Adaptogens

An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract

Adrian L. Lopresti, Stephen J. Smith, Hakeemudin Malvi +1 more · Medicine · 2019 · 208 citations

BACKGROUND: Ashwagandha (Withania somnifera (L.) Dunal) is a herb traditionally used to reduce stress and enhance wellbeing. The aim of this study was to investigate its anxiolytic effects on adults with self-reported high stress and to examine potential mechanisms associated with its therapeutic effects. METHODS: In this 60-day, randomized, double-blind, placebo-controlled study the stress-relieving and pharmacological activity of an ashwagandha extract was investigated in stressed, healthy adults. Sixty adults were randomly allocated to take either a placebo or 240 mg of a standardized ashwagandha extract (Shoden) once daily. Outcomes were measured using the Hamilton Anxiety Rating Scale (HAM-A), Depression, Anxiety, and Stress Scale -21 (DASS-21), and hormonal changes in cortisol, dehydroepiandrosterone-sulphate (DHEA-S), and testosterone. RESULTS: All participants completed the trial with no adverse events reported. In comparison with the placebo, ashwagandha supplementation was associated with a statistically significant reduction in the HAM-A (P = .040) and a near-significant reduction in the DASS-21 (P = .096). Ashwagandha intake was also associated with greater reductions in morning cortisol (P < .001), and DHEA-S (P = .004) compared with the placebo. Testosterone levels increased in males (P = .038) but not females (P = .989) over time, although this change was not statistically significant compared with the placebo (P = .158). CONCLUSIONS: These findings suggest that ashwagandha's stress-relieving effects may occur via its moderating effect on the hypothalamus-pituitary-adrenal axis. However, further investigation utilizing larger sample sizes, diverse clinical and cultural populations, and varying treatment dosages are needed to substantiate these findings. TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI registration number: CTRI/2017/08/009449; date of registration 22/08/2017).

Targeting metabolic disorders by natural products

Ozra Tabatabaei‐Malazy, Bagher Larijani, Mohammad Abdollahı · Journal of Diabetes & Metabolic Disorders · 2015 · 132 citations

The most prevalent metabolic disorders are diabetes mellitus, obesity, dyslipidemia, osteoporosis and metabolic syndrome, which are developed when normal metabolic processes are disturbed. The most common pathophysiologies of the above disorders are oxidative stress, Nrf2 pathways, epigenetic, and change in miRNA expression. There is a challenge in the prevention and treatment of metabolic disorders due to severe adverse effects of some synthetic drugs, their high cost, lack of safety and poverty in some conditions, and insufficient accessibility for the general population in the world. With increasing interest in shifting from synthetic drugs to phytotherapy as an alternative treatment, there is still a gap in scientific evidences of plant-derived therapeutic benefits. One reason may be slow rate of translation of animal studies' findings into human clinical trials. Since metabolic disorders are multifactorial, it seems that poly-herbal medications, or drug-herbal combination are needed for their treatment. However, further researches to determine the most effective plant-derived metabolites, and their cellular mechanism in order to set priorities for well-designed animal and clinical trials, and also more studies with strong scientific evidences such as systematic review and meta-analysis of controlled studies are needed.

Ginkgo biloba: A Leaf of Hope in the Fight against Alzheimer’s Dementia: Clinical Trial Systematic Review

Guilherme Lopes de Oliveira Pagotto, Livia Maria Oliveira dos Santos, Najwa Osman +10 more · Antioxidants · 2024 · 32 citations

Alzheimer’s disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords—GB in AD and dementia—yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show that Ginkgo biloba has promising potential for the treatment of these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

Efficacy and Safety of Ashwagandha Root Extract on Cognitive Functions in Healthy, Stressed Adults: A Randomized, Double-Blind, Placebo-Controlled Study

Gopukumar Kumarpillai, Shefali Thanawala, Somepalli Venkateswarlu +3 more · Evidence-based Complementary and Alternative Medicine · 2021 · 88 citations

