 3,000 years. Ashwagandha (W. somnifera) belongs to the genus Withania and family Solanaceae. It comprises a broad spectrum of phytochemicals having wide range of biological effects. W. somnifera has demonstrated various biological actions such as anti-cancer, anti-inflammatory, anti-diabetic, anti-microbial, anti-arthritic, anti-stress/adaptogenic, neuro-protective, cardio-protective, hepato-protective, immunomodulatory properties. Furthermore, W. somnifera has revealed the capability to decrease reactive oxygen species and inflammation, modulation of mitochondrial function, apoptosis regulation and improve endothelial function. Withaferin-A is an important phytoconstituents of W. somnifera belonging to the category of withanolides been used in the traditional system of medicine for the treatment of various disorders. In this review, we have summarized the active phytoconstituents, pharmacologic activities (preclinical and clinical), mechanisms of action, potential beneficial applications, marketed formulations and safety and toxicity profile of W. somnifera.
The epidemic of obesity has reached alarming levels in both developing and developed nations. Excessive calorie intake and sedentary lifestyle due to technological advancements are the main causal factors for overweight and obesity among the human population. Obesity has been associated with a number of co-morbidities such as hypertension, type 2 diabetes mellitus, cardiovascular diseases, and neurodegeneration and dementia. The progression of neurological disorders in obese subjects has been mainly attributed to neuroinflammation. Withania somnifera has been used in numerous Ayurvedic formulations owing to its wide array of health-promoting properties. The current study was designed to test the hypothesis whether dry leaf powder of W. somnifera has anxiolytic and anti-neuroinflammatory potential in diet-induced obesity.
Young adult female rats were divided into four groups: low fat diet group (LFD) fed with regular chow feed, high fat diet group (HFD) fed with diet containing 30% fat by weight, low fat diet plus extract group (LFDE) fed with regular chow feed supplemented with dry leaf powder of W. somnifera 1 mg/g of body weight (ASH), and high fat diet plus extract group (HFDE) fed with diet containing 30% fat by weight and supplemented with ASH. All the animals were kept on respective feeding regimen for 12 weeks; following which, the animals were tested for their anxiety-like behavior using elevated plus maze test. The animals were sacrificed and used to study various inflammatory markers such as GFAP, Iba1, PPARγ, iNOS, MCP-1, TNFα, IL-1β, IL-6, and various markers of NF-κB pathway by Western blotting and quantitative real-time PCR. Serum levels of leptin, insulin and pro-inflammatory cytokines were also assayed.
ASH treated rats showed less anxiety levels as compared to HFD animals. At molecular level, ASH ameliorated the HFD-induced reactive gliosis and microgliosis and suppressed the expression of inflammatory markers such as PPARγ, iNOS, MCP-1, TNFα, IL-1β, and IL-6. Further, ASH ameliorated leptin and insulin resistance and prevented HFD-induced apoptosis.
Dry leaf powder of W. somnifera may prove to be a potential therapeutic agent to attenuate neuroinflammation associated with obesity and may prevent its co-morbidities.
Withania somnifera (WS) plant has been used for centuries to cure or treat various disorders in the Ayurvedic medicine. Research over the years has indicated that withanolides are the primary bioactive constituents in WS. Scientific evidence for anticancer effects of WS root extract (WRE) is quite strong, and is derived from both in vitro cellular experiments and in vivo studies in rodent models of cancer. This article reviews scientific evidence supporting anticancer effects of WRE and its primary withanolide (withaferin A). The primary focus of the present article is on: (a) phytochemistry of WS, (b) withanolide biosynthesis, (c) pharmacokinetics, (d) in vivo evidence for anticancer activity of WRE and its primary bioactive component withaferin A (WA), and (e) effect of WA and WRE on cancer stem cell population and/or epithelial-mesenchymal transition. Unpublished results from our own laboratory are presented to demonstrate that WA is the most likely primary anticancer agent in WRE standardized for WA content (sWRE). The mechanisms underlying anticancer effects of WRE and WA have been reviewed extensively by us and others, and therefore are not elaborated in this article.
