Clinical safety and tolerability evaluation of Withania somnifera (L.) Dunal (Ashwagandha) root extract in healthy human volunteers.

BACKGROUND: Withania somnifera (L.) Dunal, known as Ashwagandha, is an adaptogen with significant importance in Ayurveda for its potential health benefits in strength ('balavardhan') and muscle growth ('mamsavardhan'). Despite numerous studies on its efficacy, limited research is reported on its clinical safety and tolerability in healthy individuals. OBJECTIVE: This research evaluated the tolerability and safety of standardized Withania somnifera root extract (WSE) capsules (AgeVel®/Witholytin®) at 1000 mg/day dose upon oral administration in healthy male participants. METHOD: A non-randomized, open-label, single-treatment clinical study included eighteen healthy male participants aged 18 to 60. The participants were administered a dose of 500 mg of the WSE capsules twice daily for four weeks. Each capsule contained not less than 7.50 mg of total withanolides. The study evaluated various indicators in a cohort of healthy participants throughout the trial, including vital signs, organ function tests, urine analysis, X-ray and ECG, cardiorespiratory endurance, body fat percentage, lean body weight, adverse events profile, and tolerability of the WSE capsules. RESULTS: The participant's physical, hematological, and biochemical characteristics were normal, and no significant alterations or irregularities were observed in safety metrics like liver, kidney, and thyroid functions after administering AgeVel®/Witholytin®. CONCLUSION: This study found that healthy male participants could consume a standardized WSE at a daily dosage of 1000 mg for four weeks without any adverse effects. Future research should focus on long-term safety assessments in male and female participants.

Molecular mechanisms of Asparagus racemosus willd. and Withania somnifera (L.) Dunal as chemotherapeutic adjuvants for breast cancer treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Despite various treatment modalities, the progression and metastasis of breast cancer (BC) are grave concerns due to the alarming disease-free survival rate (DFS) and overall survival rate (OS) of affected patients. Over the years, many antibiotics, synthetic compounds, medicinal plant isolates and polyherbal combinations have been used as adjuvants in therapy for the management of primary and secondary tumors. Paclitaxel (PTX)-based chemotherapy for breast cancer causes multiple adverse side effects in patients. Withania somnifera (L.) Dunal (WS) and Asparagus racemosus Willd. (AR) as Ayurveda-inspired plant-based adjuvants were investigated for their anticancer effects on MDA-MB-231 and 4T1 cells in mouse model systems. AIM OF THE STUDY: This study focused on evaluating the adjuvant properties of WS and AR plant extracts with PTX and their effectiveness over PTX alone in terms of tumor inhibition. MATERIALS AND METHODS: The effects of WS and AR on DNA double-strand breaks (DSBs), senescence induction and mitochondrial functions were evaluated in BC cells in vitro. The potential for cancer stem cell (CSC) inhibition was evaluated via mammosphere formation assays and CD44/CD24 immunostaining. In vivo tumor growth studies were conducted in athymic BALB/c mice for MDA-MB-231 cells and in BALB/c mice for 4T1 cells. RESULTS: Induction of senescence was evident due to DSBs induced by the WS and AR extracts. Mammosphere formation and CD44/CD24 CSC markers were reduced after treatment with WS, AR or the combination of both in MCF-7 cells. WS or AR inhibited epithelial-to-mesenchymal transition (EMT). In vivo studies demonstrated that tumor growth inhibition was more pronounced in the treated group than in the PTX alone group and the untreated control group. CONCLUSION: Our study showed that the use of WS or AR plant hydroalcoholic extracts in combination with paclitaxel (PTX) has better effects on sensitivity and efficacy than PTX alone, as demonstrated in in vitro BC cells and mouse models with BC cell grafts. Hence, scheduling adjuvant therapy with WS or AR alone or combined with PTX can be advantageous for the management of triple-negative BC (TNBC). Further studies are warranted in human clinical conditions to ascertain the efficacy of these treatments.

Withania somnifera (L.) Dunal, a Potential Source of Phytochemicals for Treating Neurodegenerative Diseases: A Systematic Review.