Background. The global prevalence of stress is increasing. Stress adversely affects cognitive ability, sleep quality, and overall psychological well-being. Ashwagandha (Withania somnifera (L.) Dunal), an essential medicine in Ayurveda, is reportedly beneficial in reducing stress and improving memory. This double-blind, randomized, placebo-controlled clinical study evaluated the effect of Ashwagandha root extract sustained-release capsule 300 mg (Prolanza™; hereafter Ashwagandha SR) on cognitive functions, stress levels, sleep quality, overall well-being, and safety in stressed subjects. Methods. Subjects (130 healthy cognitively sound adults [20–55 years, body mass index:18–29 kg/m2]) having a Perceived Stress Scale (PSS) score of 14–24 were randomized to receive either Ashwagandha SR or placebo. Subjects took one capsule of Ashwagandha SR or placebo daily for 90 consecutive days. This study was registered on Clinical Trials Registry-India (CTRI) on 13/11/2019 [number: CTRI/2019/11/021990]. The primary endpoint was the change in cognitive function as measured by CANTAB from baseline to the end of the study period (90 ± 7 days). The secondary outcomes included the change in PSS-10 score, serum cortisol level (9–11 am), the OHQ score, the PSQI, and serum BDNF levels. Results. Only 125 completed the study and were evaluated. The Cambridge Neuropsychological Test Automated Battery (CANTAB) reported significantly improved recall memory, and the total error rate in recalling patterns significantly decreased at visit 4 in the Ashwagandha SR group vs. the placebo group (first attempt memory score:12.9 ± 6.7 vs. 10.1 ± 6.3; total errors:17.5 ± 23.3 vs. 27.7 ± 23.6). At visit 4, lower PSS-10 score (13.0 ± 5.0 vs. 18.7 ± 4.6; <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>p</a:mi> <a:mo>&lt;</a:mo> <a:mn>.0001</a:mn> </a:math> ), serum cortisol levels <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mfenced open="(" close=")" separators="|"> <c:mrow> <c:mi>p</c:mi> <c:mo>=</c:mo> <c:mn>0.0443</c:mn> </c:mrow> </c:mfenced> </c:math> , and Pittsburgh Sleep Quality Index (PSQI) score <h:math xmlns:h="http://www.w3.org/1998/Math/MathML" id="M3"> <h:mfenced open="(" close=")" separators="|"> <h:mrow> <h:mi>p</h:mi> <h:mo>&lt;</h:mo> <h:mn>.0001</h:mn> </h:mrow> </h:mfenced> </h:math> but higher Oxford Happiness Questionnaire (OHQ) scores <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" id="M4"> <m:mfenced open="(" close=")" separators="|"> <m:mrow> <m:mi>p</m:mi> <m:mo>&lt;</m:mo> <m:mn>.0001</m:mn> </m:mrow> </m:mfenced> </m:math> were seen in Ashwagandha SR vs. the placebo group, suggesting significantly lower stress levels and significantly better psychological well-being and sleep quality in the former. No adverse events were reported. Conclusions. This is the first clinical study assessing Ashwagandha SR for its safety and efficacy. Treatment with one Ashwagandha SR capsule once daily for 90 days improved memory and focus, psychological well-being, and sleep quality, reduced stress levels, and was safe and well-tolerated.

Unlocking the Therapeutic Potential of Medicinal Plants for Alzheimer’s Disease: Preclinical to Clinical Trial Insights

Kushagra Nagori, Kartik T. Nakhate, Krishna Yadav +2 more · Future Pharmacology · 2023 · 48 citations

