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Withania somnifera (Indian ginseng) in diabetes mellitus: A systematic review and meta‐analysis of scientific evidence from experimental research to clinical application
Phytotherapy Research
Abstract
Withania somnifera Dunal, also known as Indian ginseng, has been in use since ancient times in the management of diabetes mellitus (DM). This systematic review and meta‐analysis evaluated the efficacy/effectiveness, safety and tolerability of W. somnifera in managing DM. Literature search (published/unpublished) was performed from inception to April 2019 in guidelines recommended databases. A total of 6 in‐vitro, 13 pre‐clinical and 5 clinical studies were included for systematic evaluation. W. somnifera treatment in DM significantly restored the altered levels of blood glucose (experimental data; mean difference, −196.27; 95% confidence interval [−220.96, −171.58]; p < .00001) glycosylated haemoglobin (HbA1c), insulin, lipid profile, serum and oxidative stress markers with no safety concerns. The results suggest the potential role of W. somnifera in managing DM. However, the available clinical data are not considerably enough to provide novel and sufficiently robust evidence for the use of W. somnifera in managing DM. To further strength the anti‐diabetic profile of W. somnifera, well‐designed randomized‐controlled trial(s) with a larger sample size and longer duration is warranted with evaluation of its effect primarily on blood glucose, HbA1c and insulin. Future research also needs to elucidate the molecular mechanism(s) of W. somnifera including its active principles in DM.
... There is a plethora of evidence to support the use of several Ayurvedic ingredients, such as Ashwagandha (Withania Somnifera) (6), Brahmi (Bacopa monnieri) (7), Guduchi (Tinospora cordifolia) (8), Shatavari (Asparigus racemosus) (9), Tulsi (10), Curcuma longa, Amalaki (Emblica officinalis) (11) etc in the treatment of T2DM and in preventing its complications. The True Diabetes Reversal Program (TDRP) represents a structured Ayurvedic intervention comprising detoxification therapies and standardized herbal formulations designed to restore metabolic balance and improve glycemic control. ...
... Systematic review and meta-analysis showed that a supplementation with Ashwagandha can improve weight loss, blood glucose and glycosylated haemoglobin, presenting a utility in managing insulin resistance or diabetes. Similarly beneficial results were reported for lipid profile i.e. decrease in total cholesterol and LDLcholesterol [10]. Positive impact of Ashwagandha on total cholesterol and triglycerides was also confirmed [59]. ...
In recent years Withania somnifera (Ashwagandha) gained a lot of interest as an adaptogen, aiding sleep, stress management and presenting health and sports-related benefits. Although clinical effects have been previously reviewed, the specific mechanism of Ashwagandha’s action and its impact on different aspects of physical performance, body composition, as well as medical effects need more thorough analysis. Therefore, this narrative review delves into the available research examining the effects of Ashwagandha supplementation on such qualities as: strength, endurance, power, recovery, muscle mass, body fat, fertility, anxiety, metabolic health and aging, with additional focus on potential mechanisms underlying these effects. Moreover, we propose future perspectives based on the gaps observed in Ashwagandha research up to date.
... Each part of WS varies in the concentration of bioactive compounds and has been tested for toxicity studies as a methanolic or ethanolic extract, seed powder, aqueous alcoholic extract, root paste etc. [10][11][12][13][14][15][16][17][18][19]. Patel et al. [20] investigated the toxicity of methanolic root extract of WS at higher doses viz. ...
Objectives
Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The medicinal properties of WS are ascribed to existence of secondary metabolites which are in great demand in herbal nutraceutical industry. Despite well-known therapeutic effects of WS, it is necessary to assess preclinical toxicity of WS plant on rats and further explore its potential application against treatment of various disorders in humans. The existing study assessed oral acute and sub-chronic toxicities of WS root extract in Sprague Dawley (SD) rats (male and female) for 14 and 90 days, respectively under OECD-423 and -408 guidelines as well as GLP compliance.
Methods
In acute toxicity, rats of either sex were orally fed a dose of 2,000 mg/kg. In sub-chronic toxicity, animals were orally administered repeated doses of WS root extract at 250, 500, 1,000 mg/kg for 90 days with an additional 14-day recovery period. Two more groups (n=5 animals each) receiving vehicle and 1,000 mg/kg of WS root extract for 90 days were also observed.
Results
In acute toxicity, the results revealed that LD50 of WS root extract in SD rats was higher than 2,000 mg/kg. In sub-chronic toxicity, oral administration of extract for 90 days showed no significant toxicological changes in rats. Haematological and serum chemistry markers were found within normal range. Terminal necropsy showed no gross or histopathological outcomes.
Conclusions
The no-observed-adverse-effect level (NOAEL) of WS root extract was 1,000 mg/kg body weight, and safe to use at this dose in rats.
... Each part of WS varies in the concentration of bioactive compounds and has been tested for toxicity studies as a methanolic or ethanolic extract, seed powder, aqueous alcoholic extract, root paste etc. [10][11][12][13][14][15][16][17][18][19]. Patel et al. [20] investigated the toxicity of methanolic root extract of WS at higher doses viz. ...
Objectives
Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The medicinal properties of WS are ascribed to existence of secondary metabolites which are in great demand in herbal nutraceutical industry. Despite well-known therapeutic effects of WS, it is necessary to assess preclinical toxicity of WS plant on rats and further explore its potential application against treatment of various disorders in humans. The existing study assessed oral acute and sub-chronic toxicities of WS root extract in Sprague Dawley (SD) rats (male and female) for 14 and 90 days, respectively under OECD-423 and -408 guidelines as well as GLP compliance.
Methods
In acute toxicity, rats of either sex were orally fed a dose of 2,000 mg/kg. In sub-chronic toxicity, animals were orally administered repeated doses of WS root extract at 250, 500, 1,000 mg/kg for 90 days with an additional 14-day recovery period. Two more groups (n=5 animals each) receiving vehicle and 1,000 mg/kg of WS root extract for 90 days were also observed.
Results
In acute toxicity, the results revealed that LD 50 of WS root extract in SD rats was higher than 2,000 mg/kg. In sub-chronic toxicity, oral administration of extract for 90 days showed no significant toxicological changes in rats. Haematological and serum chemistry markers were found within normal range. Terminal necropsy showed no gross or histopathological outcomes.
Conclusions
The no-observed-adverse-effect level (NOAEL) of WS root extract was 1,000 mg/kg body weight, and safe to use at this dose in rats.
... Kan şekeri seviyelerini düşürebilir Sınırlı sayıdaki kanıtlar, ashwagandhanın diyabet veya yüksek kan şekeri seviyeleri olan kişiler için bazı faydaları olabileceğini göstermektedir. Diyabetli kişilerde yapılan 5 klinik çalışma da dahil olmak üzere 24 çalışmanın incelenmesi, ashwagandha ile tedavinin kan şekerini, hemoglobin A1c'yi (HbA1c), insülini, kan lipitlerini ve oksidatif stres belirteçlerini önemli ölçüde azalttığını buldu (14). Bunun nedeni, ashwagandha içindeki belirli bileşiklerin (withaferin A (WA) adı verilen bir bileşik de dahil) güçlü antidiyabetik aktiviteye sahip olması ve hücrelerin kan dolaşımından glikoz almasını teşvik etmeye yardımcı olabilmesi olabilir (15). ...
Ashwagandha, Hint geleneksel alternatif tıp şekli olan Ayurveda'da en önemli bitkilerinden biridir. Ashwagandha bitkisi, Hindistan ve Güneydoğu Asya'ya özgü sarı çiçekli küçük bir çalıdır. Bu bitkinin kök veya yapraklarından elde edilen ekstreler ve tozu, anksiyete ve kısırlık gibi çeşitli durumları tedavi etmek için kullanmaktadır.
Ashwagandha'nın araştırmalara dayalı 8 potansiyel faydası şunlardır:
• Stres ve anksiyeteyi azaltmaya yardımcı olabilir
• Spor performansına fayda sağlayabilir
• Bazı ruh sağlığı durumlarının belirtilerini azaltabilir
• Erkeklerde testosteronu artırmaya yardımcı olabilir
• Kan şekeri seviyelerini düşürebilir
• İltihabı azaltabilir
• Hafıza dahil olmak üzere beyin fonksiyonlarını iyileştirebilir
• Uykuyu iyileştirmeye yardımcı olabilir
Ashwagandha çoğu insan için güvenli olsa da, herkes için güvenli değildir. Ashwagandha'nın sizin için güvenli olduğundan ve güvenli bir doz kullandığınızdan emin olmak için almadan önce bir sağlık uzmanına danışmanız önemlidir.
... Further, diabetes mellitus (DM) manifests as hyperglycemia and, if untreated, can cause damage to various systems, leading to dysfunction or failure of organs, such as the heart, blood vessels, eyes, kidneys, and nerves [2]. Several traditional medicinal plants are known for their antidiabetic properties, including Terminalia arjuna [3], Commiphora mukul [4], Phyllanthus emblica [5], Azadirachta indica [6], Momordica charantia [7], Berberis asiatica (BA) [8] and Withania somnifera (WS) [9]. These herbal plants have a long history of use in various traditional medicines. ...
Background and aim
Diabetes is a chronic metabolic disorder characterized by elevated blood glucose levels. Although current antidiabetic drugs are highly effective, they are associated with various adverse drug reactions, including life-threatening hypoglycemia, skin rashes, and gastrointestinal intolerance, in addition to being costly. This animal-based experimental study aims to develop a herbal alternative or adjuvant to current antidiabetic drugs using Berberis asiatica (BA) and Withania somnifera (WS), which could potentially have fewer adverse drug reactions and reduce the required dose of existing antidiabetic medications.
Material and methods
Seventy-eight adult albino Wistar rats weighing between 150 and 250 g were used for the study. Diabetes mellitus (DM) was induced by intraperitoneal (i.p) injections of streptozotocin (STZ) (65 mg/kg) 15 minutes after nicotinamide (NIC) (110 mg/kg) administration. As the diabetes was confirmed (blood glucose level > 250 mg/dL), rats were divided into 13 different groups mentioned. The standard antidiabetic drugs (metformin [MET] and glimepiride [GLI]) and polyherbal combinations (PHC) (BA + WS) were administered orally, individually (WS and BA), and in combination (BA + WS). Blood samples were collected for biochemical analysis using the tail vein prick method.
The study is based on a total of 13 groups, six rats in each group. Groups 1 and 2 (normal control [NC] and diabetic control [DC]) received distilled water at a dose of 10 mL/kg orally for 28 days. Groups 3-5 (BA 250, 500, and 1000) received dried ethanolic root extract of BA at a dose of 250, 500, and 1000 mg/kg orally, respectively, for 28 days. Groups 6-8 (WS 250, 500, and 1000) received dried ethanolic root extract of WS at a dose of 250, 500, and 1000 mg/kg orally, respectively, for 28 days. Groups 9-11 (PHC 250, 500, and 1000) received dried ethanolic root extract of BA + WS at a dose of 250, 500, and 1000 mg/kg orally, respectively, for 28 days. Groups 12 and 13 (MET and GLI) received standard drugs MET and GLI at a dose of 250 and 10 mg/kg orally, respectively, for 28 days.
Results
The dried ethanolic root extract of medicinal herbal plants BA and WS and their combination exhibited significant antidiabetic efficacy. PHC has been shown to have a superior antidiabetic effect than individuals. PHC 500 and 1000 showed blood glucose levels similar to those of the GLI group (P < 0.05). Additionally, PHC 1000 showed blood glucose levels similar to those of the MET group (P < 0.05).
Conclusion
Our results indicate that both BA and WS possess hypoglycemic activity, and their combination also has a synergistic antidiabetic effect compared to the individual extract. These findings are promising in developing new safe and cost-effective herbal combinations as alternatives or additives to currently used synthetic antidiabetic drugs.
... They also demonstrated that aqueous extracts of S. lycopersicum inhibit TNF and IL-1 production in LPS-stimulated macrophages. Durg et al. (2020) conducted a systematic review and metaanalysis to determine the efficacy and well-being, and permissibility of Withania somnifera in managing diabetes where they found that it favorably modulated blood sugar, glycosylated hemoglobin, lipid profile, and few oxidative stress biomarkers with concomitantly decreased ill effects. Further, Nabi et al. (2013) described/reported the antihyperglycemic and antihyperlipidemic efficacy of Piper longum in STZ encouraged diabetic rats though they used extracts of roots in their study. ...
... Ashwagandha is used by the ayurvedic practitioners since a long time and reported benefits of it. Different parts of the plant are being used like leaves, root, stem, seeds, fruits, etc. Toxicity studies have been done on different formulations of these parts of the plant like methanolic extract [12], hydroalcoholic extract [13], decoction, seed powder, root paste, etc. [14,15] and it has been found that each part of the plant has got different concentrations of the active ingredient. [16] Balkrishna, A et al. used whole plant extract [17] while Prabu PC et al. tested the acute and sub-acute oral toxicity of hydroalcoholic extract of its roots at 10, 70 and 500 mg/kg doses [18] and Patel SB evaluated the safety of methanol extract of the roots at 500, 1000 and 2000 mg/kg doses. ...