Withania somnifera (L.) Dunal is a medicinal plant belonging to the traditional Indian medical system, showing various therapeutic effects such as anti-cancer, anti-inflammatory, anti-microbial, anti-diabetic, and hepatoprotective activity. Of great interest is W. somnifera's potential beneficial effect against neurodegenerative diseases, since the authorized medicinal treatments can only delay disease progression and provide symptomatic relief and are not without side effects. A systematic search of PubMed and Scopus databases was performed to identify preclinical and clinical studies focusing on the applications of W. somnifera in preventing neurodegenerative diseases. Only English articles and those containing the keywords (Withania somnifera AND "neurodegenerative diseases", "neuroprotective effects", "Huntington", "Parkinson", "Alzheimer", "Amyotrophic Lateral Sclerosis", "neurological disorders") in the title or abstract were considered. Reviews, editorials, letters, meta-analyses, conference papers, short surveys, and book chapters were not considered. Selected articles were grouped by pathologies and summarized, considering the mechanism of action. The quality assessment and the risk of bias were performed using the Cochrane Handbook for Systematic Reviews of Interventions checklist. This review uses a systematic approach to summarize the results from 60 investigations to highlight the potential role of W. somnifera and its specialized metabolites in treating or preventing neurodegenerative diseases.

In Vitro Inhibition of Colorectal Cancer Gene Targets by Withania somnifera L. Methanolic Extracts: A Focus on Specific Genome Regulation.

An approach that shows promise for quickening the evolution of innovative anticancer drugs is the assessment of natural biomass sources. Our study sought to assess the effect of W. somnifera L. (WS) methanolic root and stem extracts on the expression of five targeted genes (cyclooxygenase-2, caspase-9, 5-Lipoxygenase, B-cell lymphoma-extra-large, and B-cell lymphoma 2) in colon cancer cell lines (Caco-2 cell lines). Plant extracts were prepared for bioassay by dissolving them in dimethyl sulfoxide. Caco-2 cell lines were exposed to various concentrations of plant extracts, followed by RNA extraction for analysis. By explicitly relating phytoconstituents of WS to the dose-dependent overexpression of caspase-9 genes and the inhibition of cyclooxygenase-2, 5-Lipoxygenase, B-cell lymphoma-extra-large, and B-cell lymphoma 2 genes, our novel findings characterize WS as a promising natural inhibitor of colorectal cancer (CRC) growth. Nonetheless, we recommend additional in vitro research to verify the current findings. With significant clinical benefits hypothesized, we offer WS methanolic root and stem extracts as potential organic antagonists for colorectal carcinogenesis and suggest further in vivo and clinical investigations, following successful in vitro trials. We recommend more investigation into the specific phytoconstituents in WS that contribute to the regulatory mechanisms that inhibit the growth of colon cancer cells.

Ayurvedic Management of Presbycusis (Project TOPMAC): Protocol for an Exploratory Randomized Controlled Trial.