Alzheimer’s disease (AD) is a progressive, multifactorial, and unremitting neurodegenerative disease characterized by memory loss, personality changes, and cognitive impairment. It has become more prevalent in recent years. Therefore, understanding the pathophysiology of AD and developing efficient therapeutic strategies are essential. Moreover, the progression of the disease is unaffected by the pharmaceutical approaches discovered to date. Additionally, the failure of over 200 potential drug candidates in clinical trials over the past decade suggests the complexity and difficulty of both the disease and its underlying causes. Therefore, research focused on medicinal plant-based natural products in the search for novel neuroprotective therapeutic candidates for AD is essential. Indeed, several scientific investigations have demonstrated the efficacy of many medicinal plants and their principal phytochemicals in the treatment of AD. This review article covered the pathophysiological mechanisms of AD, the necessity for natural products as anti-AD treatments, and the most recent preclinical studies revealing the function of neuroprotective medicinal plants and their bioactive compounds in the effective management of AD. In addition, the review also presents clinical trial data of promising anti-AD formulations/agents of plant origin. Revealing recent findings and highlighting the clinical trial data related to the development of new treatments for AD would promote further research in this field and pave the way for the development of more effective and safe treatments for this debilitating disease.

Intermittent fasting interventions to leverage metabolic and circadian mechanisms for cancer treatment and supportive care outcomes

Faiza Kalam, Dara James, Yun Rose Li +6 more · JNCI Monographs · 2023 · 37 citations

Intermittent fasting entails restricting food intake during specific times of day, days of the week, religious practice, or surrounding clinically important events. Herein, the metabolic and circadian rhythm mechanisms underlying the proposed benefits of intermittent fasting for the cancer population are described. We summarize epidemiological, preclinical, and clinical studies in cancer published between January 2020 and August 2022 and propose avenues for future research. An outstanding concern regarding the use of intermittent fasting among cancer patients is that fasting often results in caloric restriction, which can put patients already prone to malnutrition, cachexia, or sarcopenia at risk. Although clinical trials do not yet provide sufficient data to support the general use of intermittent fasting in clinical practice, this summary may be useful for patients, caregivers, and clinicians who are exploring intermittent fasting as part of their cancer journey for clinical outcomes and symptom management.

A randomized, placebo-controlled trial investigating the acute and chronic benefits of American Ginseng (Cereboost®) on mood and cognition in healthy young adults, including in vitro investigation of gut microbiota changes as a possible mechanism of action

Lynne Bell, Adrian R. Whyte, Cindy Duysburgh +6 more · European Journal of Nutrition · 2021 · 44 citations

PURPOSE: Cereboost®, an American ginseng extract, has shown improved short-term memory and attention/alertness in healthy young and middle-aged individuals, potentially via modulation of the gut microbiome and upregulation of neurotransmitters such as acetylcholine. Here, we explored the effects of Cereboost® on cognition and mood in the first 6 h post intervention (acute), after 2 weeks daily supplementation (chronic), and whether 2 weeks daily supplementation altered the response to a single acute dose (acute-on-chronic). A concurrent in vitro study evaluated effects of repeated Cereboost® administration on human gut microbiota. METHODS: Cognitive effects of Cereboost® were assessed using a double-blind, randomized, placebo-controlled clinical trial, with 61 healthy young adults. Modulation of the gut microbiome was concurrently modelled using the Simulator of the Human Microbial Ecosystem (SHIME®), using a young adult donor. RESULTS: Consistent with previous findings, Cereboost® improved working memory and attention during the immediate postprandial period; effects that were amplified following two weeks' treatment (acute-on-chronic) compared to acute testing alone. Chronic supplementation improved cognition on an acetylcholine-sensitive attention task and improved mental fatigue and self-assurance aspects of mood. The parallel in vitro study revealed significantly increased acetate, propionate, and butyrate levels in simulated proximal and distal colon regions, linked with observed increases in Akkermansia muciniphila and Lactobacillus. CONCLUSION: This study confirmed the promising effects of Cereboost® on cognitive function and mood, while suggesting a possible link to alterations of the gut microbiome and modulation of acetylcholine. Further studies will be required to unravel the underlying mechanisms that are involved. REGISTRATION: The study was pre-registered at ClinicalTrials.gov on 6th July 2018 (Identifier: NCT03579095).