Withania somnifera (ashwagandha, WS) is widely used in traditional Indian Ayurvedic medicine. Studies indicate ashwagandha possesses antioxidant, anxiolytic, memory enhancing, antiparkinsonian, anti-venom, anti-inflammatory and antitumor properties. Present study evaluated the sub-acute toxicity of repeated dose administration of Ashwagandha root extract in wistar rats.
Material and methods
Sub-acute toxicity of Ashwagandha was done as per the OECD-407 guidelines and was carried out for 28 days where satellite group was observed for 43 days. Wistar rats, 30 male and 30 females, were included in the study with 10 [5 M, 5 F] animals per group. Laboratory procedures were performed in accordance with CPCSEA guidelines. Animals were housed in standard laboratory conditions and were administered drugs orally- vehicle to control group and Ashwagandha 200, 400, 800 mg/kg body weight/day to study group. General parameters were noted, blood collection was done for haematological and biochemical parameters. All the animals were sacrificed, dissected and observed for gross necropsy and organs of high dose groups from control and Ashwagandha groups were sent for Histopathological examination.
Result
Gradual weight gain was observed in all the animals. No signs of intoxication and no changes in blood biochemistry were observed. Histopathological changes in organs were within normal limits.
Conclusion
After repeated dose administration, Ashwagandha root powder extract did not show any major abnormality in a dose 5 times of the recommended human dose and above upto 800 mg/kg.
... A systematic review identified ashwagandha as one of the most effective herbal extracts for increasing testosterone concentrations in men (Smith et al., 2021), and in a study on women experiencing perimenopausal symptoms, ashwagandha increased estradiol concentrations and decreased LH concentrations (Gopal et al., 2021). In previous trials, ashwagandha has also altered thyroid hormone concentrations (Sharma et al., 2018), stabilized blood glucose concentrations (Durg et al., 2020), and reduced oxidative stress (Pradhan et al., 2017;Sood et al., 2018). Ashwagandha is also purported to influence HPA axis activity (Lopresti et al., 2022). ...
Background
Stress is a state of homeostasis in the body being challenged, resulting in a systemic response. It has become more prevalent in recent years and affects mental and physical health.
Aims
Evaluate the effects of ashwagandha on stress, fatigue, and sex hormones in overweight or mildly obese men and women with self-reported stress and fatigue.
Methods
Two-arm, parallel-group, 12-week, randomized, double-blind, placebo-controlled trial on overweight or mildly obese men and women aged 40–75 years, supplementing with 200 mg of an ashwagandha root extract (Witholytin®) twice daily.
Results/Outcomes
Supplementation with ashwagandha was associated with a significant reduction in stress levels based on the Perceived Stress Scale (primary outcome); however, the improvements were not significantly different to the placebo group ( p = 0.867). Based on the Chalder Fatigue Scale, there was a statistically significant reduction in fatigue symptoms in the ashwagandha group compared to the placebo group ( p = 0.016), and participants taking ashwagandha also experienced a significant increase in heart rate variability ( p = 0.003). However, there were no significant between-group differences in other self-report outcome measures. In the men taking ashwagandha, there was a significant increase in the blood concentrations of free testosterone ( p = 0.048) and luteinizing hormone ( p = 0.002) compared to the placebo group.
Conclusions/Interpretation
The results of this study suggest that in overweight middle-to-older age adults experiencing high stress and fatigue, compared to the placebo, ashwagandha did not have a significantly greater impact on perceived stress levels. However, based on secondary outcome measures, it may have anti-fatigue effects. This may be via its impact on the autonomic nervous system. However, further research is required to expand on these current findings.
... Phytochemicals derived from Olea europea, Withania somnifera, and Vitis vinifera showed an overall good tolerability and safety profile during clinical use [122,151,[154][155][156][157]159,200,[259][260][261][262][263][264][265][266]. Phytochemicals derived from Camellia sinensis were extensively studied in regard of their pharmacokinetics and safety, and for the clinical use of EGCG, an upper safe-dosage limit (338 mg for extracts; 704 mg for beverages) was recommended [267]. ...
Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by the appearance of painful inflamed nodules, abscesses, and pus-draining sinus tracts in the intertriginous skin of the groins, buttocks, and perianal and axillary regions. Despite its high prevalence of ~0.4–1%, therapeutic options for HS are still limited. Over the past 10 years, it has become clear that HS is a systemic disease, associated with various comorbidities, including metabolic syndrome (MetS) and its sequelae. Accordingly, the life expectancy of HS patients is significantly reduced. MetS, in particular, obesity, can support sustained inflammation and thereby exacerbate skin manifestations and the chronification of HS. However, MetS actually lacks necessary attention in HS therapy, underlining the high medical need for novel therapeutic options. This review directs attention towards the relevance of MetS in HS and evaluates the potential of phytomedical drug candidates to alleviate its components. It starts by describing key facts about HS, the specifics of metabolic alterations in HS patients, and mechanisms by which obesity may exacerbate HS skin alterations. Then, the results from the preclinical studies with phytochemicals on MetS parameters are evaluated and the outcomes of respective randomized controlled clinical trials in healthy people and patients without HS are presented.
... Second, the considerable heterogenicity of the studies regarding outcomes, supplementation dosage, and the length of intervention, did not allow us to conduct a metaanalysis. The great variability in Ws supplementation merits caution when interpreting results; nevertheless, there is robust evidence of the health benefits of Ws in populations with chronic conditions [29,30,51,60]. The variability in the protocols observed in this systematic review warrants future developments on the design of control trials aimed to determine appropriate dose, percentage of withanolides, and duration of Ws supplementation to observe its potential health benefits. ...
Purpose of Review
Withania somnifera (L.) Dunal (Ws) is a common herb plant that has been used for centuries to treat a wide range of conditions, particularly certain chronic diseases due to its antidiabetic, cardioprotective, antistress, and chondroprotective effects, among many others. No conclusive evidence, however, exists about the potential health effects of Ws in adults without chronic conditions. We aimed to evaluate the current evidence on the health benefits of Ws supplementation in healthy adults.
Recent Findings
Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed studies indexed in Web of Science, Scopus, and PubMed to assess the effects of Ws on hematological and biochemical markers, hormonal behavior, and oxidant response in healthy adults. Original articles published up to March 5, 2022, with a controlled trial design or pre-post intervention design, in which supplementation of Ws was compared to a control group or data prior to intervention were included. Among 2,421 records identified in the search, 10 studies met the inclusion criteria. Overall, most of the studies reported beneficial effects of the Ws supplementation, and no serious adverse events were reported. Participants supplemented with Ws displayed reduced levels of oxidative stress and inflammation, and counterbalanced hormone levels. No evidence of the beneficial effects of Ws supplementation on hematological markers was reported.
Summary
Ws supplementation appears to be safe, may regulate hormone levels, and has potent anti-inflammatory and antioxidant effects. However, further studies are needed to elucidate the relevance of its application.
... These ginsenosides are believed to be the primary bioactive compounds responsible for the pharmacological effects of ginseng. [214] [211], [215] Saponin Gensenoside-Ral-3, G-Rbl-2, and G-Rh2 ...
In this day and era disorders like diabetes have become a global incident. A recent survey of World Health Organization (WHO) shows that about 422 million patients are suffering from diabetes, majority population from low income to middle income nations, with around 1.5 million deaths recorded every year worldwide. This number is estimated to rise to 643 million by 2030 and 783 million by 2045. The patients suffering from diabetes are susceptible to other chronic conditions like hypertension, arrhythmia, and low wound healing capabilities. The chemical agents used in treatment of diabetes exhibit a wide range of adverse reactions some of which may be life threatening and affect the quality of life. This requires urgent attention of healthcare practitioners and they should guide their patient through all treatment options including herbal management of the disease rather than expensive modern medicine. This article highlights the major adverse reactions of antidiabetic drugs shedding light on herbal regime to replace these agents.
... Recently, Withaniais used as tea to improve immunity and facilitate detoxification, which helps preserve better health. Ashwagandha roots also reported to not having any toxic effect in studies [10]. ...
Objective: To study the antidiabetic effect of Withania Somnifera root powder (WSR) in Streptozotocin induced diabetic rats. Methods: Diabetes in rats were induced by injecting Streptozotocin intraperitoneally (45 mg/kg of body weight) to overnight fasting rats. Withania Somnifera root was given to group C (100 mg/ kg of body weight) and Pioglitazone to group D (20 mg/kg of body weight) orally for 4 weeks respectively. Blood glucose level, glycated Hb, insulin, protein tyrosine kinase activity and serum DPP-4 levels were measured. Results: Significant Improvement in body weight, glycemic profile, dyslipidemia and tyrosine kinase activity were observed in WSR treated rats at week 4 of the study compared to diabetic control rats. Blood glucose level, glycated Hb and Serum DPP4 levels, were also found to be decreased in WSR treated rats compared to diabetic control rats at the end of study. This is possibly due to augmented serum insulin levels and increased insulin sensitivity after treatment with WSR. Conclusion: The results from above study it was concluded that Withania Somnifera root powder has antidiabetic activity. Further study required to confirm the exact mechanism of action.
... In general, the clinical use of phytochemicals derived from Withania somnifera was found to be tolerable and safe, indicated by pharmacokinetics and safety data obtained from clinical trials [97][98][99][100][101][102][103]. The clinical use of Camellia sinensis-derived phytochemicals was extensively studied in clinical trials and respective pharmacokinetic and safety data are available [104]. ...
Hidradenitis suppurativa (HS; also designated as acne inversa) is a chronic inflammatory disease characterized by painful skin lesions that occur in the axillary, inguinal, gluteal and perianal areas of the body. These lesions contain recurring deep-seated, inflamed nodules and pus-discharging abscesses and fistulas. Affecting about 1% of the population, this common disease has gained appropriate clinical attention in the last years. Associated with numerous comorbidities including metabolic syndrome, HS is considered a systemic disease that severely impairs the quality of life and shortens life expectancy. Therapeutic options for HS are limited, comprising long-term antibiotic treatment, the surgical removal of affected skin areas, and neutralization of TNF-α, the only approved systemic treatment. Novel treatment options are needed to close the therapeutic gap. HS pathogenesis is increasingly better understood. In fact, neutrophilic granulocytes (neutrophils) seem to be decisive for the development of the purulent destructive skin inflammation in HS. Recent findings suggest a key role of the immune mediators IL-1β, IL-17A and G-CSF in the migration into and activation of neutrophils in the skin. Although phytomedical drugs display potent immunoregulatory properties and have been suggested as complementary therapy in several chronic disorders, their application in HS has not been considered so far. In this review, we describe the IL-1/IL-17/G-CSF axis and evaluate it as potential target for an integrated phytomedical treatment of HS.
... The destructive effect of DM on β-cells of the islet of Langerhans causes liberation of nitric oxide (NO) with inhibition of aconitase enzyme activity, both causing more destruction of the pancreatic β-cells with subsequent inhibition of insulin secretion, hyperglycemia and decreased uptake of glucose by skeletal muscles, liver and adipose tissue. Moreover, the disturbed carbohydrate metabolism could lead to excess glucose in the blood, which in-turn will react with hemoglobin irreversibly, and so increases the levels of HbA1c% [41] . ...
... Withania somnifera (Ashawagandha), also called "Indian ginseng", is an herb highly valued and used for centuries by Ayurvedic medicine, mainly for its adaptogenic and antistress activity, which is considered a proven Rasavātam [119] Due to its safety and effectiveness in improving quality of life and physical performance while decreasing fatigability [120], Ashwagandha is one of the most studied herbal products with potential antimicrobial, anti-inflammatory, antitumor, antistress, neuroprotective, cardioprotective, antioxidant, and antidiabetic properties [121][122][123]. ...
Sarcopenia, an age-related decline in skeletal muscle mass and function, dramatically affects the quality of life. Although there is a consensus that sarcopenia is a multifactorial syndrome, the etiology and underlying mechanisms are not yet delineated. Moreover, research about nutritional interventions to prevent the development of sarcopenia is mainly focused on the amount and quality of protein intake. The impact of several nutrition strategies that consider timing of food intake, anti-inflammatory nutrients, metabolic control, and the role of mitochondrial function on the progression of sarcopenia is not fully understood. This narrative review summarizes the metabolic background of this phenomenon and proposes an integral nutritional approach (including dietary supplements such as creatine monohydrate) to target potential molecular pathways that may affect reduce or ameliorate the adverse effects of sarcopenia. Lastly, miRNAs, in particular those produced by skeletal muscle (MyomiR), might represent a valid tool to evaluate sarcopenia progression as a potential rapid and early biomarker for diagnosis and characterization.
... WS, being a Rasayana botanical, shows immune homeostasis through cytokine modulation (Rasool and Varalakshmi, 2006), anti-inflammatory (Ritchie and Singanayagam, 2020), and organprotective effects. There is well-explored scientific evidence of clinical benefits of WS in diabetes (Durg et al., 2020), hypertension (Shalini Kushwaha et al., 2012c), and cancer (Biswal et al., 2013). Therefore, the Rasayana effect of WS may be beneficial in the multifactorial pathophysiology of COVID-19. ...
