Ashwagandha Extract Research Articles

Short-term influence of Immufen™ on mild allergic rhinitis: a randomized, double-blind, placebo-controlled study.

Allergic rhinitis (AR) is an IgE-mediated reaction to inhaled allergens, and is a prominent health concern affecting approximately 400 million people worldwide. A comprehensive understanding of AR's pathophysiology is imperative for developing novel therapies, especially considering its frequent co-morbidity with asthma and conjunctivitis. The escalating prevalence of AR is correlated with increased urbanization and environmental pollutants, recognized as prominent contributing factors. Dysregulation in immune networks, Th1/Th2 cytokine imbalance, activation of mast cells and eosinophils are implicated in AR progression. Classic AR symptoms include nasal congestion, nasal itching, rhinorrhea, and sneezing which significantly impact the quality of life, social interactions, and workplace productivity. This randomized, double-blind, placebo-controlled, three-arm, three-sequence study was aimed to assess the efficacy of supplementation of a co-delivery form of turmeric extract with ashwagandha extract (CQAB) in comparison with a bioavailable curcumin (CGM) and placebo in alleviating AR symptoms and enhancing the quality of life in individuals with mild AR. Participants received either placebo, CGM, or CQAB twice/day for 28 days, and subjective measures were recorded at the baseline and at the end of study. CQAB supplementation demonstrated a significant (P < 0.05) improvement in Total Nasal Symptom Score (TNSS) compared to placebo and CGM. Furthermore, CQAB administration resulted in enhanced sleep quality (P < 0.05) as evaluated by the BIS questionnaire, heightened energy levels, and decreased fatigue and overall mood disturbance (POMS-SF) compared to both placebo and CGM. The results suggests that CQAB has the potential to be used as a dietary supplement in alleviating AR discomforts. https://ctri.nic.in/Clinicaltrials/login.php; Identifier CTRI/2021/01/030355.

Evaluation of Withania somnifera (L.) Dunal (Ashwagandha) on Physical Performance, Biomarkers of Inflammation, and Muscle Status in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Study.

Sarcopenia is associated with chronic inflammation, a sedentary lifestyle, and ageing.However, there exists no drug, which is safe and effective for long-term use. Ashwagandha (Withaniasomnifera (L.) Dunal) has the potential to fill this therapeutic gap based on its efficacy and safety profile; hence, the present study was planned to evaluate its effect on inflammatory biomarkers and muscle status in healthy volunteers. A prospective, double-blind, randomized, placebo-controlled clinical study was conducted to evaluate the effects of Ashwagandha extract in healthy volunteers (February 2021 to May 2022) who received either Ashwagandha extract tablets 250 mgor a placebo twicedaily for 60 days. The physical performance on a bicycle ergometer, inflammatory/muscle status biomarkers, body composition, reaction time, hemogram, and organ function tests was assessed at baseline, day 30, and day 60. In the Ashwagandha group, there was a statistically significant (p<0.05) improvement in total distance travelled (Ashwagandha 2.85 ± 0.54 km vs placebo 2.16 ± 0.62 km), average speed achieved (Ashwagandha 25.6 ± 5.7 km/hour vs placebo 22.2 ± 5.48 km/hour) on a bicycle ergometer from the baseline visit (V3) to the last visit (V7) as compared to the placebo group. The observations on hand-grip strength, back-leg press, skeletal muscle mass, and VO2 max showed an increasing trend from V3to V7, whereas the results of thethree inflammatory markers (hs-C-reactive protein (CRP) mg/L; IL-6; TNF-alpha ) and the muscle marker (myostatin)revealed a decreasing trend from V3 to V7 in the Ashwagandha group.Ashwagandha extract was found to be safe in healthy volunteers as evidenced by the clinical profile, laboratory investigations, and reaction time test. Ashwagandha extract supplementation was safe and effective in enhancing physical performance and strengthening muscle mass and could be a potential candidate for treating sarcopenia.

Effectiveness of Enriched Milk with Ashwagandha Extract and Tryptophan for Improving Subjective Sleep Quality in Adults with Sleep Problems: A Randomized Double-Blind Controlled Trial.