The use of integrative therapy based on Yoga and Ayurveda in the treatment of a high-risk case of COVID-19/SARS-CoV-2 with multiple comorbidities: a case report

Alka Mishra, Sumitra A. Bentur, Sonika Thakral +2 more · Journal of Medical Case Reports · 2021 · 44 citations

BACKGROUND: We report a high-risk case of a coronavirus disease 19 (COVID-19)-positive patient with comorbidities including diabetes mellitus (DM), hypertension (HTN), hypothyroidism and chronic kidney disease (CKD), treated successfully using an integrative therapy plan based on Ayurveda and Yoga, along with government-mandated compulsory modern western medicine (MWM) treatment. Recently, some evidence has been emerging on the use of Ayurveda for treatment of COVID-19. The classical texts of Ayurvedic medicine such as Charaka Samhita and Sushruta Samhita contain descriptions of pandemics of similar proportions and describe them as Janapadoddhvansa, meaning the destruction of communities, along with their causes and treatment. CASE PRESENTATION: The case reported herein is a 55-year-old man from Delhi, India, with confirmed (tested) COVID-19, who first took MWM for 7 days before seeking integrative therapy. The patient has comorbidities including DM, HTN, hypothyroidism and CKD and had developed symptoms including fever (which was resolved by the time integrative therapy was started), sore throat, dry cough, body aches, weakness, bad taste and smell, and heaviness in the abdomen. Based on the patient's symptoms and comorbidities, a treatment plan including Ayurvedic medicines, Yoga protocol, dietary recommendations and lifestyle modifications was prescribed by a registered Ayurveda doctor and a Yoga consultant. The patient started experiencing improvement in all the symptoms within 2 days after starting the treatment; he reported approximately [Formula: see text] relief from the symptoms after 5 days, and almost complete relief within 9 days. Also, the blood sugar levels (both fasting blood sugar [FBS] and postprandial blood sugar [PPBS]) exhibited significant improvement after 5 days, and decreased to within the normal range within 12 days. Besides relief in symptoms, the patient's real-time reverse transcription polymerase chain reaction (RT-PCR) test done on the 19th day returned negative results. CONCLUSIONS: Integrative therapy was found to be effective in mitigating the symptoms of COVID-19 in this patient with multiple comorbidities. Moreover, a significant improvement in blood sugar levels (not under control with modern medicine) was also achieved. Integrative therapy based on the classical texts of Ayurveda and Yoga may offer a promising and scalable treatment option for COVID-19 patients. A case series or a suitably designed randomized controlled trial is needed to assess its efficacy.

Rhodiola rosea L. Improves Learning and Memory Function: Preclinical Evidence and Possible Mechanisms

Gouping Ma, Qun Zheng, Meng-Bei Xu +4 more · Frontiers in Pharmacology · 2018 · 28 citations

Rhodiola rosea L. (R. rosea L.) is widely used to stimulate the nervous system, extenuate anxiety, enhance work performance, relieve fatigue, and prevent high altitude sickness. Previous studies reported that R. rosea L. improves learning and memory function in animal models. Here, we conducted a systematic review and meta-analysis for preclinical studies to assess the current evidence for R. rosea L. effect on learning and memory function. Ultimately, 36 studies involving 836 animals were identified by searching 6 databases from inception to May 2018. The primary outcome measures included the escape latency in Morris water maze (MWM) test on behalf of learning ability, the frequency and the length of time spent on the target quadrant in MWM test representing memory function, and the number of errors in step down test, dark avoidance test and Y maze test on behalf of memory function. The secondary outcome measures were mechanisms of R. rosea L. for learning and/or memory function. Compared with control, the pooled results of 28 studies showed significant effects of R. rosea L. for reducing the escape latency (P<0.05); 23 studies for increasing the frequency and the length of time spent on the target quadrant (P<0.05); and 6 studies for decreasing the number of errors (P<0.01). The possible mechanisms of R. rosea L. are largely through antioxidant, cholinergic regulation, anti-apoptosis activities, anti-inflammatory, improving coronary blood flow and cerebral metabolism. In conclusion, the findings suggested that R. rosea L. can improve learning and memory function.