BACKGROUND: Presbycusis is characterized by sensorineural hearing loss in both ears at high frequencies, which affects more than half of the older adults by the age of 75 years and is often accompanied by tinnitus and cognitive deterioration. Unfortunately, there are no treatments available to restore hearing loss. Treatment mainly focuses on improving the quality of life and communication with hearing aids. Traditional medicine like Ayurveda also explains ailments of a similar nature as Badhirya and advises using drugs with antiaging and neuroprotective activity for treatment. In Ayurveda, Badhirya and Karnanada (senile deafness with tinnitus) are due to vitiation of Vata Dosha. Treatments such as topical oil pooling (Karnapurana) are usually advised to counter Vata, improve hearing capacity, and reduce tinnitus. Kshirabala Taila, a medicated oil formulation prepared with Sida cordifolia Linnaeus, is one of the most preferred oils for topical oil pooling in such conditions, as it has a definitive indication for sensory dysfunctions. Drugs like Withania somnifera (L.) Dunal (Ashwagandha) are also used, as they ameliorate neurodegeneration and help to improve cognitive dysfunction. OBJECTIVE: We propose an exploratory randomized controlled trial study for evaluating the efficacy of TOPMAC (Topical Oil Pooling with Kshirabala Taila and Supplementation of Ashwagandha Churna) in tinnitus suppression and hearing and cognitive function protection in patients aged 60-75 years with mild to moderate presbycusis. METHODS: A parallel, 2-group, exploratory randomized controlled trial will be conducted in an Indian Ayurvedic research center at its outpatient service. Participants (N=60) with mild to moderate presbycusis will be recruited by screening. Participants will be randomized (computer-generated 1:1) to receive either basic treatment and health education (BTHE) or BTHE+TOPMAC for 24 weeks. The primary objective is to compare the efficacy of TOPMAC with that of BTHE in the protection of hearing function. The secondary objective is to compare the efficacy of TOPMAC with that of BTHE in tinnitus suppression and cognitive function protection. RESULTS: This project was funded in January 2023. The institutional ethics committees at National Ayurveda Research Institute for Panchakarma (3/1/2020/NARIP/Tech/2036) and Institute for Communicative and Cognitive Neuro Sciences (IEC006) approved this study. The first patient was enrolled in September 2023; 22 participants were enrolled as of August 2024. The data analysis is yet to start, and the results are expected to be published by January 2025. CONCLUSIONS: If this exploratory trial is proven effective, it will steer the setting of a definitive randomized controlled trial to test whether the TOPMAC intervention can be incorporated as a cost-effective integrative approach for managing presbycusis. The Indian government has already launched a National Program for Prevention and Control of Deafness to benefit the deaf population. TOPMAC may later be considered for integration with the national program. TRIAL REGISTRATION: Clinical Trials Registry India CTRI/2023/04/051485; https://tinyurl.com/2h2hry3n. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55089.

Copper-stress induced alterations in protein profile and antioxidant enzymes activities in the in vitro grown Withania somnifera L.

Withania somnifera L. seedlings were grown in half-strength MS (Murashige and Skoog) basal medium for 4 weeks and then transferred to full-strength MS liquid medium for 3 weeks. The sustainable plants were subcultured in the same medium but with different concentrations (0, 25, 50, 100 and 200 µM) of Cu for 7 and 14 days. The growth parameters (root length, shoot length, leaf length and total number of leaves per plant) showed a declining trend in the treated plants in a concentration dependant manner. Roots and leaves were analyzed for protein profiling and antioxidant enzymes [catalase (CAT, EC 1.11.1.6), superoxide dismutase (SOD, EC 1.15.1.1) and guaiacol peroxidase (GPX, EC 1.11.1.7)]. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of crude protein extracts showed the appearance of some new proteins due to Cu treatment. In plant samples grown with 25 and 50 µM of Cu, a rapid increase in antioxidant activities were noticed but at higher concentration (100 and 200 µM) the activities declined. Isoforms of CAT, SOD and GPX were separated using non-denaturing polyacrylamide gel electrophoresis and concentration specific new isoforms were noticed during the study. Isoforms of the antioxidant enzymes synthesized due to Cu stress may be used as biomarkers for other species grown under metal stress.

An updated review on phytochemistry and molecular targets of Withania somnifera (L.) Dunal (Ashwagandha).

Withania somnifera (L.) Dunal belongs to the nightshade family Solanaceae and is commonly known as Ashwagandha. It is pharmacologically a significant medicinal plant of the Indian sub-continent, used in Ayurvedic and indigenous systems of medicine for more than 3,000 years. It is a rich reservoir of pharmaceutically bioactive constituents known as withanolides (a group of 300 naturally occurring C-28 steroidal lactones with an ergostane-based skeleton). Most of the biological activities of W. somnifera have been attributed to two key withanolides, namely, withaferin-A and withanolide-D. In addition, bioactive constituents such as withanosides, sitoindosides, steroidal lactones, and alkaloids are also present with a broad spectrum of therapeutic potential. Several research groups worldwide have discovered various molecular targets of W. somnifera, such as inhibiting the activation of nuclear factor kappa-B and promoting apoptosis of cancer cells. It also enhances dopaminergic D2 receptor activity (relief in Parkinson's disease). The active principles such as sitoindosides VII-X and withaferin-A possess free radical properties. Withanolide-D increases the radio sensitivity of human cancer cells via inhibiting deoxyribonucleic acid (DNA) damage to non-homologous end-joining repair (NHEJ) pathways. Withanolide-V may serve as a potential inhibitor against the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to combat COVID. The molecular docking studies revealed that the withanolide-A inhibits acetyl-cholinesterase in the brain, which could be a potential drug to treat Alzheimer's disease. Besides, withanolide-A reduces the expression of the N-methyl-D-aspartate (NMDA) receptor, which is responsible for memory loss in epileptic rats. This review demonstrates that W. somnifera is a rich source of withanolides and other bioactive constituents, which can be used as a safe drug for various chronic diseases due to the minimal side effects in various pre-clinical studies. These results are interesting and signify that more clinical trials should be conducted to prove the efficacy and other potential therapeutic effects in human settings.