A randomized, double-blind and controlled study was conducted to assess the effectiveness of the intake of 250 mL of lactose-free skimmed milk enriched with ashwagandha (Withania somnifera) alone or combined with tryptophan vs. non-enriched milk (control) on the subjective quality of sleep in healthy adults with sleep problems. The duration of supplementation was 90 days. Fifty-two eligible subjects were assigned to the study arms of ashwagandha 250 mg, ashwagandha 250 mg plus tryptophan 175 mg, ashwagandha 600 mg, and control with 13 subjects in each group. It was hypothesized that ashwagandha plus tryptophan could be superior to ashwagandha alone for improving sleep-related variables. Changes in the visual analogue scale (VAS) for sleep quality were significantly higher in the three experimental groups as compared with controls (p = 0.014). Improvements in the subscales of the Pittsburg Sleep Quality Index (PSQI) were found in all groups, but between-group differences were not significant. In the index of insomnia severity, decreases were higher in the three experimental groups as compared with controls especially in the group of ashwagandha 600 mg. Daytime somnolence was also reduced in the three experimental groups. Changes in anxiety levels and Morningness-Eveningness Questionnaire were not observed. The study products did not elicit changes in body composition and were well tolerated and safe. The data did not support the hypothesis, as the combination of ashwagandha and tryptophan did not show greater benefits in improving sleep quality than ashwagandha alone. However, the results from the three experimental groups containing ashwagandha were more favorable compared to the placebo group.

Ashwagandha's Multifaceted Effects on Human Health: Impact on Vascular Endothelium, Inflammation, Lipid Metabolism, and Cardiovascular Outcomes-A Review.

Withania somnifera, commonly known as Ashwagandha, has been popular for many years. Numerous studies have shown that the extract of this plant, due to its wealth of active substances, can induce anti-inflammatory, neuroprotective, immunomodulatory, hepatoprotective, cardioprotective, anti-diabetic, adaptogenic, anti-arthritic, anti-stress, and antimicrobial effects. This review examines the impact of Ashwagandha extract on the vascular endothelium, inflammation, lipid metabolism, and cardiovascular outcomes. Studies have shown that Ashwagandha extracts exhibit an anti-angiogenic effect by inhibiting vascular endothelial growth factor (VEGF)-induced capillary sprouting and formation by lowering the mean density of microvessels. Furthermore, the results of numerous studies highlight the anti-inflammatory role of Ashwagandha extract, as the action of this plant causes a decrease in the expression of pro-inflammatory cytokines. Interestingly, withanolides, present in Ashwagandha root, have shown the ability to inhibit the differentiation of preadipocytes into adipocytes. Research results have also proved that W. somnifera demonstrates cardioprotective effects due to its antioxidant properties and reduces ischemia/reperfusion-induced apoptosis. It seems that this plant can be successfully used as a potential treatment for several conditions, mainly those with increased inflammation. More research is needed to elucidate the exact mechanisms by which the substances contained in W. somnifera extracts can act in the human body.

Ashwagandha under fire: A critical scientific analysis of regulatory decisions

Ashwagandha (Withania somnifera [L.] Dunal) is one of the most renowned Ayurvedic medicinal plants, extensively used in traditional Indian medicine systems such as Ayurveda, Siddha, Unani, and Sowa Rigpa for millennia. Its medicinal uses of the root are documented in ancient texts such as the Charaka samhita, Sushruta samhita, and various Nighantus. Recognized globally, Ashwagandha is included in numerous pharmacopoeias, including the Ayurvedic Pharmacopoeia of India (API), British Pharmacopoeia, and United States Pharmacopoeia. Despite its extensive use and documented benefits, Ashwagandha faced scrutiny in Denmark. The Danish Veterinary and Food Administration banned Ashwagandha based on a 2020 report by the Technical University of Denmark (DTU). This report has been criticized for its technical, scientific, and ethical flaws, including reliance on unverified sources and omission of significant data from authoritative compendiums such as the API. Notably, the report’s references often included studies that did not adhere to established standards for Ashwagandha extracts. Furthermore, the alleged abortifacient properties cited in the Danish report are not supported by extensive reviews of traditional texts and modern scientific literature, which indicates the safety of Ashwagandha when used appropriately. This article aims to provide a comprehensive evaluation of the Danish report, emphasizing the necessity of adhering to rigorous scientific standards and accurately representing historical and contemporary data on Ashwagandha.