Phytoconstituents of Withania somnifera unveiled Ashwagandhanolide as a potential drug targeting breast cancer: Investigations through computational, molecular docking and conceptual DFT studies

Hittanahallikoppal Gajendramurthy Gowtham, M. Murali, Sudarshana Brijesh Singh +14 more · PLoS ONE · 2022 · 39 citations

Breast cancer is the second most common malignancy in females worldwide and poses a great challenge that necessitates the identification of novel therapeutic agents from several sources. This research aimed to study the molecular docking and molecular dynamics simulations of four proteins (such as PDB: 6CBZ, 1FDW, 5GWK and 2WTT) with the selected phytochemicals from Withania somnifera to identify the potential inhibitors for breast cancer. The molecular docking result showed that among 44 compounds, two of them, Ashwagandhanolide and Withanolide sulfoxide have the potential to inhibit estrogen receptor alpha (ERα), 17-beta-hydroxysteroid -dehydrogenase type 1 (17β-HSD1), topoisomerase II alpha (TOP2A) and p73 tetramerization domain that are expressed during breast cancer. The molecular dynamics (MD) simulations results suggested that Ashwagandhanolide remained inside the binding cavity of four targeted proteins and contributed favorably towards forming a stable protein-ligand complex throughout the simulation. Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties confirmed that Ashwagandhanolide is hydrophobic and has moderate intestinal permeability, good intestinal absorption, and poor skin permeability. The compound has a relatively low VDss value (-1.652) and can be transported across ABC transporter and good central nervous system (CNS) permeability but did not easily cross the blood-brain barrier (BBB). This compound does not possess any mutagenicity, hepatotoxicity and skin sensitization. Based on the results obtained, the present study highlights the anticancer potential of Ashwagandhanolide, a compound from W. somnifera. Furthermore, in vitro and in vivo studies are necessary to perform before clinical trials to prove the potentiality of Ashwagandhanolide.

Emerging Vistas for the Nutraceutical Withania somnifera in Inflammaging

Vivek Basudkar, Gunjan Gujrati, Saiprasad Ajgaonkar +3 more · Pharmaceuticals · 2024 · 23 citations

Inflammaging, a coexistence of inflammation and aging, is a persistent, systemic, low-grade inflammation seen in the geriatric population. Various natural compounds have been greatly explored for their potential role in preventing and treating inflammaging. Withania somnifera has been used for thousands of years in traditional medicine as a nutraceutical for its numerous health benefits including regenerative and adaptogenic effects. Recent preclinical and clinical studies on the role of Withania somnifera and its active compounds in treating aging, inflammation, and oxidative stress have shown promise for its use in healthy aging. We discuss the chemistry of Withania somnifera, the etiology of inflammaging and the protective role(s) of Withania somnifera in inflammaging in key organ systems including brain, lung, kidney, and liver as well as the mechanistic underpinning of these effects. Furthermore, we elucidate the beneficial effects of Withania somnifera in oxidative stress/DNA damage, immunomodulation, COVID-19, and the microbiome. We also delineate a putative protein–protein interaction network of key biomarkers modulated by Withania somnifera in inflammaging. In addition, we review the safety/potential toxicity of Withania somnifera as well as global clinical trials on Withania somnifera. Taken together, this is a synthetic review on the beneficial effects of Withania somnifera in inflammaging and highlights the potential of Withania somnifera in improving the health-related quality of life (HRQoL) in the aging population worldwide.