As the COVID-19 pandemic is progressing, the therapeutic gaps in conventional management have highlighted the need for the integration of traditional knowledge systems with modern medicine. Ayurvedic medicines, especially Ashwagandha (Withania somnifera (L.) Dunal, WS), may be beneficial in the management of COVID-19. WS is a widely prescribed Ayurvedic botanical known as an immunomodulatory, antiviral, anti-inflammatory, and adaptogenic agent. The chemical profile and pharmacological activities of WS have been extensively reported. Several clinical studies have reported its safety for use in humans. This review presents a research synthesis of in silico, in vitro, in vivo, and clinical studies on Withania somnifera (L.) Dunal (WS) and discusses its potential for prophylaxis and management of COVID-19. We have collated the data from studies on WS that focused on viral infections (HIV, HSV, H1N1 influenza, etc.) and noncommunicable diseases (hypertension, diabetes, cancer, etc.). The experimental literature indicates that WS has the potential for 1) maintaining immune homeostasis, 2) regulating inflammation, 3) suppressing pro-inflammatory cytokines, 4) organ protection (nervous system, heart, lung, liver, and kidney), and 5) anti-stress, antihypertensive, and antidiabetic activities. Using these trends, the review presents a triangulation of Ayurveda wisdom, pharmacological properties, and COVID-19 pathophysiology ranging from viral entry to end-stage acute respiratory distress syndrome (ARDS). The review proposes WS as a potential therapeutic adjuvant for various stages of COVID-19 management. WS may also have beneficial effects on comorbidities associated with the COVID-19. However, systematic studies are needed to realize the potential of WS for improving clinical outcome of patients with COVID-19.
... The biologically active compound withaferin A is one of the important pharmacologically active compounds used in the different medicinal treatments in the last few decades (Behl et al., 2020;Dutta et al., 2019). Withaferin A is effectively used for the treatment of different types of cancer and cancer cells (Behl et al., 2020;Sivasankarapillai et al., 2020;Hahm et al., 2013) as well as for the other medicinal treatments like frontotemporal dementia, diabetes mellitus, cognitive dysfunction, etc. (Borchelt, 2021;Durg et al., 2020;Ng et al., 2020). Withaferin A is an agent of withanolides group. ...
Physalis minima L. is commonly known as wild Gooseberry. Traditionally this plant has been used in different ethnopharmacological and modern medicinal practices. No systematic evaluation is done from an underutilized alternative resource of withaferin A content from P. minima. Withaferin A is a steroidal lactone withanolide mainly found in the plant Withania somnifera and other few members of family Solanaceae. The present investigation evaluated withaferin A content from 30 chemotypes collected from different geographical regions in India. Among 30 different chemotypes, an elite clone (17.13 ± 0.31 mg/g dry weight (DW) withaferin A) was selected for in vitro shoot multiplication. Well-organized micropropagation has been studied using five different cytokinins in Murashige and Skoog (MS) medium. Among them, aromatic cytokinin “meta-Topolin” (mT) at 1.0 mg/l triggered the highest number (83.26 ± 1.02) of multiple shoots and shoot length (4.87 ± 0.69) after 28 days of explant implantation. Maximum root induction was showed in ½ MS medium with 0.5 mg/l indole-3-butyric acid (IBA) to trigger 75.65 ± 1.03 roots and root length 4.56 ±0.25 cm after 14 days of culture. In vitro well-rooted plantlets were excised for hardening and show; 99.02% survival rate. Genetic stability of micropropagated plants were performed with cytological and molecular marker-based selection. Simultaneously, phytochemical stability was performed with HPLC (High performance liquid chromatography) analysis. In our experiment no significant difference showed between the mother plant and micropropagated plants. Thus, our protocol can be used for large-scale commercial cultivation of elite chemotype of this medicinal plant.
... Based on the results of four studies there is preliminary evidence to suggest ashwagandha may reduce blood glucose concentrations, improve endothelial function, reduce oxidative stress and inflammatory markers, and improve diabetes-related distress in adults with diabetes. In a recently published systematic review and meta-analysis based on the results of six in-vitro, 13 pre-clinical, and five clinical studies, it was concluded that ashwagandha altered concentrations of blood glucose, glycosylated haemoglobin, insulin, blood lipids, and serum and oxidative stress markers in adults with diabetes mellitis; however, the overall clinical evidence was limited and more robustly-designed studies are required (Durg et al., 2020). Conclusions about the effects of ashwagandha on other health and performance parameters cannot be made due to the limited number of studies conducted to date. ...
Ashwagandha is a medicinal plant that has been used in Ayurvedic and indigenous medicine for over 3,000 years. Because interest and the popularity of ashwagandha has increased in several Western countries, there are an increasing number of human trials evaluating its efficacy across a range of conditions. Based on the PRISMA guidelines, human trials assessing the effects of ashwagandha on mental and/or physical conditions, and/or human performance, used as a stand-alone or adjunct intervention, and delivered as a single ingredient, were eligible for inclusion in this systematic review. Forty-one studies were identified examining the effects of ashwagandha on stress and anxiety, sexual function and fertility, athletic performance, cognitive performance, pain, fatigue, thyroid function, schizophrenia, diabetes, obsessive-compulsive disorder, insomnia, hypercholesterolemia, and tuberculosis. Results from most of these studies indicated positive effects from ashwagandha intake, although treatment dose, duration, and extract types varied significantly. Moreover, trials often comprised of small sample sizes and were primarily conducted in India (32 studies). Overall, the strongest evidence for therapeutic efficacy of ashwagandha is the alleviation of stress and anxiety symptoms. The results from this systematic review suggest ashwagandha has a potentially large array of therapeutic applications. However, while promising, the significant heterogeneity across studies and the limited number of investigations means further research utilising robust and adequately-powered study designs are required.
... Although it has been used therapeutically for a number of reasons, Ashwagandha supplementation lacks sufficient information to be considered effective for all proposed conditions [4]. However, several recent systematic reviews and meta-analyses have shown its potential and safety for controlling anxiety [12], fighting male infertility [13], improving the function of the reproductive system [14], serving as an adjuvant to the treatment of diabetes [15] and avoiding the deterioration of cognitive function [16]. However, it seems that some of the secondary metabolites of Ashwagandha could have some potential at the level of physical performance improvement, being responsible for various effects at the metabolic and physiological level through the regulation of certain anti-inflammatory and anti-oxidative pathways [4,17]. ...
Ashwagandha (Withania somnifera) is considered a potent adaptogen and anti-stress agent that could have some potential to improve physical performance. This preferred reporting items for systematic reviews and meta-analyses (PRISMA)-based comprehensive systematic review and Bayesian meta-analysis aimed to evaluate clinical trials up to 2020 from PubMed, ScienceDirect, and Google Scholar databases regarding the effect of Ashwagandha supplementation on physical performance in healthy individuals. Besides implementing estimation statistics analysis, we developed Bayesian hierarchical models for a pre-specified subgroup meta-analysis on strength/power, cardiorespiratory fitness and fatigue/recovery variables. A total of 13 studies met the requirements of this systematic review, although only 12 were included in the quantitative analysis. A low-to-moderate overall risk of bias of the trials included in this study was detected. All Bayesian hierarchical models converged to a target distribution (Ȓ = 1) for both meta-analytic effect size (μ) and between-study standard deviation (τ). The meta-analytic approaches of the included studies revealed that Ashwagandha supplementation was more efficacious than placebo for improving variables related to physical performance in healthy men and female. In fact, the Bayesian models showed that future interventions might be at least in some way beneficial on the analyzed outcomes considering the 95% credible intervals for the meta-analytic effect size. Several practical applications and future directions are discussed, although more comparable studies are needed in exercise training, and athletic populations are needed to derive a more stable estimate of the true underlying effect.
... In another meta-analysis of randomized controlled clinical trials, Momordica charantia L. fruit extract was shown to significantly alleviate diabetes mellitus among individuals with type 2 diabetes mellitus (Peter et al., 2019). Also, Withania somnifera significantly restored the elevated levels of blood glucose, glycosylated haemoglobin (HbA1c), insulin, and lipid profile (Durg et al., 2020). On the other hand, Syzygium cumini tea prepared from leaves of S. cumini had no antidiabetic effect (Teixeira et al., 2006). ...
Abstract
Ethnopharmacological relevance
The increasing national prevalence of diabetes mellitus (DM) and its complications have overstretched the health care system in Tanzania and influenced patients to use herbal medicines as alternative therapeutic strategies. Therefore, an urgent need exists to validate the safety and efficacy of plants used locally.
Aim of the study
To identify plants used for the management of DM in Tanzania and analyses their pharmacological, phytochemistry, and safety evidence with a special focus on the mechanism of action.
Methods
Researchers searched Medline, web of science, and Scopus for published articles. Also, specialized herbarium documents of Muhimbili Institute of traditional medicine were reviewed. Articles were assessed for relevance, quality, and taxonomical accuracy before being critically reviewed.
Results
We identified 62 plant species used locally for DM management. Moringa oleifera Lam. and Cymbopogon citratus (D.C) stapf were the most mentioned. Fifty-four phytochemicals from 13 species had DM activities. These were mainly; polyphenolics, phytosterols, and triterpenoids. Extracts, fractions, and pure compounds from 18 species had in vitro antidiabetic activities of which 14 had α-glucosidase and α-amylase inhibition effects. The most studied -Momordica charantia L. increased; glucose uptake and adiponectin release in 3T3-L1 adipocytes, insulin secretion, insulin receptor substrate-1 (IRS-1), GLUT-4 translocation, and GLP-1 secretion; and inhibited protein tyrosine phosphatase 1 B (PTP1B). Preclinical studies reported 30 species that lower plasma glucose with molecular targets in the liver, skeletal muscles, adipose tissues, pancreases, and stomach. While three species; Aspilia mossambiscensis (Oliv.) Willd, Caesalpinia bonduc (L.) Roxb, and Phyllanthus amarus Schumach. & Thonn. had mild toxicity in animals, 33 had no report of their efficacy in DM management or toxicity.
Conclusion
Local communities in Tanzania use herbal medicine for the management of DM. However, only a fraction of such species has scientific evidence. A. mossambiscensis, C. bonduc., and P. amarus had mild toxicity in animals. Together, our findings call for future researches to focus on in vitro, in vivo, and phytochemical investigation of plant species for which their use in DM among the local communities in Tanzania have not been validated.
... Furthermore, well-designed randomized controlled trials (RCTs) with a larger sample size and longer duration are warranted to evaluate its effect primarily on blood glucose, HbA1c, and insulin. 386 In five studies conducted in patients with anxiety and stress, significant (in most cases) improvements were observed with Withania intervention as compared with placebo, but cases of potential bias were identified. 383 There is some evidence from randomized, placebo-controlled, double-blind trials regarding the benefits of W. somnifera on cognitive function, such as improved performance on cognitive tasks, attention, and reaction time. ...
Adaptogens comprise a category of herbal medicinal and nutritional products promoting adaptability, resilience, and survival of living organisms in stress. The aim of this review was to summarize the growing knowledge about common adaptogenic plants used in various traditional medical systems (TMS) and conventional medicine and to provide a modern rationale for their use in the treatment of stress-induced and aging-related disorders. Adapto-gens have pharmacologically pleiotropic effects on the neuroendocrine-immune system, which explain their traditional use for the treatment of a wide range of conditions. They exhibit a biphasic dose-effect response: at low doses they function as mild stress-mimetics, which activate the adaptive stress-response signaling pathways to cope with severe stress. That is in line with their traditional use for preventing premature aging and to maintain good health and vitality. However, the potential Med Res Rev. 2020;1-74. wileyonlinelibrary.com/journal/med | 1 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Type 1 diabetes (T1DM) is one of the most common chronic metabolic diseases in the world. Insulin replacement therapy and drug adjuvant therapy are the main means of modern medical treatment of T1DM; still, there are adverse reactions such as drug resistance, which seriously hinder the therapeutic effect. As a unique medical method in China, traditional Chinese medicine (TCM) has a significant effect on the treatment of T1DM. TCM therapy can reduce the symptoms of T1DM, prevent complications, improve insulin resistance, and promote insulin secretion. In recent years, the research field of TCM in the treatment of T1DM has made considerable progress. The research on the treatment of T1DM by Chinese herbal medicine, TCM prescription, acupuncture, and moxibustion shows good anti‐T1DM effect and significantly improves the survival rate of patients. This article aims to summarize the methods of TCM in the treatment of T1DM, expounds on the mechanism of action in the treatment of T1DM, and discusses the limitations and opportunities of TCM in the treatment of T1DM.