Potential use of ashwagandha extract in storage of liquid boar semen

Potential use of ashwagandha extract in storage of liquid boar semen

Assessing the Efficacy and Biological Benefits of Withanolide-rich Withania somnifera Root Extract

The medicinal plant Withania somnifera, usually referred to as Ashwagandha, is a member of the Solanaceae family. The presence of Withanolides in the roots is responsible for a number of pharmacological effects in Ashwagandha. Withanolides have been demonstrated to be an effective neuronal, immune, anti-stress, and anti-cancer agent. However, Withanolides demonstrated limited permeability, lowering the bioavailability and efficacy of active compounds. The goal of the study was to ascertain the biological efficacy of Ashwagandha Composition, a blend of W. somnifera milk extract and water extract (1:1) with a high concentration of Withanolides (3-5%), at lower dosages with improved bioabsorption compared to pure Ashwagandha Hydro ethanolic extracts fortified with 2.5% withanolides. The W. somnifera Composition was assessed for its bioabsorption and bioefficacy by exploring its intestinal absorption capacity, Acetylcholinesterase Inhibition (82%), antioxidant potential (91%), glutathione reduction potential (15.6%), anti-inflammatory activity (87.2%), and anti-cancer activity. Additionally, Ashwagandha Composition was also evaluated for its safety profile. We found W. somnifera Composition (1:1) is more bioavailable and showed higher biological activity than the Ashwagandha Hydro ethanolic extract fortified with 2.5% withanolides (Ashwagandha extract). Hence, the W. somnifera a Composition can be used as a therapeutic medication once its safety concerns are addressed by in vivo trials.

Effects of Withania somnifera Extract in Chronically Stressed Adults: A Randomized Controlled Trial.

Stress is a known causative factor in modulating cognitive health, which overall well-being and quality of life are dependent on. Long-term stress has been shown to disrupt the balance of the hypothalamic-pituitary-adrenal (HPA) axis. Adaptogens, such as Withania somnifera (ashwagandha), are commonly used in Ayurvedic medicine for stress relief and ameliorating HPA-axis dysfunction. The aim of this study was to support the role of a root and leaf water-extracted ashwagandha extract (WS) in stress reduction by confirming the lowest clinically validated dose for stress management (125 mg/day) in a dose-dependent clinical study in adults with self-reported high stress. An 8-week, randomized, double-blinded, placebo-controlled study to compare the effects of three different WS extract doses (125, 250 and 500 mg) was performed. A total of 131 adults were enrolled, and 98 were included in the final analysis. Attenuation of chronic stress was measured using the 14-item Perceived Stress Scale (PSS) and biochemical-related stress parameters. We have shown that aqueous WS extract (roots and leaves) safely reduces mild to moderate chronic stress at doses of 125 mg, 250 mg, and 500 mg/day for 8 weeks. Our findings demonstrate the stress-reduction capabilities of this well-characterized aqueous extract of WS (root and leaf) at the low dose of 125 mg/day, in a dose-dependent manner, via the modulation of the HPA axis. This study was registered with the Clinical Trials Registry-India (CTRI) with the registration number: CTRI/2019/11/022100.

Effects of Ashwagandha ( Withania somnifera) standardized root extract on physical endurance and VO 2max in healthy adults performing resistance training: An eight-week, prospective, randomized, double-blind, placebo-controlled study.

Ashwagandha is a well-known Ayurvedic herb used for youthful vigor and wellbeing. This study investigated the effects of 600 mg standardized root extract (>5% withanolides) of Ashwagandha ( Withania somnifera) on muscle size, strength and cardiorespiratory endurance following resistance training. In this eight-week, parallel-group, multicenter, randomized, double-blind, placebo-controlled clinical study, 80 healthy male and female participants aged 18-45 years, who engaged in regular physical activity were randomly allocated in a 1:1 ratio to receive Ashwagandha (AG, n=40) 300 mg capsules twice daily for eight weeks, or identical placebo (PB, n=40). Seven (3 AG, 4 PB) participants were excluded due to poor compliance. All participants conducted eight-week resistance training. Study outcomes included muscle strength (1RM bench press and leg extension), muscle size(circumference of arm, chest and upper thigh) and cardio-respiratory endurance(VO 2max) assessed at baseline and at eight weeks. Analysis of covariance (ANCOVA) was used to estimate adjusted differences based on sex, BMI and chest circumference at baseline. AG caused greater improvement in bench press (males: p = 0.0084; females: p = 0.0005), leg press (males: p = 0.0049; females: p = 0.018) and endurance (males: p <0.0001; females: p <0.0001) as compared to PB. Also, greater improvements in muscle girth for arm, chest and thigh were seen in both male and female participants with AG. No adverse events were reported in the study. Eight weeks of AG root extract supplementation along with resistance training is effective in improving muscle strength, growth and endurance in both male and female participants. AG root extract could be a safer, effective and low-cost alternative for athletes to improve muscle endurance.