The search for therapeutic candidates of memory disorders including gene targets and compounds both synthetic and natural has been a prime arena of neurobiology research. Amongst suggested therapeutic compounds, several herbal products with a long history of use in Ayurveda have gained attention in modern medicine. Ashwagandha (Withania somnifera) also referred to as “Queen of Ayurveda” is at the zenith of Ayurvedic herbs owing to its tremendous potential to recover memory decline in aging and neurodegenerative pathologies as well as enhance basal memory function of healthy individuals. Despite such promising effects, limited mechanistic evidences have hindered its acceptance in modern medicine. However, technical advances in neuroscience research over the past decade have filled-in some gaps in understanding of molecular and mechanistic biology of Ashwagandha effects. In this chapter, we highlight the studies that have deciphered the cellular and molecular mechanisms of memory enhancing potential of Ashwagandha in various disease models. Cellular targets of Ashwagandha include (i) activation of antioxidant defence system rescuing nerve cells from apoptosis, oxidative stress and DNA damage, (ii) induction of cholinergic system and (iii) up-regulation of memory linked neuroplasticity genes and neuronal arborisation. All of these molecular effects translate into increase in memory. Such multiple-module action has intrigued research to unravel upstream master regulators of Ashwagandha effects on gene expression, cell physiology and behaviour.
Ashwagandha (Withania somnifera), a traditional Indian herb, has been widely employed in ayurvedic medicine. Various compounds isolated from leaf and root of this plant are used in treating human illness ranging from weakness, anxiety, rheumatic pain, diabetes, infertility, oxidative stress to cancer. In past two decades, scientific evidence for the neuroprotective effect of Ashwagandha further validates its use for treatment of Alzheimer’s, Parkinson’s, Huntington’s disease and spinal cord injury. This chapter discusses the neuroprotective effects of various components of Ashwagandha in neurological disorders, majority of which have been studied using animal models or cell lines. Extensive explorations into mechanistic aspects of Ashwagandha are mandatory to validate the findings obtained from animal models and to confirm their therapeutic potential in human system. In order to explore the therapeutic potential of the drug for treating brain disorders, it is important to investigate the effects of this herbal drug on primary human brain cells. This chapter emphasizes on the potential of using human neural stem cells (NSCs) as an in vitro model to study the neuroprotective effects of Ashwagandha and to gain novel insights into the underlying mechanism of action under physiological and pathological conditions. Different sources of neural stem cells have also been described in the chapter with a detailed insight on the method of deriving NSCs.
Withania somnifera (WS) also known as ashwagandha is a well-known medicinal plant used in traditional medicine in many countries for infertility treatment. The present study was aimed at systemically reviewing therapeutic effects of WS on the reproductive system.
This systematic review study was designed in 2016. Required data were obtained from PubMed, Scopus, Google Scholar, Cochrane Library, Science Direct, Web of Knowledge, Web of Science, and manual search of articles, grey literature, reference checking, and expert contact.
WS was found to improve reproductive system function by many ways. WS extract decreased infertility among male subjects, due to the enhancement in semen quality which is proposed due to the enhanced enzymatic activity in seminal plasma and decreasing oxidative stress. Also, WS extract improved luteinizing hormone and follicular stimulating hormone balance leading to folliculogenesis and increased gonadal weight, although some animal studies had concluded that WS had reversible spermicidal and infertilizing effects in male subjects.
WS was found to enhance spermatogenesis and sperm related indices in male and sexual behaviors in female. But, according to some available evidences for spermicidal features, further studies should focus on the extract preparation method and also dosage used in their study protocols.
Ayurvedo-Herbal Medicines -The Need of the Time -Herbal Drugs, A twenty first century perspective. Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization (DRDO)
Singh, N. (2006). Ayurvedo-Herbal Medicines -The Need of the Time -Herbal Drugs, A twenty first century
perspective. Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization (DRDO),
Govt. of India, Delhi, 535-547.