In Quest of the Mysterious Holistic Vedic Herb Bacopa monnieri (L.) Pennell

Sumanta Mondal, Kausik Bhar, Prasenjit Mondal +6 more · Pharmacognosy Research · 2023 · 24 citations

Pharmacognosy Research,2023,15,3,410-454.DOI:10.5530/pres.15.3.045Published:June 2023Type:Review ArticleAuthors:Sumanta Mondal, Kausik Bhar, Prasenjit Mondal, Naresh Panigrahi, Suvendu Kumar Sahoo, Pydi Swetha, Subhadip Chakraborty, Nooka Yaswanth Teja, and Neha Parveen Author(s) affiliations:Sumanta Mondal1,*, Kausik Bhar1, Prasenjit Mondal2, Naresh Panigrahi1, Suvendu Kumar Sahoo1, Pydi Swetha1, Subhadip Chakraborty1, Nooka Yaswanth Teja1, Neha Parveen1 1Department of Pharmaceutical Chemistry, School of Pharmacy, GITAM (Deemed to be University), Visakhapatnam, Andhra Pradesh, INDIA. 2Department of Pharmaceutical Technology, Brainware University, Kolkata, West Bengal, INDIA. Abstract:Throughout history, complementary and alternative therapies have been widely utilised. In recent years, there has been a surge in interest in the usage of herbal treatments all around the world. Various natural chemicals, such as those produced from plants, have been investigated as potential therapies for a myriad of ailments. The essence of this review was to methodically describe everything we know about Bacopa monnieri (L.) Pennell, a mysterious holistic Vedic herb belonging to the Plantaginaceae family, a well-known nootropic and effective memory enhancer, which has recently emerged as one of the most important medical herbs, widely used therapeutically in the Orient and growing in popularity around the world. Literature was gathered from sources such as Scopus, PubMed, Google Scholar, and ScienceDirect, and reviewed using the Prisma quality metacritic paradigm. It is now plainly obvious that current therapies fall short of meeting the demands of the vast majority of individuals with health problems, and traditional medicines are gaining appeal as a result of their reduced toxicity. Bacopa is a traditional herb used in Ayurvedic medicine to treat brain and nerve weariness, as well as in Siddha medicine to treat impaired memory. It's also used to cure brain and nerve exhaustion in Unani medicine. We improved Brahmi micropropagation and secondary metabolite biosynthesis by compiling pharmacobotanical and pharmacognostical descriptions, as well as ethnoarchaeological data and nanotechnology domination. This critique also highlights our contemporary information of pharmacological activity, preclinical and clinical investigations, significant bioactives, reported mechanisms of action, clinical effectiveness, safety, and the potential for herb-drug interactions. At the same time, the current incarnation of research at the plant is reviewed, as well as future research possibilities. Brahmi offers a lot of potential for treating a range of illnesses, including neuro-pharmacological, depression, inflammation, hepatoprotective, antidiabetic, and others. According to the presumptions of this review, further clinical trials and research are needed. While the impact of Brahmi as an anxiolytic and antidepressant has to be explored further, its potential as an anti-epileptic therapy and a treatment for antiepileptic drugs side effects is also being researched. Furthermore, Brahmi's antioxidant ability may explain, at least in part, the antistress, immunomodulatory, cognition-facilitating, anti-inflammatory, and anti-aging benefits documented in experimental animals and clinical circumstances, necessitating further study into its other therapeutic characteristics. Keywords:Bacopa monnieri, Cheminformatics, Clinical trials, Herpestis monnieri, Pharmacological Testimony, Phytomolecules., PlantaginaceaeView:PDF (1.93 MB)

Effect of standardized root extract of ashwagandha (<i>Withania somnifera</i>) on well‐being and sexual performance in adult males: A randomized controlled trial

Sanjaya Chauhan, Manoj Srivastava, Anklesh Kumar Pathak · Health Science Reports · 2022 · 44 citations