Background: Research on diabetes treatment is advancing yearly, and it is estimated that 643 million adults worldwide will have diabetes by 2030. This is a comprehensive review of antidiabetic mechanisms in medicinal plants, aims to identify natural antidiabetic plants and provide details on their mechanisms of action, and rigorous testing techniques. Methodology: Information was gathered from offline and online sources to identify indigenous medicinal plants that lower blood glucose. Different databases were searched for ethnopharmacological literature using the following keywords: medicinal plants, diabetes, and India. Other sections about clinical trials, toxicological evaluations of certain plants, and preclinical trials have since been added. These sections were retrieved from Scopus using pertinent keywords. In this study, 117 species of medicinal plants from 55 families that are used to treat diabetes mellitus were listed. Conclusion: The variety of plants discussed in this review clearly demonstrated the importance of herbal plants in the treatment of diabetes. Result of the study shows Fabaceae, Rutaceae, and Combretaceae were the most prevalent plant families and species having antidiabetic properties among these plants. It also gives researchers information that they may use to develop future plans, like finding plants that may be effective in preventing diabetes and isolating bioactive molecules to help manage the disease. More research is necessary to completely comprehend these newly identified anti-diabetic drugs at the molecular, therapeutic, and physiological levels, nevertheless, in order to treat and manage diabetes mellitus globally
Withania somnifera, commonly known as Ashwaganda, is an important medicinal plant for a long time. Roots, seeds and other parts of Ashwaganda have clinically important pharmacological properties. The phytochemicals present in the plant include flavonoids, alkaloids, phenols and withanolids which make it useful in treatment of cancer, cardiovascular diseases and diabetes. Withania somnifera possess anti-inflammatory, anticancer, antioxidant, antimicrobial and anti-aging activities. Nanobiotechnology is an emerging field as nanoparticles allow targeted and controlled drug delivery. Green synthesis of nanoparticles involves the use of plants for their ability to reduce harmful impacts associated with chemically synthesized nanoparticles. The green synthesis approach has been applied for the synthesis of nanoparticles form plant extracts obtained from Withania somnifera. Silver, gold, selenium, platinum and many more nanoparticles have been synthesized by mixing the root extracts of Ashwaganda and metal salts. Another approach involves the use of plant extracts encapsulated in niosomes and in combination with solid lipid nanoparticles which is pharmacologically helpful. The nanoparticles from Withania somnifera utilize anti-inflammatory, anticancer, antioxidant, antimicrobial and anti-aging activities of Ashwaganda and help in targeted delivery of the drug. The plant-based nanoparticles show better characteristics including bioavailability, solubility and improved shelf life. This approach can be developed further for agricultural and technological uses like sensors and imaging technology.
Diabetes mellitus is a chronic metabolic disorder which is commonly found life-threatening disease and it continuously reducing the life expectancy. It is characterized by hyperglycaemia (raised blood sugar level) resulting from defects in insulin secretion, action, or both. Since thousands of years, medicinal plants are being used by our ancestors for the prevention, treatment or even cure the diabetes mellitus. Utilization of these herbal plants is increasing rapidly last two to three decades due to their lesser toxicity and cost effectiveness property as compared to synthetic drugs. In this review, approximately 30 medicinal plants were described which are native to India and traditionally used by the people living in shivalik range of Himalaya in Uttarakhand (specially Dehradun & Haridwar) for the treatment of diabetes mellitus. The data about these plants was collected from science direct, PubMed, web of science, scopus, mdpi, google scholar and different other search engines and websites. This review was conferred in a systematic way as it includes botanical name, family, vernacular name, parts used and pharmacological uses of plants in a tabulated form. There are various scientific evidences behind the uses of some medicinal plants which have been mentioned along with the summary of individual medicinal plant. In this review, all the plants and herbs are easily available in these regions of Uttarakhand and local people traditionally uses these plants as vegetable, seasoning, flavouring and usually consume as a part of their diet. There are some limitations of phytotherapy which limit it to completely replace the allopathic therapy as less bioavailability, less rate of absorption and slow rate of dissolution. But by using various advanced dosage forms (phytosomes, neosomes, liposomes, nanoparticles, nanobubbles, nano diamonds, nanosphere etc.) and method of delivery (various invasive and non-invasive methods) which can bypass these all problems associated with the potency and efficacy of phytochemicals.
Psychosis is a state of mind that makes it difficult to determine what is real and what is not. Psychosis can have serious negative effects. Like many psychiatric phenomena, psychosis has a variety of causes, such as schizophrenia, bipolar disorder, and psychotic depression. Antipsychotic medications, psychotherapy, and social support are the most common treatments. Antipsychotic drugs reduce the symptoms of psychosis by changing brain chemistry. Based on the mechanism of action, antipsychotics have two groups, typical and atypical. Most people who take antipsychotics experience side effects. People taking typical antipsychotics tend to have higher rates of extrapyramidal side effects, but some atypical drugs, especially olanzapine, are associated with the risk of significant weight gain, diabetes, and metabolic syndrome, which, in turn, increases the risk of atherosclerotic cardiovascular disease and premature death. Physical exercise, diet regimen, psychoeducation, monotherapy, or switching to an alternative antipsychotic are strategies to correct metabolic aberrates in atypical antipsychotic users. In light of several successful studies on the use of medicinal plants to control metabolic syndrome, this article briefly reviews the studies on some herbal medications for the management of metabolic disorders associated with atypical antipsychotics and discusses probable mechanisms. Therefore, we searched the Cochrane, Scopus, PubMed, and Google Scholar databases for works published before July, 2022, on the effect of herbal medications on antipsychotic-related metabolic abnormalities in animals or humans. We recommend that some herbal medicines may be efficient for regulating the metabolic changes related to atypical antipsychotics due to their multipotential action, and more efforts should be made to make herbal drug treatments more effective. We hope this review will be a reference for research on developing herbal therapeutics for metabolic alterations in antipsychotic customers.
Background
Diabetes is prevalent globally; India stands amongst the first two countries with the highest percentage of adults aged 20–79 years with diabetes in 2021. Anti-diabetic agents and insulin offer profound side effects. Phytoconstituents regulate blood sugar, improve health status and reduce dependency on anti-diabetic medications. This research aims to generate clinical evidence of Diabetic Support Product (GP/PROD/2021/001) in the treatment of type 2 diabetes.Trial designA randomized, double-blind, placebo-controlled clinical trial was conducted on 150 individuals with type 2 diabetes mellitus. Subjects were divided into two parallel groups and given either GP/PROD/2021/001 or a placebo tablet; 2 tablets twice a day after meals for 90 days.Methods
Interventions were adjuvant to the standard medication. The research objectives were to evaluate changes in fasting and post-meal plasma glucose and HbA1c in patients with type 2 diabetes.ResultsIn 90 days, GP/PROD/2021/001 group showed a substantial improvement in all key biochemical markers-HbA1c, FBS, and PPBS when compared to the placebo group. A reduced HOMA-IR score suggests reduced insulin resistance. Quality of life improved in GP/PROD/2021/001 group than placebo. On day 90, there was a significant decrease in HbA1c levels in GP/PROD/2021/001 (23.51%) group than placebo (6.21%). The test group reduced their dependency on conventional antidiabetic medication and insulin.Conclusion
It can be concluded from the study that the advanced diabetic support formula (GP/PROD/2021/001) is a safer and more effective option as an adjuvant in the management of diabetes from newly diagnosed to chronic diabetic patients.Trial registrationCTRI/2022/01/039179 [Registered on: 05/01/2022] Trial Registered Prospectively.
Most alternative treatments are to be taken by mouth; less often they must be applied externally as creams. These modalities include, for instance, dietary supplements, homeopathic remedies, or herbal medicines. In this chapter, I discuss prominent examples from these categories. As there are many more, I focus on those that are best-known.
Ageing is an innate indispensable physiological process largely conceived as general decline in body functions and defense mechanisms. While ageing per se is not a disease, there are many age-related pathologies, modulation of which is considered as anti-ageing in several ways. Chronic stress often triggers senescence-inducing mechanisms manifested as premature/rapid ageing. The latter is associated with a high incidence of stress-related disorders such as cancer, neurodegeneration, metabolic disorders and muscle/bone dysfunctions. Cell culture system provides an easy and convenient experimental system to study mechanisms of natural (replicative) and stress-induced ageing. We, over the years, have researched molecular mechanisms of ageing and age-related pathologies, and their modulation with natural compounds using cell culture as a model system. Among several others, bioactives from Ashwagandha (Withania somnifera) have emerged as useful natural compounds with a variety of activities and are hence predicted to assist in health care in stress and disease states. In this chapter, we describe highlights of our research work demonstrating the therapeutic potential of Ashwagandha leaves that offer advantage over roots in terms of availability, processing and being enriched with active compounds.
Introduction- Many environmental risk factors are associated with some form of chronic inflammation. The spread of COVID-19 across the world has impacted every one of us. The first case of coronavirus was reported on 30 January 2020 in India originating from China.
Study Area- India has a tremendous capacity to deal with the coronavirus outbreak because of its high immunity and climatic conditions. Maintaining social distancing and hand washing is not a sufficient step for preventing COVID-19. Indian system of traditional medicine has a potential worth to enhance immunity, which can resist a novel coronavirus.
Material & Methods- A detailed study was carried out by analyzing national and international scientific databases (PubMed, SciFinder, ScienceDirect, Scopus, and Web of Science, Mendeley), thesis, and recognized books. Only Indian herbs with high immunity resistant power were analyzed. Epidemiologic studies with information on COVID-19 risk factors and precautions also considered for study purposes.
Results- Some herbs like Ocimum tenuiflorum (Tulsi), Glycyrrhiza glabra (Liquorice), Curcuma domestica Vahl (Turmeric), Tinospora cordifolia (Giloy), Withania somnifera (Ashwagandha), Cinnamon (Dalchini), Shoot of Triticumaestivum Linn. (Wheatgrass), Andrographis paniculata (Kalmegh), can help in boosting immunity for COVID-19 disease.
Discussion- Despite the shreds of evidence for the efficacy of these herbs in treating coronavirus induced infections; the proper dose with ideal timing for such interventions needs to verify in clinical trials. Researchers must have to take the privilege to explore the potential of herbs to reduce such epidemics of environmental threats.
Ashwagandha (Withania somnifera) is a herb commonly used in Ayurvedic medicine to promote youthful vigor, enhance muscle strength and endurance, and improve overall health. In this 16-week, randomized, double-blind, placebo-controlled, crossover study, its effects on fatigue, vigor, and steroid hormones in aging men were investigated. Overweight men aged 40–70 years, with mild fatigue, were given a placebo or an ashwagandha extract (Shoden beads, delivering 21 mg of withanolide glycosides a day) for 8 weeks. Outcome measures included the Profile of Mood States, Short Form (POMS-SF), Aging Males’ Symptoms (AMS) questionnaire, and salivary levels of DHEA-S, testosterone, cortisol, and estradiol. Fifty-seven participants were enrolled, with 50 people completing the first 8-week period of the trial and 43 completing all 16 weeks. Improvements in fatigue, vigor, and sexual and psychological well-being were reported over time, with no statistically significant between-group differences. Ashwagandha intake was associated with an 18% greater increase in DHEA-S (p = .005) and 14.7% greater increase in testosterone (p = .010) compared to the placebo. There were no significant between-group differences in cortisol and estradiol. In conclusion, the intake of a standardized ashwagandha extract (Shoden beads) for 8 weeks was associated with increased levels of DHEA-S and testosterone, although no significant between-group differences were found in cortisol, estradiol, fatigue, vigor, or sexual well-being. Further studies with larger sample sizes are required to substantiate the current findings.
Objective: To find out whether an isolated compound (IC) from the ethanolic extract of roots of ashwagandha prevents stress-induced hyperglycemia by direct interference with the action of increased concentration of corticosterone on hepatocytes or by preventing hyper-secretion of corticosterone or both.Methods: A group of rats served as controls, and those in another group were subjected to restraint (1 h) and forced swimming exercise (15 min), after a gap of 4 h daily for 4 w. The third group of rats received orally IC (5 mg/kg bw/rat) 1 h prior to exposure to stressors. After the last treatment period, a blood sample was collected and serum was separated for the estimation of corticosterone and glucose. In in vitro experiment, hepatocytes were treated with different concentrations of corticosterone (100, 200, 300, 400 and 500 ng/ml). In another set of experiment, hepatocytes were treated with different doses of IC (1, 10, 100, 1000 and 10 000 μg/ml of medium) along with corticosterone (400ng/ml). The concentration of glucose and activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were determined after the treatment.Results: Stress exposure caused a significant increase in serum concentration of corticosterone and glucose whereas, administration of IC did not result in similar changes. Further, treatment of corticosterone in in vitro significantly increased the activities of PEPCK and G6Pase and concentration of glucose in a dose-dependent manner in hepatocytes. However, treatment with IC did not interfere with the corticosterone-induced an increase in the activities of PEPCK and G6Pase as well as the concentration of glucose in hepatocytes.Conclusion: The in vivo and in vitro results put together reveal that IC does not directly interfere with the action of corticosterone on hepatocytes. However, it prevents stress-induced hyperglycemia by suppressing hyper-secretion of corticosterone.