Clinical Study of Organic Ashwagandha in cases of Parkinsonism, Neuropathy, Paralysis and Uterine Tumours (Fibroids and other tumours) including Cutaneous Endodermal Carcinoma
S S Abbas
Abbas, S.S, Singh, V., Bhalla, M., and Singh, N. (2004). Clinical Study of Organic Ashwagandha in cases of
Parkinsonism, Neuropathy, Paralysis and Uterine Tumours (Fibroids and other tumours) including Cutaneous Endodermal
Carcinoma. Proc., National Seminar on "Eco-friendly Herbs of Ayurveda in Healthcare of Mankind: A Strategy for Scientific
Evaluation an Uniform Standardization" -Lucknow, 81.
National Seminar on "Eco-friendly Herbs of Ayurveda in Healthcare of Mankind: A Strategy for Scientific Evaluation an Uniform Standardization
Parkinsonism, Neuropathy, Paralysis and Uterine Tumours (Fibroids and other tumours) including Cutaneous Endodermal
Carcinoma. Proc., National Seminar on "Eco-friendly Herbs of Ayurveda in Healthcare of Mankind: A Strategy for Scientific
Evaluation an Uniform Standardization" -Lucknow, 81.
A clinical study of Organic Ashwagandha in some cases of uterine tumors (fibroids) and dermatofibrosarcoma
S S Abbas
Abbas, S.S., Bhalla, M. and Singh, N. (2005). A clinical study of Organic Ashwagandha in some cases of uterine
tumors (fibroids) and dermatofibrosarcoma. Proc. workshop on essential medicines, adverse drug reactions and therapeutic
drug monitoring. Scientific Convention Centre, Lucknow, 143-144.
Effect of Withania somnifera, Panex ginseng and Cannabis indica and radio ligand binding with neurohumoral in the CNS
K S Dixit
A K Agarwal
P K Seth
Dixit, K.S., Agarwal, A.K., Seth, P.K. and Singh, N. (1995). Effect of Withania somnifera, Panex ginseng and
Cannabis indica and radio ligand binding with neurohumoral in the CNS, World Congress on Biotech. Dev. Med. Subs.
Plants & Marine Origin, King George Medical College, Lucknow (India), 141.
Effects of stress and anti-stress drugs on succinate dehydrogenase enzyme (SDH) in rat brain (A possible role of SDH in stress adaptation phenomenon) Physiology of Human Performance, Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization (DRDO)
G P Gupta
Kalsi, R., Singh, N. and Gupta, G.P. (1987). Effects of stress and anti-stress drugs on succinate dehydrogenase
enzyme (SDH) in rat brain (A possible role of SDH in stress adaptation phenomenon) Physiology of Human Performance,
Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization (DRDO), Govt. of
India, Delhi, 114-117.
Evaluation of 'adaptogenic' properties of Withania somnifera
A K Agarwal
R P Kohli
Singh, N., Agarwal, A.K., Lata, A. and Kohli, R.P. (1976). Evaluation of 'adaptogenic' properties of Withania
somnifera. Proc. Indian Pharmacological Society, 17.
Experimental evaluation of 'adaptogenic' properties of Withania somnifera
A K Agarwal
R P Kohli
Singh, N., Agarwal, A.K., Lata, A. and Kohli, R.P. (1977). Experimental evaluation of 'adaptogenic' properties of
Withania somnifera. XIIth Scientific Seminar on Indian Medicine, Institute of Medical Sciences. Varanasi. 4.
A new concept on the possible therapy of stress disease with 'Adaptogens' (Anti-stress drugs) of indigenous plant origin
Singh, N. (1981). A new concept on the possible therapy of stress disease with 'Adaptogens' (Anti-stress drugs) of
indigenous plant origin. Curr. Med. Prac., 25: 50-55.
Anti-stress plants as anti-rheumatic agents, 5 th Sepal Congress of Rheumatology
S P Singh
R P Kohli
K P Bhargava
Singh, N., Singh, S.P., Nath, C., Kohli, R.P. and Bhargava, K.P. (1984). Anti-stress plants as anti-rheumatic agents,
5 th Sepal Congress of Rheumatology, Bangkok, 37.