Abstract Background and Aim In Ayurveda, ashwagandha is a popular plant for promoting youthful energy, longevity, and overall well‐being. It is also an excellent aphrodisiac herb that aids in the improvement and maintenance of normal sexual health. The present study aims to evaluate the effect of ashwagandha root extract on improving sexual health in adult males. Methods In this 8‐week randomized, double‐blind, placebo‐controlled study, we investigated the aphrodisiac property of an ashwagandha root extract in adult males. Fifty participants with lower sexual desire were randomly allocated to take 300 mg of ashwagandha root extract or placebo capsules twice daily. Outcomes were measured using the derogatis interview for sexual functioning‐male (DISF‐M) questionnaire, serum testosterone, serum prolactin, and short‐form survey—36 quality of life questionnaire before and after the intervention. Results Compared to placebo, ashwagandha root extract supplementation was associated with a statistically significant increase in the total DISF‐M scores (mean difference −9.8; 95% confidence interval, −10.73 to −8.87; p &lt; 0.0001; t ‐test). It was also associated with a statistically significant increase in serum testosterone levels (−66.52; −80.70 to −52.34; p &lt; 0.0001; t ‐test). However, the prolactin level did not change after intervention in both the ashwagandha and placebo groups (−1.06; −2.78 to 0.66; p &gt; 0.05). Conclusion These findings suggest that ashwagandha demonstrated a significant subjective perception of sexual well‐being and assisted in increasing serum testosterone levels in the participants.

Efficacy and Safety of Ashwagandha (<i>Withania somnifera</i>) Root Extract in Improving Sexual Function in Women: A Pilot Study

Swati Dongre, Deepak Langade, Sauvik Bhattacharyya · BioMed Research International · 2015 · 82 citations

BACKGROUND: Many women experience sexual dysfunction where there are orgasm disorders and sexual difficulties. Ashwagandha (Withania somnifera) is a herb known to improve the body's physical and psychological condition. OBJECTIVE: The purpose of the study was to determine the efficacy and safety of a high-concentration ashwagandha root extract (HCARE) supplementation for improving sexual function in healthy females. METHODS: In this pilot study, 50 study subjects were randomized to either (i) HCARE-treated group or (ii) placebo- (starch-) treated group. The subjects consumed either HCARE or placebo capsules of 300mg twice daily for 8 weeks. Sexual function was assessed using two psychometric scales, the Female Sexual Function Index (FSFI) Questionnaire and the Female Sexual Distress Scale (FSDS), and by the number of total and successful sexual encounters. RESULTS: The analysis indicates that treatment with HCARE leads to significantly higher improvement, relative to placebo, in the FSFI Total score (p < 0.001), FSFI domain score for "arousal" (p < 0.001), "lubrication" (p < 0.001), "orgasm" (p = 0.004), and "satisfaction" (p < 0.001), and also FSDS score (p < 0.001) and the number of successful sexual encounters (p < 0.001) at the end of the treatment. CONCLUSIONS: This study demonstrated that oral administration of HCARE may improve sexual function in healthy women. The present study is registered in the Clinical Trial Registry, Government of India, with a number CTRI/2015/07/006045.

Efficacy and safety of bupropion in cancer-related fatigue, a randomized double blind placebo controlled clinical trial

Ebrahim Salehifar, Saeed Azimi, Ghasem Janbabai +4 more · BMC Cancer · 2020 · 27 citations

BACKGROUND AND OBJECTIVES: Cancer-related fatigue (CRF) is one of the most prevalent complications experienced by cancer patients during and after the process of treatment. Despite conducting a lot of studies, there is no approved therapy to help manage CRF. This study aims to investigate the efficacy of bupropion on CRF. MATERIALS AND METHODS: In this double-blind randomized placebo-controlled clinical trial, a total of 30 eligible cancer patients suffering from fatigue were randomly divided into two groups (15 patients in each group). Bupropion was administered 75 mg/day for the first three days and 150 mg/day (divided in two doses) till the end of the study at week 6. Fatigue as the primary outcome was measured by BFI (Brief Fatigue Inventory) and FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy) scales. Secondary outcomes included HADS (Hospital Anxiety and Depression Scale) and performance status (PS) measured by Karnofsky and ECOG (Eastern Cooperative Oncology Group) scales. Assessments were done at baseline, end of the second and sixth week. RESULTS: There was no significant difference between placebo and bupropion at baseline and the end of second week. Significant difference was seen between two groups at the end of week six (P = 0.006 based on BFI) in favor of bupropion. In-group assessment showed improvement in fatigue levels in both groups during study time (P = 0.000 based on BFI for both bupropion and placebo). Secondary outcomes (e.g., HADS and PS) were not different at baseline and the end of second week. However, at the end of week six, the difference was significant in favor of bupropion. CONCLUSION: A six-week trial of bupropion reduces the CRF and improves the PS of cancer patients. TRIAL REGISTRATION: Current Controlled Trials IRCT20090613002027N12, registration date: 2018-06-01.