Abstract Background This study was to explore the effect of hyperlipidemia on the incidence of cardio-cerebrovascular diseases in patients with type 2 diabetes. Methods Three hundred ninety five patients with type 2 diabetes in our hospital from January 2012 to January 2016 were followed up with an average of 3.8 years. The incidence of cardio-cerebrovascular diseases between diabetes combined with hyperlipidemia group (195 patients) and diabetes group (200 patients) were made a comparison. Multivariable Cox’s proportional hazards regression model was used to analyze the effect of hyperlipidemia on the incidence of cardio-cerebrovascular diseases in patients with type 2 diabetes. Results Diastolic blood pressure, systolic blood pressure, high-density lipoprotein, low-density lipoprotein, body mass index and hyper-sensitive C-reactive protein were higher in diabetes combined with hyperlipidemia group than in diabetes group (P
The present investigation explores the possibilities of using the root and leaf extracts of
an important plant Withania somnifera targeting DM and to examine their hypoglycaemic and
hypolipidaemic effects on Streptozotocin-induced diabetic rats.Withania somnifera root extracts
(WSREt) and leaf extracts (WSLEt) were orally administered daily to diabetic rats for eight
weeks. After the treatment period, blood glucose and serumenzymes like aspartate transaminase
(AST), alanine transaminase (ALT) and alkaline phosphatase (ALP), total cholesterol,
triglycerides, HDL-c high density lipoprotein-bound cholesterol, LDL-c low density lipoproteinbound
cholesterol l, LDHand serum proteins levelswere determined. The levels of blood glucose,
AST, ALT, ALP, LDH, serum lipids except high density lipoprotein-bound cholesterol (HDL-c)
were significantly increased, but total protein albumin, albumin : globulin (A : G) ratio, were
significantly decreased in streptozotocin-induced diabetic rats. Treatment of the diabetic rats
with root and leaf extracts altered the changes of the above parameters and restored them after
eight weeks of treatment, indicating that the extracts possess hypoglycaemic and hypolipidaemic
properties, hence useful in diabetes mellitus.
Aging is now at the forefront of major challenges faced globally, creating an immediate need for safe, widescale interventions to reduce the burden of chronic disease and extend human healthspan. Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications. However, each faces issues with approval for off-label, prophylactic use due to adverse effects. Here, we initiate an effort to identify nutraceuticals-safer, naturally-occurring compounds-that mimic the anti-aging effects of metformin and rapamycin without adverse effects. We applied several bioinformatic approaches and deep learning methods to the Library of Integrated Network-based Cellular Signatures (LINCS) dataset to map the gene- and pathway-level signatures of metformin and rapamycin and screen for matches among over 800 natural compounds. We then predicted the safety of each compound with an ensemble of deep neural network classifiers. The analysis revealed many novel candidate metformin and rapamycin mimetics, including allantoin and ginsenoside (metformin), epigallocatechin gallate and isoliquiritigenin (rapamycin), and withaferin A (both). Four relatively unexplored compounds also scored well with rapamycin. This work revealed promising candidates for future experimental validation while demonstrating the applications of powerful screening methods for this and similar endeavors.
Purpose: The present study was intended to investigate the preventive role ofWithania somnifera (WS) on hyperlipidemia and oxidative stress in the heart of streptozotocin (STZ)-induced type 2 diabetic rats. Methods: Single intraperitoneal injection of STZ (100 mg/kg) was given to 2 days rat pups to induce type 2 diabetes mellitus. Diabetes was confirmed 90 days after the administration of STZ by measuring blood glucose level. WS (200 and 400 mg/kg) was administered orally once a day for 5 weeks after the confirmation of diabetes. Glucose, lactate dehydrogenase (LDH), creatinine kinase (CK), total cholesterol (TCh), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), verylow density lipoprotein cholesterol (VLDL-C) and markers of oxidative stress parameters like lipid peroxidation (LPO), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) were evaluated in the heart of type 2 diabetic rats. Results: Oral administration of WS for 5 weeks resulted in a significant (P<0.001) reduction in glucose, LDH, CK, TC, TG, LDL-C, VLDL-C levels with significant elevation of HDL-C levels. On the other hand, WS treated diabetic rats significantly (P<0.01-P<0.001) reduced the elevated levels of LPO, increased levels of antioxidant enzymes (i.e, GSH, GPx, GR, GST, SOD and CAT). Conclusion: These findings propose the role of hyperlipidemia and cardiac oxidative stress in type 2 diabetic rats and suggested protective effect of WS in this animal model. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved.
Antidiabetic potential of leaf and root extracts of
Withania somnifera from Nimuch, Lucknow, Mumbai and Karnataka
regions of India were evaluated against 3T3F442A fibroblast (3T3
adipocyte) cell line using glucose uptake assay. Leaf extracts from all
the four regions were active on the cell line tested. Samples from
Mumbai region found to be more active when compared with other
regions. Root extracts also gave good glucose promoting activity in
the presence of insulin. Nimuch samples were mere active than
Mumbai samples. Isolated fractions and standard Withaferin-A and
Withanolide-A were active at 20 μg/ml. This concentration was higher
than that for crude leaf extract from Mumbai region and crude extracts
from Nimuch region. Crude extract of Withania somnifera have good
antidiabetic potential indicating the synergistic effect of these extract
on glucose uptake of 3T3 fibroblast in presence of insulin.
Diabetes is a global endemic with rapidly increasing prevalence in both developing and developed countries. The American Diabetes Association has recommended glycated hemoglobin (HbA1c) as a possible substitute to fasting blood glucose for diagnosis of diabetes. HbA1c is an important indicator of long-term glycemic control with the ability to reflect the cumulative glycemic history of the preceding two to three months. HbA1c not only provides a reliable measure of chronic hyperglycemia but also correlates well with the risk of long-term diabetes complications. Elevated HbA1c has also been regarded as an independent risk factor for coronary heart disease and stroke in subjects with or without diabetes. The valuable information provided by a single HbA1c test has rendered it as a reliable biomarker for the diagnosis and prognosis of diabetes. This review highlights the role of HbA1c in diagnosis and prognosis of diabetes patients.
Background: The use of Withania somnifera is increasing due to a number of its chemical constituents found useful for health.
Objective: The present study was carried out to investigate the potential adverse effects (if any) of a standardized Withania somnifera extract (WSE) in rats following acute and sub chronic administration.
Materials and methods: The toxicity study was performed in Wistar rats by oral administration. An acute toxicity study was done at the dose of 2000 mg/kg. In the sub-acute study, Wistar rats (10/sex/group) were administered via gavage 0 (control), 500, 1000, 2000 mg/kg body weight/day of WSE for 28 days. Among two additional satellite groups, one group did not receive any drug while the second group received 2000 mg/kg/day for 28 days. At the end of study, the animals sacrificed and their body weight, hematology, serum chemistry, and histopathology evaluation was done.
Results: In acute toxicity studies, oral LD50 of WSE in Wistar rats was greater than 2000 mg/kg body weight. Compared to the control group in sub-acute toxicity study, administration of extract did not show any toxicologically significant treatment related changes in clinical observations, ophthalmic examination, body weight gain, feed consumption, clinical pathology evaluation, and organ weight. Hematological and serum chemistry parameters were within the normal limits. Terminal necropsy did not reveal any treatment related gross or histopathological findings.
Conclusion: Based on this study, the no-observed-adverse-effect-level of WSE is 2000 mg/kg body weight, the highest level tested.
Inability of pancreatic β-cells to make sufficient insulin to control blood sugar is a central feature of the aetiology of most forms of diabetes. In this review we focus on the deleterious effects of oxidative stress and ER stress on β-cell insulin biosynthesis and secretion, and on inflammatory signalling and apoptosis with a particular emphasis on type 2 diabetes. We argue that oxidative stress and ER stress are closely entwined phenomenon fundamentally involved in β-cell dysfunction, by direct effects on insulin biosynthesis and due to consequences of the ER stress-induced unfolded protein response. We summarise evidence that, although these phenomenon can be driven by intrinsic β-cell defects in rare forms of diabetes, in type 2 diabetes β-cell stress is driven by a range of local environmental factors including increased drivers of insulin biosynthesis, glucolipotoxicity and inflammatory cytokines. We describe our recent findings that a range of inflammatory cytokines contribute to β-cell stress in diabetes, and our discovery that IL-22 protects β-cells from oxidative stress regardless of the environmental triggers, and can correct much of diabetes pathophysiology in animal models. Finally we summarise evidence that β-cell dysfunction is reversible in type 2 diabetes, and discuss therapeutic opportunities for relieving oxidative and ER stress and restoring glycaemic control.
Hypoglycaemic effects of the herb ashwagandha, Withania somnifera, using in vitro assays and its potential in preventing stress induced hyperglycaemia in rat (in vivo) were studied. W. somnifera roots were subjected to extraction using different solvents with increasing polarity. All the extracts were tested for hypoglycaemic effect using in vitro methods viz., glucose uptake by yeast cells, α-amylase inhibitory activity, glucose adsorption and diffusion. Chloroform and ethanolic extracts were more effective in increasing glucose uptake by yeast cells, inhibition of α-amylase activity, increasing glucose adsorption and decreasing diffusion compared to other extracts in in vitro study. In vivo hypoglycaemic action was investigated by treating adult male rats with different doses (5, 10, 20 mg/kg body weight) of ethanol and chloroform extracts prior to exposing them to a stress regime consisting of restraint (1h) followed by forced swimming exercise (15 minutes) after a gap of 4h. Chloroform and ethanolic extracts were potent in attenuating stress induced hyperglycaemia with a minimum effective dose of 10 mg/kg body weight. The study reveals that W. somnifera utilise different mechanisms to exert hypoglycaemic effect and has phytocomponent which can prevent stress induced hyperglycaemia. Hence phytocomponent present in these extracts may be a potential anti stress drug.
BACKGROUND:
Effective prevention is needed to combat the worldwide epidemic of type 2 diabetes. We investigated the long-term extent of beneficial effects of lifestyle intervention and metformin on diabetes prevention, originally shown during the 3-year Diabetes Prevention Program (DPP), and assessed whether these interventions reduced diabetes-associated microvascular complications.
METHODS:
The DPP (1996-2001) was a randomised trial comparing an intensive lifestyle intervention or masked metformin with placebo in a cohort selected to be at very high risk of developing diabetes. All participants were offered lifestyle training at the end of the DPP. 2776 (88%) of the surviving DPP cohort were followed up in the DPP Outcomes Study (DPPOS, Sept 1, 2002, to Jan 2, 2014) and analysed by intention to treat on the basis of their original DPP assignment. During DPPOS, the original lifestyle intervention group was offered lifestyle reinforcement semi-annually and the metformin group received unmasked metformin. The primary outcomes were the development of diabetes and the prevalence of microvascular disease. For the assessment of microvascular disease, we used an aggregate microvascular outcome, composed of nephropathy, retinopathy, and neuropathy.
FINDINGS:
During a mean follow-up of 15 years, diabetes incidence was reduced by 27% in the lifestyle intervention group (hazard ratio 0·73, 95% CI 0·65-0·83; p<0·0001) and by 18% in the metformin group (0·82, 0·72-0·93; p=0·001), compared with the placebo group, with declining between-group differences over time. At year 15, the cumulative incidences of diabetes were 55% in the lifestyle group, 56% in the metformin group, and 62% in the placebo group. The prevalences at the end of the study of the aggregate microvascular outcome were not significantly different between the treatment groups in the total cohort (placebo 12·4%, 95% CI 11·1-13·8; metformin 13·0%, 11·7-14·5; lifestyle intervention 11·3%, 10·1-12·7). However, in women (n=1887) the lifestyle intervention was associated with a lower prevalence (8·7%, 95% CI 7·4-10·2) than in the placebo (11·0%, 9·6-12·6) and metformin (11·2%, 9·7-12·9) groups, with reductions in the lifestyle intervention group of 21% (p=0·03) compared with placebo and 22% (p=0·02) compared with metformin. Compared with participants who developed diabetes, those who did not develop diabetes had a 28% lower prevalence of microvascular complications (relative risk 0·72, 95% CI 0·63-0·83; p<0·0001).
INTERPRETATION:
Lifestyle intervention or metformin significantly reduced diabetes development over 15 years. There were no overall differences in the aggregate microvascular outcome between treatment groups; however, those who did not develop diabetes had a lower prevalence of microvascular complications than those who did develop diabetes. This result supports the importance of diabetes prevention.
FUNDING:
National Institute of Diabetes and Digestive and Kidney Diseases.
Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users.
Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions.