Acid curd (Karish) cheese supplemented with ashwagandha and/or probiotics: Modulatory efficiency on induced behavioral and neurochemical changes in rats

Neurodegenerative disorder leads to a progressive memory loss that has only limited known medications. The use of ashwagandha, probiotics, or their combination may improve cholinergic activity, consequently providing therapeutic potency against amnesia and neuroplasticity disorders. We aimed to explore the modulatory benefits of ashwagandha extract and probiotics against induced behavioral and neurochemical retardations. &#x0D; Acid curd (Karish) cheese samples were supplemented with ashwagandha extract and/or probiotics and subjected to chemical, microbiological, rheological, sensorial, and biological investigations by standard techniques.&#x0D; The supplementation of Karish cheese with ashwagandha never deteriorated its chemical composition or rheological parameters. On the contrary, it exerted high antioxidant and phenolic potentials. Also, ashwagandha extract performed antimicrobial action against the tested pathogenic bacteria and showed better prebiotic effects with Lactobacillus plantarum. The biological study revealed that treating dementia-modeled rats with Karish cheese supplemented with ashwagandha and/or probiotics resulted in a detectable improvement in the behavioral and neurochemical measurements. However, the cheese supplemented with a formula of ashwagandha and probiotics had the greatest regenerating effect. &#x0D; The supplementation of Karish cheese with ashwagandha and/or probiotics exhibited a modulatory efficiency against experimentally induced behavioral and neurochemical disorders.

Therapeutic action of ashwagandha extract on apoptosis and cell proliferation in the heart of rat fetuses prenatally treated with clozapine

ABSTRACT An effective atypical antipsychotic medication for treating psychosis is clozapine, especially for patients who have failed to respond to other treatments. However, clozapine-induced cardiotoxicity has generated safety concerns as it may result in sudden mortality. In addition, there is relatively little information on the safety of clozapine during pregnancy. According to several earlier studies, Withania somnifera (ashwagandha) extract has a cardioprotective effect. Therefore, this study aimed to investigate the therapeutic potential of ashwagandha root extract on clozapine-induced cardiotoxicity in rat fetuses. Pregnant rats were administered clozapine (40 mg/kg bw) and/or ashwagandha extract (300 mg/kg bw.) from the sixth to fifteenth day of gestation. Clozapine-induced oxidative stress in developing hearts by decreasing superoxide dismutase and catalase activities and increasing the concentration of cardiac malondialdehyde. Moreover, there was a significant increase in the percentage of apoptotic cells and a decrease in the proliferative capacity of cardiomyocytes. Evidently, clozapine triggered severe pathological changes in fetal cardiac tissue. In conclusion, ashwagandha root extract can be used to improve the heart oxidative stress, apoptotic and proliferation rates and histopathological changes induced by clozapine in rat fetuses during gestation.

Study of Drug Targets Associated With Oncogenesis and Cancer Cell Survival and the Therapeutic Activity of Engineered Ashwagandha Extract Having Differential Withanolide Constitutions.

Ashwagandha (Withania somnifera) has gained worldwide popularity for a multitude of health benefits inclusive of cancer-preventive and curative effects. Despite numerous research data supporting the benefits of this wonder herb, the actual use of ashwagandha for cancer treatment in clinics is limited. The primary reason for this is the inconsistent therapeutic outcome due to highly variable composition and constitution of active ingredients in the plant extract impacting ashwagandha's pharmacology. We investigate here an engineered yield: an ashwagandha extract (Oncowithanib) that has a unique and fixed portion of active ingredients to achieve consistent and effective therapeutic activity. Using the MCF7 cell line, Oncowithanib was studied for its anti-neoplastic efficacy and drug targets associated with cell cycle regulation, translation machinery, and cell survival and apoptosis. Results demonstrate a dose-dependent decline in Oncowithanib-treated MCF7 cell viability and reduced colony-forming ability. Treated cells showed increased cell death as evidenced by enhancement of Caspase 3 enzyme activity and decreased expressions of cell proliferation markers such as Ki67 and Aurora Kinase A. Oncowithanib treatment was also found to be associated with expressional suppression of key cellular kinases such as RSK1, Akt1, and mTOR in MCF7 cells. Our findings indicate that Oncowithanib decreases MCF7 cell survival and propagation, and sheds light on common drug targets that might be good candidates for the development of cancer therapeutics. Further in-depth investigations are required to fully explore the potency and pharmacology of this novel extract. This study also highlights the importance of the standardization of herbal extracts to get consistent therapeutic activity for the disease indication.