Medicinal Characteristics of Withania somnifera L. in Colorectal Cancer Management.

Research into tumorigenic pathways can aid in the development of more efficient cancer therapies and provide insight into the physiological regulatory mechanisms employed by rapidly proliferating cancer cells. Due to the severe side effects of cancer chemotherapeutic medications, plant chemicals and their analogues are now explored more frequently for the treatment and prevention of colorectal cancer (CRC), opening the stage for new phytotherapeutic strategies that are considered effective and safe substitutes. Our study aimed to evaluate the medicinal properties of Withania somnifera L. and its safety applications in CRC management. Important databases were rigorously searched for relevant literature, and only 82 full-text publications matched the inclusion requirements from a massive collection of 10,002 titles and abstracts. W. somnifera L. contains a high concentration of active plant-based compounds. The pharmacological activity of the plant from our study has been demonstrated to exert antiproliferation, upregulation of apoptosis, decrease in oxidative stress, downregulation of cyclooxygenase-2 (COX-2), induction of targeted cytotoxic effects on cancerous cells, and exertion of both antiangiogenesis and antimigratory effects. We advise further research before recommending W. somnifera L. for clinical use to identify the optimal concentrations required to elicit beneficial effects in CRC management in humans, singly or in combination.

Withania somnifera (L.) Dunal - Modern perspectives of an ancient Rasayana from Ayurveda.

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal, commonly known as Ashwagandha, is an important medicinal plant that has been used in Ayurvedic and indigenous medicine for more than 3000 years. According to Charaka Samhita, Susruta Samhita and other ancient texts, Ashwagandha is known as Balya (increases strength), Brusya (sexual performance enhancer), vajikari (spermatogenic), Kamarupini (libido-enhancing), Pustida (nourishing). AIM OF THE REVIEW: This review article documented and critically assessed W. somnifera regarding its ethnopharmacology, traditional use, botanical description, phytochemicals present, pharmacological activities, clinical trials, and marketed formulations. MATERIALS AND METHODS: The sources of information used in the study are traditional Ayurvedic books like Charaka Samhita, Susruta Samhita, Astanga Hridaya etc, government reports, dissertations, books, research articles and databases like Science-Direct, SciFinder, Web of Science, PubMed, Wiley Online Library, and ACS Publications on Ashwagandha and Withania somnifera (L.) Dunal. RESULTS: Traditional uses of Ashwagandha in Ayurveda are very prominent in several texts where formulations with various dosage forms have been mentioned in Charaka Samhita, Susruta Samhita, Astanga Hridaya, different nighantus etc. The drugs were identified based on their composition containing Ashwagandha as one of the major ingredients and their medicinal uses. Phytochemical studies on W. somnifera revealed the presence of important chemical constituents such as flavonoids, phenolic acids, alkaloids, saponins, tannins, and withanolides. The phytochemicals showed various pharmacological activities like anti-cancer, immunomodulatory, cardioprotective, neuroprotective, anti-aging, anti-stress/adaptogenic and anti-diabetic. Various clinical trials show that the plant extract and its bioactive compounds are used in the prevention and treatment of many diseases, such as arthritis, impotence, amnesia, anxiety, cancer, neurodegenerative and cardiovascular diseases, and others. CONCLUSIONS: Pharmacological data reviewed here revealed that W. somnifera is a potential source for the treatment of a wide range of diseases especially anxiety and other CNS disorders. From its ancient use to its modern application it has been proven to be non-toxic and effective clinically for human health and wellness. W. somnifera based herbal formulation has been marketed in the form of supplement, extract, capsule, powder etc. This review will be helpful to correlate the mechanism of action with the phytochemical profile of this well-known plant from Ayurveda.