The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
Aim of this study was to define oral dose range and treatment regimen of a pharmaceutically well-standardized Withania somnifera root extract (WS) potentially useful for treatments of diabetes-associated comorbidities. Normal and diabetic male mice were treated daily with graded oral doses of WS for 10 consecutive days. On the 1st, 5th, 7th, and 10th days of treatments, the animals were subjected to a foot shock stress-triggered hyperthermia tests. Changes in body weights and basal core temperatures of experimental animals during the course of the experiments were also recorded. In addition, plasma glucose, insulin, and cortisol levels and weights of adrenal glands and spleen of diabetic animals were quantified after 10 daily WS doses. No statistically significant effects of a single oral dose of WS on any of the quantified parameters were observed even after its highest oral dose (400 mg/kg) tested. However, dose and duration of treatment dependant protective effects of WS against body weight losses and elevated core temperatures caused by daily handling and intermittent foot shock stress, as well as against stress-triggered transient hyperthermia were observed in both normal and diabetic mice after its repeated daily doses. Dose dependant efficacy of the extract against elevated plasma glucose, insulin, and cortisol levels, and alterations in adrenal gland and spleen weights of diabetic animals were apparent after its 10 daily doses. Reported observations add further experimental evidence justifying traditionally known medicinal uses of Withania somnifera for treatment of mental health problems commonly associated with numerous lifestyle-related chronic diseases.
insulin resistance, dyslipidemia, β-cell dysfunction, impaired glucose tolerance and ultimately leading to T2DM. Chronic oxidative stress, hyperglycemia and dyslipidemia are particularly dangerous for β-cells from lowest levels of antioxidant, have high oxidative energy requirements, decrease the gene expression of key β-cell genes and induce cell death. If β-cell functioning is impaired, it results in an under production of insulin, impairs glucose stimulated insulin secretion, fasting hyperglycemia and eventually the development of T2DM. Core tip: Oxidative stress is underling in the development of cardiovascular disease, type 2 diabetes mellitus (T2DM) and diabetic complications. Increased oxidative stress appears to be a deleterious factor leading to insulin resistance, dyslipidemia, β-cell dysfunction, impaired glucose tolerance and ultimately leading to T2DM. Tangvarasittichai S. Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World J Diabetes 2015; 6(3): 456-480 Available from:
Background:
We investigated the effects of Withania somnifera root (WS) on insulin resistance, tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) in fructose-fed rats.
Methods:
Forty-eight Wistar-Albino male rats were randomly divided into four groups (n=12); Group I as control, Group II as sham-treated with WS by 62.5mg/g per diet, Group III fructose-fed rats received 10%W/V fructose, and Group IV fructose- and WS-fed rats. After eight weeks blood samples were collected to measure glucose, insulin, IL-6, and TNF-α levels in sera.
Results:
Blood glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-R), IL-6, and TNF-α levels were all significantly greater in the fructose-fed rats than in the controls. Treatment with WS significantly (P < 0.05) inhibited the fructose-induced increases in glucose, insulin, HOMA-R, IL-6, and TNF-α.
Conclusion:
Our data suggest that WS normalizes hyperglycemia in fructose-fed rats by reducing inflammatory markers and improving insulin sensitivity.
Male reproductive dysfunctions and infertility are the common consequences of overt diabetes. Available evidence support oxidative stress to be the underlying mechanism for the manifestation of testicular complications during diabetes. In the present study, we assessed the attenuating effects of Withania somnifera root extract (WS) on diabetes-induced testicular oxidative disturbances in prepubertal rats. Four-week-old prepubertal rats were assigned into nondiabetic control, streptozotocin (STZ)-treated and STZ + WS supplemented (500 mg/kg b.w./d, oral, 15 days) groups. Experimental diabetes was induced by a single intraperitoneal injection of STZ (90 mg/kg b.w). Terminally, all animals were killed, and markers of oxidative stress were determined in the testis cytosol and mitochondrial fraction. Severe hyperglycemia and regression in testis size were apparent in diabetic rats. A decline in antioxidant defenses with subsequent elevation in the generation of reactive oxygen species and lipid peroxidation was discernible in testis cytosol and mitochondria of diabetic prepubertal rats, which was significantly reversed by WS. However, there was partial restoration of glucose-6-phosphate dehydrogenase, lactate dehydrogenase, and 3-beta hydroxysteroid dehydrogenase activities in testis of diabetic prepubertal rats administered with WS. Taken together, data accrued suggest the potential of WS to improve diabetes-induced testicular dysfunctions in prepubertal rats.
Phytochemical investigations on the chloroform soluble fraction of the whole plant of Withania somnifera led to the isolation of 20β hydroxy-1-oxo(22R)-witha-2,5,24 trienolide 1, (20R, 22R-14α, 20α)-dihydroxy-1-oxowitha-2,5,16,24 tetraenolide 2, and (20R, 22R)-1-oxo-5α, 8β-dihydroxywitha-6α, 7β-epoxide-2,24-dienolide (withasomilide) 3. The structures of these compounds were confirmed through spectral studies in comparison with data in the literature. These isolated compounds (1–3) exhibited potent inhibition against α-glucosidase with IC50 values of 98.60, 38.20, and 40.65 μg/ml respectively.
Background
It has been reported that hyperglycemia can induce endothelial dysfunction via increased oxidative stress and that it plays a central role in the development of atherosclerosis and coronary heart disease. Phyllanthus emblica (Emblica officinalis, amla) is known for its antioxidant and antihyperlipidemic activity. The present study compared the effects of an aqueous extract of P. emblica (highly standardized by high-performance liquid chromatography to contain low molecular weight hydrolyzable tannins, ie, emblicanin A, emblicanin B, pedunculagin, and punigluconin) versus those of atorvastatin and placebo on endothelial dysfunction and biomarkers of oxidative stress in patients with type 2 diabetes.
Methods
Eligible patients were randomized to receive either P. emblica 250 mg twice daily, P. emblica 500 mg twice daily, atorvastatin 10 mg in the evening and matching placebo in the morning, or placebo twice daily for 12 weeks. The primary efficacy parameter was the change in endothelial function identified on salbutamol challenge at baseline and after 12 weeks of treatment. Secondary efficacy parameters were changes in biomarkers of oxidative stress (malondialdehyde, nitric oxide, and glutathione), high sensitivity C-reactive protein levels, the lipid profile, and glycosylated hemoglobin (HbA1c) levels. Laboratory safety parameters were measured at baseline and after 12 weeks of treatment.
Results
Eighty patients completed the study. Treatment with P. emblica 250 mg, P. emblica 500 mg, or atorvastatin 10 mg produced significant reductions in the reflection index (−2.25%±1.37% to −9.13%±2.56% versus −2.11%±0.98% to −10.04%±0.92% versus −2.68%±1.13% to −11.03%±3.93%, respectively), suggesting improvement in endothelial function after 12 weeks of treatment compared with baseline. There was a significant improvement in biomarkers of oxidative stress and systemic inflammation compared with baseline and placebo. Further, the treatments significantly improved the lipid profile and HbA1c levels compared with baseline and placebo. All treatments were well tolerated.
Conclusion
Both atorvastatin and P. emblica significantly improved endothelial function and reduced biomarkers of oxidative stress and systemic inflammation in patients with type 2 diabetes mellitus, without any significant changes in laboratory safety parameters.
Ashwagandha (Withania somnifera) (WS), a "rasayana" drug, is recommended for balavardhan and mamsavardhan. The study was intended to evaluate dose-related tolerability, safety, and activity of WS formulation in normal individuals. The design was prospective, open-labeled, variable doses in volunteers. Eighteen apparently healthy volunteers (12M:6F, age:18-30 years, and BMI: 19-30) were enrolled. After baseline investigations, they received WS capsules (Rx) (aqueous extract, 8:1) daily in two divided doses with increase in daily dosage every 10 days for 30 days (750 mg/day ×10 days, 1 000 mg/day × 10 days, 1 250 mg/day × 10 days). Volunteers were assessed for symptoms/signs, vital functions, hematological and biochemical organ function tests. Muscle activity was measured by hand grip strength, quadriceps strength, and back extensor force. Exercise tolerance was determined using cycle ergometry. Lean body weight and fat% were computed from skin fold thickness measurement. Adverse events were recorded, as volunteered by the subjects. Repeated measures ANOVA, McNemar's test, and paired t test were employed. All but one volunteer tolerated WS without any adverse event. One volunteer showed increased appetite, libido, and hallucinogenic effects with vertigo at the lowest dose and was withdrawn from study. In six subjects, improvement in quality of sleep was found. Organ function tests were in normal range before and after the intervention. Reduction in total- and LDL- cholesterol and increase of strength in muscle activity was significant. Total body fat percentage showed a reduction trend. WS, in escalated dose, was tolerated well. The formulation appeared safe and strengthened muscle activity. In view of its traditional Rasayana use, further studies are planned to evaluate potential of this drug in patients of sarcopenia.
Withania somnifera, commonly known as Ashwagandha, is an important medicinal plant that has been used in Ayurvedic and indigenous medicine for over 3,000 years. In view of its varied therapeutic potential, it has also been the subject of considerable modern scientific attention. The major chemical constituents of the Withania genus, the withanolides, are a group of naturally occurring C28-steroidal lactone triterpenoids built on an intact or rearranged ergostane framework, in which C-22 and C-26 are appropriately oxidized to form a six-membered lactone ring. In recent years, numerous pharmacological investigations have been carried out into the components of W. somnifera extracts. We present here an overview of the chemical structures of triterpenoid components and their biological activity, focusing on two novel activities, tumor inhibition and antiangiogenic properties of withaferin A and the effects of withanolide A on Alzheimer's disease. The most recent attempts in biotechnological production of withanolides are also discussed.
Type 2 diabetes is regarded as inevitably progressive, with irreversible beta cell failure. The hypothesis was tested that both beta cell failure and insulin resistance can be reversed by dietary restriction of energy intake.
Eleven people with type 2 diabetes (49.5 ± 2.5 years, BMI 33.6 ± 1.2 kg/m(2), nine male and two female) were studied before and after 1, 4 and 8 weeks of a 2.5 MJ (600 kcal)/day diet. Basal hepatic glucose output, hepatic and peripheral insulin sensitivity and beta cell function were measured. Pancreas and liver triacylglycerol content was measured using three-point Dixon magnetic resonance imaging. An age-, sex- and weight-matched group of eight non-diabetic participants was studied.
After 1 week of restricted energy intake, fasting plasma glucose normalised in the diabetic group (from 9.2 ± 0.4 to 5.9 ± 0.4 mmol/l; p = 0.003). Insulin suppression of hepatic glucose output improved from 43 ± 4% to 74 ± 5% (p = 0.003 vs baseline; controls 68 ± 5%). Hepatic triacylglycerol content fell from 12.8 ± 2.4% in the diabetic group to 2.9 ± 0.2% by week 8 (p = 0.003). The first-phase insulin response increased during the study period (0.19 ± 0.02 to 0.46 ± 0.07 nmol min(-1) m(-2); p < 0.001) and approached control values (0.62 ± 0.15 nmol min(-1) m(-2); p = 0.42). Maximal insulin response became supranormal at 8 weeks (1.37 ± 0.27 vs controls 1.15 ± 0.18 nmol min(-1) m(-2)). Pancreatic triacylglycerol decreased from 8.0 ± 1.6% to 6.2 ± 1.1% (p = 0.03).
Normalisation of both beta cell function and hepatic insulin sensitivity in type 2 diabetes was achieved by dietary energy restriction alone. This was associated with decreased pancreatic and liver triacylglycerol stores. The abnormalities underlying type 2 diabetes are reversible by reducing dietary energy intake.
Several medicinal plants have been described to be beneficial for cardiac ailments in Ayurveda like Ashwagandha and Arjuna. Ashwagandha-categorised as Rasayanas, and described to promote health and longevity and Arjuna primarily for heart ailments. coronary artery disease, heart failure, hypercholesterolemia, anginal pain and can be considered as a useful drug for coronary artery disease, hypertension and ischemic cardiomyopathy.
There are no scientific clinical studies showing effect of both these drugs on exercise performance after regular administration when given as supplements The present study was therefore designed and performed to assess the effects of Withania somnifera (Ashwagandha) and Terminalia arjuna (Arjuna) individually and as a combination on maximum velocity, average absolute and relative Power, balance, maximum oxygen consumption (VO2 max) and blood pressure in humans.
Forty normal healthy. Subjects (either sex, mean age 20.6 ± 2.5yrs and mean Body Mass Index 21.9 ± 2.2) were recruited after written informed consent was obtained. Institutional Ethics Committee permission was also obtained. Thirty participants were assigned to experimental group of which 10 received standardized root extracts of Withania somnifera, 10 received standardized bark extract of Terminalia arjuna and the rest of the 10 received standardized root extract of Withania somnifera in addition to bark extract of Terminalia arjuna both. Both the drugs were given in the form of capsules (dosage 500mg/day for both the drugs). Ten participants received placebo (capsules filled with flour). All the subjects continued the regimen for 8 weeks. All variables were assessed before and after the course of drug administration
Our study showed that Withania somnifera increased velocity, power and VO2 max whereas Terminalia arjuna increased VO2 max and lowered resting systolic blood pressure. When given in combination, the improvement was seen in all parameters except balance and diastolic blood pressure.
Withania somnifera may therefore be useful for generalized weakness and to improve speed and lower limb muscular strength and neuro-muscular co-ordination. Terminalia arjuna may prove useful to improve cardio-vascular endurance and lowering systolic blood pressure. Both drugs appear to be safe for young adults when given for mentioned dosage and duration.