A Placebo Controlled Clinical Trial of Cyprus rotundus, Withania somnifera and their Combination in cases of Rheumatoid Arthritis
S P Singh
K S Dixit
R C Saxena
R P Kohli
Singh, N., Singh, S.P., Dixit, K.S., Saxena, R.C. and Kohli, R.P. (1986a). A Placebo Controlled Clinical Trial of
Cyprus rotundus, Withania somnifera and their Combination in cases of Rheumatoid Arthritis. Proc. International Seminar.,
2: 18 -21.
Stress disease and herbal medicine
Singh, N. (1995a). Stress disease and herbal medicine. World Congress on Biotech. Dev. Med. Subs. Plants &
Marine Origin, King George Medical College, Lucknow (India), 48.
Effect of Anti-stress agents on receptor population in rat brain
Singh, N. (1993b). Effect of Anti-stress agents on receptor population in rat brain, Inaugural issue of J. Biotech.
Med. Plant Res., Lucknow, 14.
Experimental methods tools for assessment of anti-stress activity in medicinal plants
Singh, N. and Misra, N. (1993). Experimental methods tools for assessment of anti-stress activity in medicinal
plants. Journal of Biomedical Research., 12(182): 124-127.
Anti-stress (Ayurvedic Plants) Ocimum sanctum (Tulsi) and Withania somnifera (Ashwagandha) in prevention and treatment of cardiovascular disorders
Singh, N. (1995b). Anti-stress (Ayurvedic Plants) Ocimum sanctum (Tulsi) and Withania somnifera
(Ashwagandha) in prevention and treatment of cardiovascular disorders. Proc. Vth W.C.C.N., China, 10.
Role of Adaptogens / Antistress agents of plant origin in health care & stress diseases of man
S S Abbas
Singh, N., Singh, V. and Abbas, S.S. (2003). Role of Adaptogens / Antistress agents of plant origin in health care &
stress diseases of man. Proc. 2 nd World Cong. Biotech. Dev. Herbal Med., Lucknow (India), 33.
Singh, N. (2005). Dilemma of Ayurvedic Herbal Medicines / Food Supplements Proc. workshop on Essential
Medicines, Adverse Drug Reactions and Therapeutic Drug Monitoring, Dept. of Pharmacology & Therapeutics, KGMU,
Scientific Convention Centre, Lucknow, 35-41.
Herbs -The Life of Man, Need Pharmaco-clinical Studies for their Scientific Validation -Relevance of Modern Methods of Pharmacological Studies to Traditional Medicine
Singh, N. (2008). Herbs -The Life of Man, Need Pharmaco-clinical Studies for their Scientific Validation -Relevance of Modern Methods of Pharmacological Studies to Traditional Medicine, Department of Pharmacology &
Therapeutics, C.S.M. Medical University, Scientific Convention Centre, Lucknow, 37-43.
Herbal Medicine -Science embraces tradition -a new insight into the ancient Ayurveda
Singh, N. and Gilca, M. (2010). Herbal Medicine -Science embraces tradition -a new insight into the ancient
Ayurveda, Lambert Academic Publishing (Germany), 51-67.
Tulsi 'The Mother Medicine of Nature' 2 nd Edition, International Institute of Herbal Medicine
Singh, N., Hoette, Y. and Miller, R. (2010) -Tulsi 'The Mother Medicine of Nature' 2 nd Edition, International
Institute of Herbal Medicine, Lucknow, 28-32.
Clinical and experimental studies on rasayana drugs and rasayana therapy. Special Research Monograph, Central Council for Research in Ayurveda and Siddha (CCRAS), Ministry of Health and Family Welfare
R H Singh
K N Udupa
Singh R.H., Udupa K.N. (1993) Clinical and experimental studies on rasayana drugs and rasayana therapy. Special
Research Monograph, Central Council for Research in Ayurveda and Siddha (CCRAS), Ministry of Health and Family
Welfare, New Delhi.