Evaluation of the Effect of Ashwagandha (Withanaia somnifera) Extract on Survival Rate and Expression of P53 Gene in Ovarian Cancer (A2780 cell line)

Evaluation of the Effect of Ashwagandha (Withanaia somnifera) Extract on Survival Rate and Expression of P53 Gene in Ovarian Cancer (A2780 cell line)

Effects of Ashwagandha (Withania Somnifera) Supplementation on Body Composition and Blood Health Indices in Professional Wrestlers

Abstract Introduction. The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the effect of ashwagandha supplementation on the body composition, blood health and recovery indices, as well as the safety of ashwagandha supplementation in wrestling. Material and Methods. To investigate this, body composition (using dual energy X-ray absorptiometry; DEXA) and blood parameters as indicators of athletes’ health status (i.e., hematology, liver, kidney and muscle tissue function, lipid profile) were measured before and after 8-week supplementation with ashwagandha extract (600 mg/day) in professional national team wrestlers following an intensive training plan (as part of an annual training cycle). Results. At the end of the study, there was a significant increase in fat-free mass and muscle mass, with a significant decrease in fat mass (both in absolute and relative terms) in both ashwagandha and placebo groups (main effect of time, p &lt; 0.05). However, ashwagandha supplementation did not affect any of the body composition parameters (main effect of group or interaction of time and group, p &gt; 0.05). Moreover, intense wrestling training induced an increase in blood creatine kinase activity as an indicator of muscle tissue damage (main effect of time, p &lt; 0.05). Ashwagandha supplementation did not significantly affect any hematological or biochemical blood parameters (p &gt; 0.05 for main effect of group and interaction of time and group). However, the increase in creatine kinase activity during the study seemed to be more pronounced in the placebo group (post-hoc; p &lt; 0.05) than in the ashwagandha group (post-hoc; p &gt; 0.05). Conclusions. In conclusion, ashwagandha supplementation at 600 mg daily for 8 weeks is well tolerated and safe for professional wrestlers. This strategy does not appear to offer additional body composition benefits beyond the effect of intense wrestling training. On the other hand, our results indicate some potential for ashwagandha in improving muscle tissue recovery, which needs to be confirmed on a larger population of athletes.

Pharmacokinetics and bioequivalence of Withania somnifera (Ashwagandha) extracts – A double blind, crossover study in healthy adults

IntroductionWithania somnifera (WS) or ashwagandha is an adaptogenic plant used extensively in traditional medicines and as a food supplement. Despite a long history of use and numerous clinical trials, the human pharmacokinetics of withanolides, the active phytochemicals in WS extracts, have not been fully evaluated. This study evaluated the oral pharmacokinetics and bioequivalence of active withanolides in human plasma after administration of a single dose of two commercial ashwagandha extracts containing equal amounts of total withanolides. MethodsThis randomized, double-blind, single-dose crossover study of 16 healthy human volunteers evaluated the acute oral bioavailability of withanolides and the bioequivalence of two WS extracts, WS-35 and WS-2.5. WS-35 was standardized to total withanolides not less than 40% comprising not less than 35% withanolide glycosides and WS-2.5 was standardized to 2.5% withanolides. The clinical dosages were normalized to 185 mg of total withanolide in each extract at the bioequivalent dosages. The pharmacokinetic parameters of withanolide A, withanoside IV, withaferin A, and total withanolides were quantified in the blood plasma using a validated LC-MS/MS method. ResultsThe half-life, C-max, and mean residence time of the total withanolides were 5.18, 5.62 and 4.13 times significantly higher and had lower systemic clearance with WS-35 than with WS-2.5 extract. Considering the plasma AUC 0-inf of total withanolides per mg of each WS extract administered orally, WS-35 was 280.74 times more bioavailable than WS-2.5. ConclusionThe results of this study highlight the importance of withanolide glycosides in improving the pharmacokinetics of WS extracts. Owing to its superior pharmacokinetic profile, WS-35, with 35% withanolide glycosides, is a promising candidate for further studies on Withania somnifera. Clinical trial registrationCTRI/2020/10/028397 [registered on:13/10/2020] (Trial prospectively registered) http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=42149&EncHid=&userName=CTRI/2020/10/028397.