Use of botanicals in traditional medicines is quite well known, has a long history of safe usage and is acknowledged for its efficacy. Such usage in a well-documented nature, prescribed by traditional qualified physicians, has a history of usage both in Indian traditional medicine (Ayurveda, Unani and Siddha [AUS]) healthcare systems as well as traditional Chinese medicine (TCM). The Ayurvedic system is considered to have originated with the first treatise of Ayurveda, the Charaka Samhita (the Sanskrit word Sam.hitā meaning treatise, pharmacopoeia or medical compendium, written by the sage Charaka), which dates to around 1000 BCE (Tripathi, 2010). Subsequent to this, a large number of other treatises have been documented in Ayurveda that describe holistic healthcare science, descriptions of health and diseases, diagnostic methods, surgery procedures, treatment with diet, behavioural aspects and medicines. The last such treatment included medicines prepared using botanicals in an elaborate 188pharmaceutical approach called ‘Bheshaj Kalpana’ (Reddy 2015). Similarly, TCM Materia Medica has been documented since c. 425–536 (Gurib-Fakim 2006; Liao 2006). The drugs listed in such traditional medicine books demonstrate the long history of safe use, as any drug to enter one such Materia Medica is known to have undergone usage and observation for at least 50–60 years. Only those that have been found to have a good safety profile either as such or after specified processing methods deserved an entry in to such books. Other traditional systems of healthcare that are not so well documented continue to be used, including the Bhutanese system of medicine, Kampo medicine in Japan, African traditional medicine, Australian and Southeast Asian traditional medicine, to name a few. Table 10.1 lists a few authoritative books on traditional healthcare and medicine.
Ethnopharmacological relevance: Diabetes and hypertension are pathophysiologically related diseases that co-exist with a wider complex of metabolic diseases having similar set of risk factors. There are numerous ethnopharmacological evidences on the anti-diabetic and/or anti-hypertensive properties of medicinal plants from various parts of the world, which are used as therapies to concomitantly manage diabetes and hypertension. Aim of the review: This article reviewed findings on medicinal plants with both anti-diabetic and anti-hypertensive effects reported in same experimental study to facilitate the development of dual-acting therapies against diabetes and hypertension. Materials and methods: A literature search was carried out on different scientific search engines including, but not limited to “PubMed”, “Google Scholar”, “Scopus” and ScienceDirect to identify published data in which plants in same experimental studies were reported to possess both anti-hyperglycemic and anti-hypertensive effects. Subsequently, the anti-diabetic/anti-hypertensive potency ratio (ψ) of the medicinal plants was computed. Results: Sixty-four studies with 102 plant species matched the selection criteria. Members of the Fabaceae family were the most investigated plants, while the ψ greatly varied across the plants, with only 11 plants having a ψ ≃ 1. Withania somnifera Dunal was the only plant reported to show blood glucose-lowering and diuretic effects in humans, comparable to daonil. Caffeic acid, chlorogenic acid, caftaric acid, cichoric acid, verbascoside, leucosceptoside A, isoacteoside, fucoxanthin and nicotinamide were the reported dual acting anti-diabetic and anti-hypertensive compounds identified and/or isolated in the plants. Conclusions: This review suggests that medicinal plants possess varied therapeutic dynamics against hypertension and diabetes that could be exploited for the discovery of therapeutic preparation(s) or agent(s) for treating the two diseases.
Type 1 diabetes mellitus (T1DM) is one of the major metabolic disorders with life-long dependence on insulin. The present study was designed to evaluate the antioxidant and anti-diabetic potential of Withaferin A (WA), the active constituent of Withania somnifera in multiple low doses of Streptozotocin (MLD-STZ) induced T1DM. STZ (40 mg/Kg) was administered intraperitoneally (i.p.) for 5 consecutive days to male Swiss albino mice to induce T1DM. Mice were concurrently treated with WA (2 & 10 mg/Kg). Blood glucose levels, intraperitoneal glucose tolerance test, oxidative stress parameters were estimated biochemically (MDA, GSH) and immunohistochemically (Nrf2, NFκB). In addition, inflammatory cytokines, and insulin levels were quantified by ELISA method. Apoptosis was assessed by immunohistochemical staining for cleaved-caspase-3 and TUNEL assay. WA treatment significantly reduced the blood glucose levels and improved glucose clearance. Strikingly, we observed a significant reduction in the incidence of diabetes upon WA treatment and only 2 out of 8 (2/8 = 25%) animals were diabetic. WA ameliorated the MLD-STZ induced oxidative and nitrosative stress. Furthermore, WA exhibited promising anti-inflammatory effect as evident from reduction in the levels of IL-6 (p < 0.05) and TNF-α (p < 0.05) compared to diabetic mice. In addition, insulitis scoring and IHC for Nrf2 and NFκB indicated promising anti-diabetic effect. WA reduced MLD-STZ induced DNA fragmentation and apoptosis, further supporting the observed protective effect. We, to the best of our knowledge, report for the first time that WA can effectively combat MLD-STZ induced T1DM via modulation of Nrf2/NFκB signaling and holds substantial potential for therapy of T1DM.
Rapidly increasing aging population and environmental stressors are the two main global concerns of increasing incidence of a variety of pathologies in the modern society. The complex etiologies and pathologies cause major challenges to disease treatment. On the other hand, several herbs are known for their health-caring and disease-curing activities. Ashwagandha, a popular herb in Indian traditional home medicine, Ayurveda, has gathered increasing recognition in recent years when the chemically synthesized drugs for single target therapies showed limited success and adverse toxic effects. Ashwagandha is known as a powerful adaptogen and trusted to enhance function of the brain, reproductive system, cell-mediated immunity and increase the body's defense against disease, and possess anti-inflammatory, anticancer and anti-arthritic activities. In this book, for the first time, we provide a complete portrait on scientific understanding of the effects of Ashwagandha and its active principles for a variety of preventive and therapeutic activities.
Background
: Withania somnifera Dunal, commonly known as Indian ginseng, has been in use since ancient times as anti-stress agent, aphrodisiac, for impotence and infertility treatment.
Purpose
: To evaluate the efficacy and safety of W. somnifera treatment in infertile men.
Study design
: An evidence-based systematic review and meta-analysis using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.
Methods
: published literature was searched in PubMed/MEDLINE, EMBASE, Scopus, the Cochrane Library, and DHARA. Grey literature was assessed from the WHO International Clinical Trials Registry Platform (http://apps.who.int/trialsearch/) and the US National Institutes of Health (https://clinicaltrials.gov/).
Results
: Four clinical trials (comprising 5 publications: observational, n = 4; randomized controlled trial [RCT], n = 1) were included in the study. As only one RCT included, meta-analysis of RCT was not performed; however, systematically reviewed data demonstrated statistical (P ≤ 0.002 versus baseline) increase in sperm concentration (167%), semen volume (59%), and sperm motility (57%) in oligospermic males after 90 days of W. somnifera therapy, as well, serum testosterone (17%) and luteinizing hormone (34%) levels. Meta-analysis of observational (versus pre-treatment) studies showed that W. somnifera treatment significantly improved semen parameters (semen volume: mean difference [MD], 0.28 ml; 95% confidence interval [CI], 0.12 to 0.43; P = 0.0004; sperm concentration: MD, 13.57 million/ml; 95% CI, 11.12 to 16.01; P < 0.00001; sperm motility: MD, 8.50%; 95% CI, 7.36 to 9.63; P < 0.00001) with 14% of pregnancy outcome success rate in normozoospermic men. Meta-analysis findings also evidenced significant improvement in serum hormonal profile, oxidative biomarkers and antioxidant vitamins in seminal plasma. No adverse effects were reported in infertile men taking W. somnifera treatment.
Conclusion
: Due to a small number of eligible studies, the available data, though promising, are too limited to provide novel and sufficiently robust evidence of the benefits of W. somnifera in male infertility. Additional RCTs of high quality with a larger sample size are warranted to further strength clinical use of W. somnifera in treating male factor infertility. Future research also needs to elucidate the molecular mechanism(s) of W. somnifera as well its active principles in male infertility.
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.
Embelia ribes (ER) has been documented in Ayurveda for treating various diseases, including diabetes mellitus (DM). The present systematic review and meta-analysis evaluated the efficacy and safety of ER and its active bio-marker, embelin and its derivatives in the treatment of DM. Literature search was performed in PubMed/MEDLINE, EMBASE, Scopus, ScienceDirect, Scifinder, and Google Scholar. Using Review Manager, meta-analysis of ER/embelin/derivatives of embelin versus diabetic control was performed with inverse-variance model, providing mean differences (MDs) and 95% confidence intervals (CIs). Heterogeneity was determined by I2 statistic. A total of 13 studies were included in the systematic review and meta-analysis, and were conducted in experimental rats. ER and embelin significantly (P ≤ 0.01) resorted blood glucose (MD, −231.30; CI, −256.79, −205.82; and MD, −154.70; CI, −168.65, −140.74) and glycosylated haemoglobin (MD, −6.36; CI, −8.33, −4.39; and MD,−4.68; CI, −7.76, −1.60), respectively. Meta-analysis findings also reported considerable restoration of insulin, lipid profile, haemodynamic parameters, serum and oxidative stress markers. The derivatives of embelin, 6-bromoembelin and vilangin, also improved diabetic condition. In addition, treatments also ameliorated body weight changes due to diabetes. The present systematic review and meta-analysis supports scientific evidence for the antidiabetic activity of ER/embelin/derivatives of embelin. However, further research is warranted in clinical trials to validate the present findings.
Hypothalamus, the primary brain region for glucose sensing, is severely affected by oxidative stress in diabetes mellitus. Oxidative stress in this region of brain may cause severe impairment in neuronal metabolic functions. Mitochondria are prominent targets of oxidative stress and the combination of increased oxidative stress and mitochondrial dysfunctions may further decline hypothalamic neuronal functions. In the present study we examined the oxidative damage response, antioxidative responses and mitochondrial membrane permeability transition in hypothalamus of streptozotocin-treated diabetic rats. Our results show that streptozotocin significantly increases hypothalamic lipid peroxidation, protein carbonyl content while glutathione peroxidase and reduced glutathione were declined. Mitochondrial impairment marked by an increase in mitochondrial membrane permeabilization was seen following streptozotocin treatment in the hypothalamus. The oral administration of Withania somnifera root extract stabilized mitochondrial functions and prevented oxidative damage in the hypothalamus of diabetic rat. These findings suggest an increase in the oxidative stress and decline in antioxidative responses in the hypothalamus of streptozotocin treated diabetic rats. Withania somnifera root extract was found useful in reducing oxidative stress and mitochondrial impairment in hypothalamus of diabetic rat.
Ethnopharmacological relevance: Chyawanprash (CP), a traditional immune booster recipe, has a long history of ethnic origin, development, household preparation and usage. There are even mythological stories about the origin of this recipe including its nomenclature. In the last six decades, CP, because of entrepreneurial actions of some research Vaidyas (traditional doctors) has grown to industrial production and marketing in packed forms to a large number of consumers/patients like any food or health care product. Currently, CP has acquired a large accepted user base in India and in a few countries out-side India.
Aim of the study: Authoritative texts, recognized by the Drugs and Cosmetics Act of India, describe CP as an immunity enhancer and strength giver meant for improving lung functions in diseases with compromised immunity. This review focuses on published clinical efficacy and safety studies of CP for correlation with health benefits as documented in the authoritative texts, and also briefs on its recipes and processes.
Materials and methods: Authoritative texts were searched for recipes, processes, and other technical details of CP. Labels of marketing CP products (Indian) were studied for the health claims. Electronic search for studies of CP on efficacy and safety data were performed in PubMed/MEDLINE and DHARA (Digital Helpline for Ayurveda Research Articles), and Ayurvedic books were also searched for clinical studies.
Results: The documented clinical studies from electronic databases and Ayurvedic books evidenced that individuals who consume CP regularly for a definite period of time showed improvement in overall health status and immunity. However, most of the clinical studies in this review are of smaller sample size and short duration. Further, limitation to access and review significant data on traditional products like CP in electronic databases was noted.
Conclusions: Randomized controlled trials of high quality with larger sample size and longer follow-up are needed to have significant evidence on the clinical use of CP as immunity booster. Additional studies involving measurement of current biomarkers of immunity pre- and post-consumption of the product as well as benefits accruing with the use of CP as an adjuvant are suggested.
The increasing global prevalence of obesity and its associated disorders points to an urgent need for the development of novel and effective therapeutic strategies that induce healthy weight loss. Obesity is characterized by hyperleptinemia and central leptin resistance. In an attempt to identify compounds that could reverse leptin resistance and thus promote weight loss, we analyzed a library of small molecules that have mRNA expression profiles similar to that of celastrol, a naturally occurring compound that we previously identified as a leptin sensitizer. Through this process, we identified another naturally occurring compound, withaferin A, that also acts as a leptin sensitizer. We found that withaferin-A treatment of mice with diet-induced obesity (DIO) resulted in a 20-25% reduction of body weight, while also decreasing obesity-associated abnormalities, including hepatic steatosis. Withaferin-A treatment marginally affected the body weight of ob/ob and db/db mice, both of which are deficient in leptin signaling. In addition, withaferin A, unlike celastrol, has beneficial effects on glucose metabolism that occur independently of its leptin-sensitizing effect. Our results show that the metabolic abnormalities of DIO can be mitigated by sensitizing animals to endogenous leptin, and they indicate that withaferin A is a potential leptin sensitizer with additional antidiabetic actions.
Background:
The effect of the interaction between type 2 diabetes and dyslipidemia on inflammation and lipid peroxidation (LPO) has not been assessed.
Aim:
To investigate whether diabetes coupled with dyslipidemia alters oxidative metabolism leading to increased LPO products and inflammatory status.