Ashwagandha, Vanaushadhi Nidharsika (Ayurvedic Pharmacopia), UP Sansthan
An experimental evaluation of anti-tumor activity of Withania somnifera (Ashwagandha) and "Geriforte
S P Singh
D R Singh
M L Gupta
R P Kohli
Singh, S.P., Singh, D.R., Gupta, M.L., Singh, N. and Kohli, R.P. (1979). An experimental evaluation of anti-tumor
activity of Withania somnifera (Ashwagandha) and "Geriforte." XI Annual Conf. IPS. Ind. Jour. Pharmacol 11(1): 65.
Two new wichanolides named coagulin [17beta,27-dihydroxy-14,20-epoxide-1-oxo-(22R)-witha-3,5,24-trienolide]  and withasomidienone [27-hydroxy-3-oxo-(22R)-witha-1,4,24-trienolide]  have been isolated from Withania coagulance and Withania somnifera, respectively. The structures have been determined on the basis of spectroscopic studies.
Abstract Withania somnifera (L.) Dunal was evaluated for its tumor-preventing activity against urethane-induced lung adenomas in adult male albino mice. Administration of urethane in a dose of 125 mg/kg given subcutaneously biweekly for 7 months induced lung adenomas in 100% of animals. Urethane was also found to cause significant decrease in body weight, increase in mortality, leucopaenia and decrease in lymphocyte percentage as compared to untreated controls. Simultaneous oral administration of W. somnifera given in a dose of 200 mg/kg daily along with urethane protected the animals from the tumor-inducing effect of urethane. It also prevented the decrease in body weight and increase in mortality caused by urethane. The haematological changes were found to be completely reversed as evidenced by significant increases in total leucocyte count and lymphocyte percentage. These haematological changes were also observed in the animals treated with W. somnifera alone. It appears that W. somnifera may be preventing urethane-induced lung adenomas by inducing a state of nonspecific increase in resistance (adaptogen) and immunostimulant properties.
Abstract It was found that the extracts of Myrtus communis, Peganum harmala and Withania somnifera exhibited significant activities in either the hot-plate test or in benzoquinone and/or acetic acid-induced writhing in mice. The extracts of Artemisia herba-alba. Anchusa italica. Vicoo pentanema and Quercus infectoria failed to produce significant effects in either test at the doses used.
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.
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.
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.
Ultrastructural studies of biopsied cortical tissue from the right frontal lobe of 8 patients with mild to moderate Alzheimer's disease (AD) revealed that the number of synapses in lamina III of Brodmann's area 9 was significantly decreased when compared with the number in age-matched control brains (n = 9; postmortem time, less than 13 hours). Further decline in synaptic number was seen in age-matched autopsied AD specimens. In the AD brains there was significant enlargement of the mean apposition length, which correlated with degree of synapse loss; as synapse density declined, synapse size increased. The enlargement of synapses, coupled with the decrease in synaptic number, allowed the total synaptic contact area per unit volume to remain stable in the patients who underwent biopsy. In autopsied subjects who had AD, there was no further enlargement of mean synaptic contact area. There was a significant correlation between synapse counts and scores on the Mini-Mental State examination in the patients who underwent biopsy. Lower mental status scores were associated with greater loss of synapses. Choline acetyltransferase activity was significantly decreased in the biopsied group and declined further in the autopsied specimens of AD. There was no relationship between choline acetyltransferase activity and scores on the Mini-Mental State examination or synapse number. There is evidence of neural plasticity in the AD neuropil; synaptic contact size increased in patients who had biopsy and possibly compensated for the numerical loss of synapses. But by end stage of the disease, the ability of the cortex to compensate was exceeded and both synapse number and synaptic contact area declined.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of W. somnifera on glycosaminoglycan synthesis in the granulation tissue of carrageenin-induced air pouch granuloma was studied. W. somnifera was shown to exert significant inhibitory effect on incorporation of 35S into the granulation tissue. The uncoupling effect on oxidative phosphorylation (ADP/O ratio reduction) was also observed in the mitochondria of granulation tissue. Further, Mg2+ dependent ATPase activity was found to be influenced by W. somnifera. W. somnifera also reduced the succinate dehydrogenase enzyme activity in the mitochondria of granulation tissue.