Standardized root extract of Withania somnifera and Withanolide A exert moderate vasorelaxant effect in the rat aortic rings by enhancing nitric oxide generation.

ETHNO-PHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal, commonly known as Ashwagandha, belongs to the family Solanaceae. In Ayurveda, Ashwagandha has been defined as one of the most important herb and is considered to be the best adaptogen. It is also an excellent rejuvenator, a general health tonic and cure for various disorders such as cerebrovascular, insomnia, asthma, ulcers, etc. Steroidal lactones (Withanolides: Withanolide A, Withaferin A, Withanolide D, Withanone, etc) isolated from this plant, possess promising medicinal properties such as anti-inflammatory, immune-stimulatory etc. Standardized root extract of the plant NMITLI-118R (NM) was prepared at CSIR-CIMAP, and was investigated for various biological activities at CSIR-CDRI. Among the notable medicinal properties, NM exhibited excellent neuroprotective activity in the middle cerebral artery occlusion (MCAO) rat model. AIM OF THE STUDY: Endothelial dysfunction is the primary event in the cerebrovascular or cardiovascular disorders, present study was thus undertaken to evaluate vasoprotective potential of NM and its biomarker compound Withanolide A (WA) using rat aortic rings and EA.hy926 endothelial cells. MATERIAL AND METHODS: Transverse aortic rings of 10 weeks old Wistar rats were used to evaluate effect of NM and WA on the vasoreactivity. While, mechanism of NM and WA mediated vasorelaxant was investigated in Ea.hy926 cell line by measuring NO generation, nitrite content, Serine 1177 phosphorylation of eNOS, reduced/oxidized biopterin levels and expression of endothelial nitric oxide synthase (eNOS) mRNA and protein. RESULTS: Fingerprinting of NM using HPLC identified presence of WA in the extract. NM as well as WA exerted moderate vasorelaxant effect in the endothelium intact rat aortic rings which was lesser than acetylcholine (ACh). NM and WA augmented ACh induced relaxation in the rat aortic rings. NM and WA dependent vasorelaxation was blocked by N-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4] oxadiazolo [4,3,-a]quinoxalin-1-one (ODQ), indicating role of NO/cGMP. Further Ea.hy926 cells treated with NM and WA showed accumulation of nitrite content, enhanced NO levels, eNOS expression and eNOS phosphorylation (Serine 1177). CONCLUSION: Altogether NM and WA dependent improvement in the NO availability seems to be mediated by the enhanced eNOS phosphorylation. WA, seems to be one of the active constituent of NM, and presence of other vasoactive substances cannot be ruled out. The data obtained imply that the vasorelaxant property of NM is beneficial for its neuroprotective potential.

Effect of Withania somnifera (L.) Dunal aqueous root extract on reinstatement using conditioned place preference and brain GABA and dopamine levels in alcohol dependent animals.

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal (WS), a known'Rasayana' (rejuvenating agent) as per Ayurveda is prescribed to promote health, to increase longevity and to hasten recovery in disease convalescent stages. WS has demonstrated protective effect on alcohol dependence and withdrawal anxiety in previous experimental studies. AIM OF THE STUDY: To evaluate effect of WS on conditioned place behavioral paradigm (model of relapse) and on GABA and dopamine levels in critical brain areas in alcohol dependent animals. METHODOLOGY: Following Animal Ethics Committee permission, the mice (n = 24) were divided into the following study groups for experiment 1: 1 -distilled water (vehicle control), 2 -WS and 3 -Naltrexone. They were conditioned on conditioned place preference (CPP) using alcohol (2 gm/kg)/saline (1 ml) administered intraperitoneally for 8 days. WS and Naltrexone were administered during the period of extinction (6-8 days). Effect of WS (650 mg/kg) on reinstating behaviour of mice (time spent in alcohol paired compartment) primed with alcohol injection was noted. In experiment 2, effect of WS (450 mg/kg/) on GABA and dopamine levels in the midbrain, striatum and cortex (ng/gm) were measured in alcohol dependent rats (n = 24) following the first phase of standardisation assay (n = 36). The rats were made alcohol dependent for 15 days (intermittent access model) and WS was administered concurrently. GABA and dopamine levels were measured on Day 16. RESULTS: WS group showed decrease in time spent in alcohol paired compartment alike Naltrexone and it differed significantly compared to the distilled water control group (p < 0.05) Alcohol-dependent rats showed significant decrease in GABA and increase in dopamine levels vs distilled water in the midbrain, striatum and cortex. WS and Naltrexone administration showed rise in GABA and fall in dopamine in all the isolated brain parts in the respective groups (p < 0.05 vs alcohol treated group). CONCLUSION: Withania somnifera protected animals from relapse and showed beneficial effects on the brain neurotransmitters involved in alcohol dependence. The study provides substantial evidence for its potential application in alcohol use disorder.

Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial.

BACKGROUND: Subclinical hypothyroidism, a thyroid disorder without obvious symptoms of thyroid deficiency, occurs in 3%-8% of the global population. Ashwagandha [Withania somnifera (L.) Dunal], a traditional medicine in Ayurveda, is often prescribed for thyroid dysfunctions. OBJECTIVE: This pilot study was designed to evaluate the efficacy and safety of ashwagandha root extract in subclinical hypothyroid patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective, randomized, double-blind, single-center placebo-controlled study was performed at Sudbhawana Hospital, Varanasi, India between May 2016 and September 2016. Fifty subjects with elevated serum thyroid stimulating hormone (TSH) levels (4.5-10 µIU/L) aged between 18 and 50 were randomized in either treatment (n = 25) or placebo (n = 25) groups for an 8-week treatment period. INTERVENTIONS: Ashwagandha root extract (600 mg daily) or starch as placebo. Efficacy Variables: Serum TSH, serum triiodothyronine (T3), and thyroxine (T4) levels. RESULTS: A total of four subjects (two from each group) withdrew their consent before the second visit. Eight weeks of treatment with ashwagandha improved serum TSH (p < 0.001), T3 (p = 0.0031), and T4 (p = 0.0096) levels significantly compared to placebo. Ashwagandha treatment effectively normalized the serum thyroid indices during the 8-week treatment period in a significant manner (time-effects: TSH [p < 0.001], T3 [p < 0.001], and T4 [p < 0.001]). Four subjects (8%) (ashwagandha: 1[4%]; Placebo: 3[12%]) out of 50 reported few mild and temporary adverse effects during this study. CONCLUSION: Treatment with ashwagandha may be beneficial for normalizing thyroid indices in subclinical hypothyroid patients.

Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions.

OBJECTIVES: Cognitive decline is often associated with the aging process. Ashwagandha (Withania somnifera (L.) Dunal) has long been used in the traditional Ayurvedic system of medicine to enhance memory and improve cognition. AIM: This pilot study was designed to evaluate the efficacy and safety of ashwagandha (Withania somnifera (L.) Dunal) in improving memory and cognitive functioning in adults with mild cognitive impairment (MCI). METHODS: A prospective, randomized, double-blind, placebo-controlled study was conducted in 50 adults. Subjects were treated with either ashwagandha-root extract (300 mg twice daily) or placebo for eight weeks. RESULTS: After eight weeks of study, the ashwagandha treatment group demonstrated significant improvements compared with the placebo group in both immediate and general memory, as evidenced by Wechsler Memory Scale III subtest scores for logical memory I (p = 0.007), verbal paired associates I (p = 0.042), faces I (p = 0.020), family pictures I (p = 0.006), logical memory II (p = 0.006), verbal paired associates II (p = 0.031), faces II (p = 0.014), and family pictures II (p = 0.006). The treatment group also demonstrated significantly greater improvement in executive function, sustained attention, and information-processing speed as indicated by scores on the Eriksen Flanker task (p = 0.002), Wisconsin Card Sort test (p = 0.014), Trail-Making test part A (p = 0.006), and the Mackworth Clock test (p = 0.009). CONCLUSIONS: Ashwagandha may be effective in enhancing both immediate and general memory in people with MCI as well as improving executive function, attention, and information processing speed.