A validated green UPLC method for the quantification of synthetic pharmaceutical adulterants in the extract of the aphrodisiac herbal plant ashwagandha (Withania somnifera) and in spiked human plasma

In this work, an ultra-performance liquid chromatographic method was developed and subjected to bioanalytical method validation for screening the root extract of Ashwagandha. The method was also extended for simultaneous determination of Sildenafil, Vardenafil and Avanafil in plant root extract and in human plasma samples to detect the possible counterfeiting of the plant's pharmaceutical products with other synthetic drugs that might endanger the life of their consumers, particularly elderly people, and those with chronic diseases. The method was developed using BDS Hypersil TM C18 column (250 × 4.6 mm and 3 μm particle size) as a stationary phase and a mobile phase consisting of acidified water and acetonitrile in a gradient elution program with a flow rate of 1.00 mL min 1. In the plant extract, the proposed method was found to be linear in the range 1.00–200.0 μg mL−1 for the Vardenafil and Avanafil and 5.00–200.0 μg mL−1 for Sildenafil with a recovery percentage in range of 98.18–101.07 % for the three drugs. Intra-day and inter-day precision ranges were 0.088–1.219 and 0.151–1.313, respectively. The limit of detection and the limit of quantification for Vardenafil and Avanafil were 0.166 μg mL−1 and 0.500 μg mL−1, respectively. Whereas, for Sildenafil 0.333 μg mL−1 and 1.000 μg mL−1. The ICH validation parameters were also demonstrated. Bioanalytical method validation was established following US-FDA recommendations and the method showed good linearity in the range 1.00–200.00 μg mL −1 for Vardenafil and Avanafil, and 5.00–200.00 μg mL −1 for Sildenafil. The results revealed high accuracy with % recovery ranging from 91.05 to 98.91 % for the three drugs. The intra-day and inter-day precision were also conducted, in terms of % relative standard deviation, and ranged from 0.119 to 4.037 % and from 0.223 to 5.062 %, respectively. Furthermore, other validation parameters were evaluated including extraction recovery and stability of the analytes throughout samples preparation and storage for both short- and long-term. The method greenness was evaluated using NEMI, GAPI, AGREE and analytical eco-scale.

Mucoadhesive Chitosan-Coated PLGA Nanoparticles of Ashwagandha Extract for Colon-Targeted Delivery

Mucoadhesive Chitosan-Coated PLGA Nanoparticles of Ashwagandha Extract for Colon-Targeted Delivery

Study of Drug Target Identification and Associated Molecular Mechanisms for the Therapeutic Activity and Hair Follicle Induction of Two Ashwagandha Extracts Having Differential Withanolide Constitutions.

Ashwagandha extracts play a significant role in traditional Indian medicine to help treat a wide range of disorders from amnesia, erectile dysfunction, neurodegenerative and cardiovascular diseases, cancer, stress, anxiety, and many more. Ashwagandha root is enriched with bioactive plant metabolites of which withanolides are the most important ones. The concentration and constitution of withanolides primarily determine ashwagandha's potency and pharmacology. Various factors modulate the withanolide constitution in the plant-derived extracts, rendering inconsistent therapeutic efficacy. Standardisation of the extraction protocol and a better understanding of the pharmacology mechanism of different extracts with varied withanolide constitutions is therefore critical for developing reliable, repeatable, and effective ashwagandha-based treatment. Here, we work toward defining indication mechanisms for two varieties of ashwagandha extract-ASHWITH (ASH-Ext1) and Regenolide (ASH-Ext2)-with different proprietary withanolide proportions. ASH-Ext1 was studied for antioxidant signaling modulation using HEK293, HeLa, and A549 cells, and ASH-Ext2 was studied for subcellular drug targets associated with the reactivation and longevity of human hair follicles, using primary human hair follicle dermal papilla cells (HFDPCs). Study findings support the antioxidant activity and Nrf2 signaling modulation by ASH-Ext1 in various cell models. Of note, ASH-Ext2 was found to increase β-catenin and telomerase reverse transcriptase (TERT) protein expression levels in HFDPCs. The results of drug target modulation show us that the withanolide constitution associated with different extraction protocols influences the pharmacological potential of the extract significantly and points to the value of standardisation not only of total withanolide content but also of internal withanolide proportions.