There is now ample evidence for long-term malfunctioning within five different brain GABAergic pathways in a monkey model for tardive dyskinesia (TD). Three of these GABA connections (GPe-STN, CP-SNr, and CP-GPi) are chronically downregulated during neuroleptic treatment and after some years they do not seem to regain their normal activity, even when the neuroleptics are discontinued. The persistent downregulation of these three GABA connections, evidenced by depressions of terminal GAD activity and GABA levels, appears to be a conceivable mechanism behind tardive parkinsonism (TP), often reported to coexist with TD in the clinic. The TD patients' well-known lack of awareness of their symptoms may be due to their parkinsonian "sensory neglect." Another two GABA malfunctioning connections were found in our monkey model: SNr-VA/VL and GPi-VA/VL. These pathways are upregulated during chronic neuroleptic treatment, partly due to an elevated glutamate release within subthalamofugal pathways. This chronic glutamatergic hyperactivity may have acted via an excitotoxic mechanism and consequently both GPi and VA/VL had a low synaptic activity in our dyskinetic monkeys, as measured by 2-deoxyglucose uptake, even 4 months after the last neuroleptic dose. It is hypothesized that TD may be due to an excitotoxic lesion of the inhibitory GABAergic VA/VL afferents, while TP has to do with persistent malfunctioning of downregulated SNr and GPi afferents.
Withania somnifera is an Indian medicinal plant used widely in the treatment of many clinical conditions in India. Its antistressor properties have been investigated in this study using adult Wistar strain albino rats and cold water swimming stress test. The results indicate that the drug treated animals show better stress tolerance.
Ayurveda, the Indian system of traditional medicine, uses a concoction of several spices, herbs and minerals for the treatment of diseases. In a clinical prospective study we have evaluated the efficacy of Ayurveda treatment (a concoction in cow's milk of powdered Mucuna pruriens and Hyoscyamus reticulatus seeds and Withania somnifera and Sida cordifolia roots) in 18 clinically diagnosed (with a mean Hoen and Yahr value of 2.22) parkinsonian patients. As per Ayurveda principles, 13 patients underwent both cleansing (for 28 days) and palliative therapy (56 days), 5 patients underwent palliative therapy alone (84 days). Only the former group showed significant improvement in activities of daily living (ADL) and on motor examination as per UPDRS rating. Symptomatically, they exhibited better response in tremor, bradykinesia, stiffness and cramps as compared to the latter group. Excessive salivation worsened in both the groups. Analyses of powdered samples in milk, as administered in patients, revealed about 200 mg of L-DOPA per dose. The study establishes the necessity of cleansing therapy in Ayurveda medication prior to palliative therapy. It also reveals contribution of L-DOPA in the recovery as observed in Parkinson' disease following Ayurveda medication.
The objective of this paper is to review the literature regarding Withania somnifera (ashwagandha, WS) a commonly used herb in Ayurvedic medicine. Specifically, the literature was reviewed for articles pertaining to chemical properties, therapeutic benefits, and toxicity.
This review is in a narrative format and consists of all publications relevant to ashwagandha that were identified by the authors through a systematic search of major computerized medical databases; no statistical pooling of results or evaluation of the quality of the studies was performed due to the widely different methods employed by each study.
Studies indicate ashwagandha possesses anti-inflammatory, antitumor, antistress, antioxidant, immunomodulatory, hemopoietic, and rejuvenating properties. It also appears to exert a positive influence on the endocrine, cardiopulmonary, and central nervous systems. The mechanisms of action for these properties are not fully understood. Toxicity studies reveal that ashwagandha appears to be a safe compound.
Preliminary studies have found various constituents of ashwagandha exhibit a variety of therapeutic effects with little or no associated toxicity. These results are very encouraging and indicate this herb should be studied more extensively to confirm these results and reveal other potential therapeutic effects. Clinical trials using ashwagandha for a variety of conditions should also be conducted.