Methods:
100 patients were divided into four groups based upon diabetic and dyslipidemic status: poorly controlled diabetes with dyslipidemia (DM-PC/D), well-controlled diabetes with dyslipidemia (DM-WC/D), normoglycemic individuals with dyslipidemia (NG/D), and normoglycemic individuals without dyslipidemia (NG/ND). Plasma was evaluated for an LPO product (MDA), antioxidant levels and inflammatory cytokines.
Results:
Diabetics presented significantly higher levels of LPO (p<0.05) and the DM-PC/D had higher levels of proinflammatory cytokines and MDA in the plasma in comparison with normoglycemics (p<0.05). Interestingly IL1-β, IL-6, and TNF-α in DM-WC/D were not statistically different from those in DM-PC/D. Normoglycemic individuals with dyslipidemia presented significantly increased levels of IL-6 and TNF-α when compared to normoglycemic without dyslipidemia (p<0.05). MDA levels were also positively correlated with the presence of DM complications (r=0.42, p<0.01).
Conclusions:
These findings show that dyslipidemia is associated with an increased inflammatory status, even in well-controlled diabetics and in normoglycemics. Our results suggest that lipid metabolism and peroxidation are important for the development of inflammation, which is elevated in several complications associated with diabetes.
Background:
Insulin resistance is a metabolic disorder which affects the diabetes mellitus pathophysiology and alters the cell excitability. This study has been designed to evaluate the anti-nociceptive and anti-inflammatory effects of chronic administration of Withania somnifera root (WSR) in fructose drinking water rats.
Methods:
An experiment was carried out on 48 Wistar-Albino male rats, weighting 200±30 g, which were divided into six groups (n=8): control group (C), control morphine (CM), W. somnifera group (WS) which received WSR (62.5 mg/g diet), W. somnifera naloxone group (WSN) which received WSR and naloxone, fructose (F) group which received fructose drinking water and FWS group which received fructose-enriched drinking water and WSR during the trial period. A biphasic pain response was induced after intraplantar injection of formalin (50 μL, 1%). Pain behavior was measured using Dubuisson methods. The obtained data were analyzed by SPSS software V. 18, using ANOVA and Tukey test. Results were expressed as mean±SD. Statistical differences were considered significant at p<0.05.
Results:
The results showed that the insulin resistance index, blood sugar, insulin, IL-6, TNF-α, and acute and chronic pain score in the F group were significantly increased in comparison with the control group, but these parameters in the FWS group were significantly decreased compared with the F group (p<0.001).
Conclusions:
Our findings indicated that chronic oral administration of WSR has analgesic and anti-inflammatory effects in fructose drinking water rats and causes improved insulin resistance index.
Hypothalamus, the primary brain region for glucose sensing, is severely affected by oxidative stress in diabetes mellitus. Oxidative stress in this region of brain may cause severe impairment in neuronal metabolic functions. Mitochondria are prominent targets of oxidative stress and the combination of increased oxidative stress and mitochondrial dysfunctions may further decline hypothalamic neuronal functions. In the present study we examined the oxidative damage response, antioxidative responses and mitochondrial membrane permeability transition in hypothalamus of streptozotocin-treated diabetic rats. Our results show that streptozotocin significantly increases hypothalamic lipid peroxidation, protein carbonyl content while glutathione peroxidase and reduced glutathione were declined. Mitochondrial impairment marked by an increase in mitochondrial membrane permeabilization was seen following streptozotocin treatment in the hypothalamus. The oral administration of Withania somnifera root extract stabilized mitochondrial functions and prevented oxidative damage in the hypothalamus of diabetic rat. These findings suggest an increase in the oxidative stress and decline in antioxidative responses in the hypothalamus of streptozotocin treated diabetic rats. Withania somnifera root extract was found useful in reducing oxidative stress and mitochondrial impairment in hypothalamus of diabetic rat.
Excessive caloric intake, hyperglycemia, irregular blood lipid levels and resulting oxidative stress are accepted etiologies of Diabetes mellitus (DM) and associated co-morbidities including cardiovascular disease (CVD) and obesity (OB). These diseases are fast becoming leading causes of mortality in the developed and developing world. One important strategy for managing DM is managing postprandial hyperglycemia by reducing the digestion of carbohydrates by α-glucosidases. The risk factors for CVD and obesity can further be managed by regulating postprandial increases in blood triglyceride and fatty acid levels by modulating the activity of lipase. We investigated the potential of 18 different herbs, spices and medicinal plants (HSMP) commonly used in traditional medicine to reduce the energy harvest capacity of the mammalian gut by α-glucosidases and lipases in different model systems. In addition, we also assessed their abilities to confer antioxidant protection in biological systems. Our results indicate that several HSMP had the ability to prevent the digestion of carbohydrates by inhibiting α-amylase, maltase and sucrase. These HSMP were also effective in inhibiting the activity of lipase and therefore digestion of triglycerides in the mammalian gut. Based on our results, we have identified HSMP from different traditional medicines that can be used as an alternative and complimentary strategy to manage risk factors of DM and associated co-morbidities.
Withania somnifera, also called 'Indian ginseng', is an important medicinal plant of the Indian subcontinent. It is widely used, singly or in combination, with other herbs against many ailments in Indian Systems of Medicine since time immemorial. Withania somnifera contains a spectrum of diverse phytochemicals enabling it to have a broad range of biological implications. In preclinical studies, it has shown anti-microbial, anti-inflammatory, anti-tumor, anti-stress, neuroprotective, cardioprotective, and anti-diabetic properties. Additionally, it has demonstrated the ability to reduce reactive oxygen species, modulate mitochondrial function, regulate apoptosis, and reduce inflammation and enhance endothelial function. In view of these pharmacologic properties, W. somnifera is a potential drug candidate to treat various clinical conditions, particularly related to the nervous system. In this review, we summarize the pharmacologic characteristics and discuss the mechanisms of action and potential therapeutic applications of the plant and its active constituents.
OBJECTIVES:
Withania somnifera has been in use for several thousand years in Ayurveda to treat various neurological disorders. There is, however, not much scientific data on its protective role in neuronal pathology specifically against brain oxidative stress. Hence, an attempt is made in this work for systematic review and meta-analysis of W. somnifera on neurobehavioural disorders induced by brain oxidative stress in rodents.
METHODS:
A systematic search of the effect of W. somnifera on brain oxidative stress-induced neuronal pathology was performed using electronic databases. The systematic review was performed on neurobehavioural parameters, whereas meta-analysis of W. somnifera effect was done on oxidative stress markers (superoxide dismutase, catalase, glutathione peroxidase, glutathione and lipid peroxidation), nitrite, protein carbonyl, AchE, ChAT and Ach of rodent brain. Data were analysed using Review Manager Software.
KEY FINDINGS:
Twenty-eight studies were selected based upon the inclusion and exclusion criteria. W. somnifera appreciably inhibited the neurological abnormalities due to oxidative stress in rodent brain produced by different physical and chemical stimuli. W. somnifera also significantly restored the altered oxidative and other stress markers in different parts of rodent brain.
SUMMARY:
The systematic review provides scientific evidence for the traditional claim of W. somnifera use in different neurological aliments. However, future clinical trials are mandated to establish the therapeutic efficacy and safety in human beings.
KEYWORDS: Indian ginseng; antioxidant; meta-analysis; neuropathology; oxidative stress
The incretin hormone glucagon-like peptide 1 (GLP-1), proposed as a new target for the treatment of type 2 diabetes, is rapidly cleaved by dipeptidyl peptidase-IV enzyme (DPP-IV/CD26). DPP-IV inhibitors enhance circulating GLP-1 level, which in turn resulted into improved glucose tolerance and insulin secretion. The present study was designed to evaluate DPP-IV inhibitory activities vis a vis anti-peroxidative potential, if any, in two antidiabetic plants. We studied in vitro DPP-IV inhibition; DPPH radical scavenging potential; ß-carotene bleaching; reducing power and total phenolics content at the varying concentrations (0.1 – 1 mg/ml) in the extracts of W. somnifera (WS) root and T. foenum-graecum (TFG) seeds. Methanolic extract (0.5 mg/ml) of WS inhibited DPP-IV activities (69.7 ±0.56%) at greater extent than that of TFG (51.8±1.24%), as compared to control. WS extract contains relatively higher amount of total phenolics, elevated DPPH free radical scavenging potential and pronounced reducing power efficacy than that of TFG. The result of present study ravel that WS and TFG extracts contain some novel DPP-IV inhibitors with antiperoxidative potential and could be developed as therapeutic molecules for type 2 diabetes mellitus
IN BRIEF
Individuals with type 2 diabetes have a higher incidence of liver function test abnormalities than individuals who do not have diabetes. Mild chronic elevations of transaminases often reflect underlying insulin resistance. Elevation of transaminases within three times the upper limits of normal is not a contraindication for starting oral antidiabetic or lipid-modifying therapy. In contrast, antidiabetic agents have generally been shown to decrease alanine aminotransferase levels as tighter blood glucose levels are achieved.
The aim of the present study was to investigate the effects of Withania somnifera (WS) on lipid peroxidation (LPO), activities of both non-enzymatic and enzymatic antioxidants and histopathological examination of pancreas in type 2 diabetic rats. Type 2 diabetes was induced by single intraperitoneal injection of STZ (100 mg/kg) to 2 days old rat pups. Oxidative stress was measured by tissue LPO levels, reduced glutathione (GSH) contents and by enzymatic activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT). Administration of WS to type 2 diabetic rats caused a significant decrease in blood glucose and tissue LPO levels with significant increase in GSH contents when compared with the type 2 diabetic control rats. In addition, WS treated rats also showed a significant increase in the activities of antioxidant enzymes namely GPx, GR, GST, SOD and CAT when compared with type 2 diabetic control rats. Significant reduction in the number and size of pancreatic beta-cells were preserved to near normal morphology by the administration of WS in type 2 diabetic rats as evident from histopathological examination. The results obtained clearly indicate that WS has shown strong free radical scavenging activity and helped in improving the non-enzymatic and enzymatic antioxidants in type 2 diabetic rats.
Increased production of reactive oxygen species (ROS) has been implicated in the pathogenesis of cardiovascular disease (CVD), while enhanced endogenous antioxidants has been proposed as a mechanism for regulating redox balance. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcriptional regulator of phase II antioxidant enzymes, and activation of Nrf2 has been suggested to be an important step in attenuating oxidative stress associated with CVD. A well-defined combination of five widely studied medicinal plants derived from botanical sources [Bacopa monniera, Silybum marianum (milk thistle), Withania somnifera (Ashwagandha), Camellia sinensis (green tea), and Curcuma longa (turmeric)] has been shown to activate Nrf2 and induce phase II enzymes through the antioxidant response element (ARE). The purpose of these experiments was to determine if treatment of cardiomyocytes with this phytochemical composition, marketed as Protandim®, activates Nrf2, induces phase II detoxification enzymes, and protects cardiomyocytes from oxidant-induced apoptosis in a Nrf2-dependent manner. In cultured HL-1 cardiomyocytes, phytochemical treatment was associated with nuclear accumulation of Nrf2, significant induction of phase II enzymes, and concomitant protection against hydrogen peroxide-induced apoptosis. The protection against oxidant stress was abolished when Nrf2 was silenced by shRNA, suggesting that our phytochemical treatment worked through the Nrf2 pathway. Interestingly, phytochemical treatment was found to be a more robust activator of Nrf2 than oxidant treatment, supporting the use of the phytochemicals as a potential treatment to increase antioxidant defenses and protect heart cells against an oxidative challenge.
Obesity, metabolic syndrome, and diabetes mellitus are increasing in epidemic proportions globally. Prameha is a syndrome described in the ancient Ayurvedic texts that includes clinical conditions involved in obesity, prediabetes, diabetes mellitus, and metabolic syndrome.
Integrating the theory and modalities of Ayurveda in the management of these disorders may prove to be beneficial. Even though Prameha is a Tridoshaja Vyadhi (a disease involving all three of the psychophysiologic principles known as Doshas [i.e., Vata, Pitta, and Kapha]), it is basically a disease with Kapha predominance.
There are 20 subtypes of Prameha due to the interaction of the three Doshas and 10 Dushyas (disturbed functioning of the principles that support the various bodily tissues); several of these subtypes have sweet urine, whereas some of them have different coloration of the urine, highlighting the inflammatory conditions involved in the metabolic syndrome. This disease has close ties to Sthaulya (i.e., obesity). With regard to diabetes mellitus, Sahaja Prameha and Jatah Pramehi correlate with type 1 diabetes; Apathyanimittaja Prameha correlates with type 2 diabetes. Madhumeha is a subtype of Vataja Prameha (Prameha with Vata predominance) that can occur as the terminal stage of type 2 diabetes (in which insulin is required), or as type 1 diabetes beginning in early childhood. The latter is defined as Jatah Pramehi Madhumehino in Charaka Samhita, one of the classical Ayurvedic texts.
Various dietary, lifestyle, and psychologic factors are involved in the etiology of Prameha, particularly in relation to disturbances in fat and carbohydrate metabolism. The ancient Ayurvedic knowledge regarding Prameha can be utilized to expand the current understanding of obesity, metabolic syndrome, and diabetes.