Electrospun polyvinyl alcohol/Withania somnifera extract nanofibers incorporating tadalafil-loaded nanoparticles for diabetic ulcers.

Background: Impaired inflammation and vascularization are common reasons for delayed diabetic wound healing. Nanoparticles (NPs)-in-nanofiberscomposites can manage diabetic wounds. A multifunctional scaffold was developed based on tadalafil (TDF)-loaded NPs incorporated into polyvinyl alcohol/Withania somnifera extract nanofibers. Materials & methods: TDF-loaded NPs were prepared and fully characterized in terms of their physicochemical properties. Extract of ashwagandha was prepared and a blend composed of TDF-loaded NPs, herbal extract and polyvinyl alcohol was used to prepare the whole composite. Results: The whole composite exhibited improved wound closure in a diabetic rat model in terms of reduced inflammation and enhanced angiogenesis. Conclusion: Results suggest that this multifunctional composite could serve as a promising diabetic wound dressing.

Ashwagandha- Withania somnifera (L.) Dunal as a multipotent neuroprotective remedy for genetically induced motor dysfunction and cellular toxicity in human neurodegenerative disease models of Drosophila

Ethnopharmacological relevanceAshwagandha-Withania somnifera (L.) Dunal, well known for its multipotent therapeutic properties has been used in Ayurveda for 3000 years. The plant with more than 50 active phytoconstituents is recognised for its anti-cancerous, anti-diabetic, anti-inflammatory, anti-microbial, and neurotherapeutic properties demonstrated in in vitro studies and chemically induced rodent models. Genetically targeted Parkinson’s, Alzheimer’s and other neurodegenerative disease models have been created in Drosophila and have been used to get mechanistic insight into the in vivo cellular events, and genetic pathways that underlie respective neurodegenerative condition. But hitherto, there aren’t enough attempts made to capitalize the genetic potential of these disease models to validate the therapeutic efficacy of different reagents used in traditional medicine, in the context of specific disease-causing genetic mutations. Aim of the studyDrugs discovered using in vitro platforms might fail in several instances of clinical trials because of the genetic heterogeneity and variability in the physiological context found among the patients. Drosophila by virtue of its genetically regulated experimental potential forms an ideal in vivo model to validate the candidate reagents discovered in in vitro screens for their efficacy under specific genetic situations. Here we have used genetically induced α-synucleinopathy and tauopathy transgenic fly models to study the efficacy of Ashwagandha treatment, assessing cellular and behavioural parameters. MethodsWe have expressed the disease-causing human gene mutations in specific cell types of Drosophila using GAL4/UAS targeted expression system to create disease models. Human α-synuclein mutant (A30P) was expressed in dopaminergic neurons using Ddc-GAL4 driver strain to induce dopaminergic neurodegeneration and assayed for motor dysfunction. Human TauE14, mutant protein was expressed in photoreceptor neurons using GMR-GAL4 driver to induce photoreceptor degeneration. Microtubular destability and mitotic arrest in the dividing photoreceptor precursor cells were studied using αPH3 antibody. Lysosomal dysregulation caused necrotic black spots were induced by TauE14 with GMR-GAL4 driver, in a white mutant background. These flies mimicking neurodegenerative conditions were supplemented with different concentrations of Ashwagandha aqueous root extract mixed with regular fly food. The treated flies were analysed for cellular and behaviour parameters. ResultsLifespan assay shows that, Ashwagandha-root extract imparts an extended lifespan in male Drosophila flies which are intrinsically less stress resistant. Motor dysfunction caused due to human α-synuclein mutant protein expressed in dopaminergic neurons is greatly brought down. Further, Ashwagandha extract treatment significantly reduces TauE14 induced microtubular destability, mitotic arrest and neuronal death in photoreceptor neurons. Our experiment with tauopathy model in white mutant background exemplify that, Ashwagandha-root extract treatment can bring down lysosomal dysregulation induced necrosis of photoreceptor neurons. ConclusionWe have carried out a multifaceted study which elucidates that Ashwagandha can serve as a comprehensive, phytotherapeutic formulation to combat neurodegeneration, targeting multiple causative genetically defective conditions.