The effect of lyophilized aqueous extract of Cynomorium coccineum and Withania somnifera on testicular development and on serum levels of testosterone, ICSH and FSH was studied in immature male Wistar rats. There was a notable increase in testicular weight of animals treated with both extracts. Histological examination revealed an apparent increase in the diameter of seminiferous tubules and the number of seminiferous tubular cell layers in the testes of treated rats as compared with control ones. Extracts of both plants elicited notable spermatogenesis in immature rats but C. coccineum was more effective than W. somnifera in that respect. Serum testosterone and FSH levels were lower in animals treated with plants extracts than controls, whereas ICSH levels was higher in treated animals, specially in those treated with C. coccineum. It was concluded that extracts of both plants have a direct spermatogenic influence on the seminiferous tubules of immature rats presumably by exerting a testosterone-like effect.
We have utilised laser confocal microscopy to categorise β-amyloid plaque types that are associated with preclinical and end-stage Alzheimer’s disease and to define the neurochemistry of dystrophic neurites associated with various forms of plaques. Plaques with a spherical profile were defined as either diffuse, fibrillar or dense-cored using Thioflavin S staining or immunolabelling for β-amyloid. Confocal analysis demonstrated that fibrillar plaques had a central mass of β-amyloid with compact spoke-like extensions leading to a confluent outer rim. Dense-cored plaques had a compacted central mass surrounded by an outer sphere of β-amyloid. Diffuse plaques lacked a morphologically identifiable substructure, resembling a ball of homogeneous labelling. The relative proportion of diffuse, fibrillar and dense-cored plaques was 53, 22 and 25% in preclinical and 31, 49 and 20% in end-stage Alzheimer’s disease cases, respectively. Plaque-associated dystrophic neurites in preclinical cases were immunolabelled for neurofilament proteins whereas, in end-stage cases, these abnormal neurites were variably labelled for tau and/or neurofilaments. Double labelling demonstrated that the proportion of diffuse, fibrillar and dense-cored plaques that were neuritic was 12, 47 and 82% and 24, 82 and 76% in preclinical and end-stage cases, respectively. Most dystrophic neurites in Alzheimer’s disease cases were labelled for either neurofilaments or tau, however, confocal analysis determined that 30% of neurofilament-labelled bulb-like or elongated neurites had a core of tau immunoreactivity.
At the present, medication of dementia is limited to symptomatic treatments such as the use of cholinesterase inhibitors. To cure dementia completely, that is regaining neuronal function, reconstruction of neuronal networks is necessary. Therefore, we have been exploring antidementia drugs based on reconstructing neuronal networks in the damaged brain and found that withanoside IV (a constituent of Ashwagandha; the root of Withania somnifera) induced neurite outgrowth in cultured rat cortical neurons. Oral administration of withanoside IV (10 micromol/kg/day) significantly improved memory deficits in Abeta(25-35)-injected (25 nmol, i.c.v.) mice and prevented loss of axons, dendrites, and synapses. Sominone, an aglycone of withanoside IV, was identified as the main metabolite after oral administration of withanoside IV. Sominone (1 microM) induced axonal and dendritic regeneration and synaptic reconstruction significantly in cultured rat cortical neurons damaged by 10 microM Abeta(25-35). These data suggest that orally administrated withanoside IV may ameliorate neuronal dysfunction in Alzheimer's disease and that the active principle after metabolism is sominone.
Rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) are popular tisanes in their native South Africa and have a growing worldwide market. Both herbal teas are used traditionally for medicinal purposes and are rich in polyphenols with rooibos a rare source of the dietary dihydrochalcones, aspalathin and nothofagin. The principal polyphenols in honeybush include the xanthone mangiferin and the flavonones hesperitin and isokuranetin. Despite their divergent phytochemical and nutrient compositions, rooibos and honeybush share potent antioxidant and antimutagenic activities in vitro. Animal model studies indicate both herbal teas possess potent antioxidant, immune-modulating and chemopreventive actions. However, human studies of rooibos are limited and of honeybush are absent. No adverse effects of rooibos or honeybush consumption as tisanes have been reported.