Two-month period of 500 mg lecithin-based delivery form of quercetin daily dietary supplementation counterbalances chronic fatigue symptoms: A double-blind placebo controlled clinical trial

Mariangela Rondanelli, Antonella Riva, Giovanna Petrangolini +2 more · Biomedicine & Pharmacotherapy · 2023 · 12 citations

BACKGROUND: Chronic fatigue (CF) is a complex phenomenon without clear etiology that may require long-term treatment, but to date, no specific therapy has been identified for it. Some botanicals might be helpful in the management of CF. Among these botanicals, quercetin demonstrates its capacity to modulate multiple biological pathways and acknowledged major properties in CF: antioxidant, anti-inflammatory, immunomodulating, improving exercise endurance, enhancing mitochondrial biogenesis, repairing mitochondrial dysfunction. PURPOSE: Given this background, the aim of this study was to evaluate if a 2-month period of daily Quercetin Phytosome™ 500 mg supplementation is of benefit for the relief of CF. METHODS: The primary end point has been the evaluation of fatigue, by Fatigue Impact Scale (FIS-40). The secondary end points have been the assessment of sleep, by Pittsburgh Sleep Quality Index (PSQI), evaluation of muscle performance, by short physical performance battery and by wearable armband-shaped sensor in order to evaluate the number of steps, body composition, by DXA and quality of life by Short-Form 12-Item Health Survey (SF-12). RESULTS: Seventy-eight subjects (42 F; 36 M) (mean age 56 ± 9) reporting CF symptoms, completed the study (placebo/supplement 38/40). The FIS-40 mean difference changes between groups (supplement minus placebo) was - 10.583 points (CI95% -11.985; -9.182) (p < 0.001). Also, statistically significant changes between groups have been recorded in Pittsburgh Sleep Quality Index - 2.040 points (CI95%: -2.770; -1.309), p < 0.01), number of steps 1443.152 (CI95%: 1199.556; 1686.749), and SPPB (score) 0.248 (CI95%: 0.105; 0.391) (p < 0.001). CONCLUSION: The quercetin supplementation counterbalances CF symptoms.

Adaptogenic Ashwagandha root extract modulates inflammatory markers in feline stress management: a double-blind placebo-controlled clinical trial

Ashok Kumar Devarasetti, Kala Kumar Bharani, Amit Khurana +7 more · Journal of Applied Animal Research · 2024 · 10 citations

This study aimed to evaluate the safety and efficacy of oral administration of Ashwagandha root extract (ARE) in cats subjected to different types of stress.A randomized, double-blind, placebo-controlled veterinary clinical trial was conducted with sixteen healthy pet cats.Each cat was randomly assigned to receive ARE (15 mg/kg body weight) or a placebo and were subjected to four types of stress over a period of one month.No detrimental changes were observed in ALP, ALT, AST, glucose, creatinine, and BUN levels on day 30 with ARE with all values within the physiological range.Additionally, in the AREtreated group, the protein (p < 0.05) and albumin (p < 0.01) levels were increased significantly, indicating overall improved liver function.Post 30 days ARE treatment, significant modulation of malondialdehyde (MDA) (p < 0.001), superoxide dismutase (SOD) (p < 0.001), glutathione (GSH) (p < 0.01) and catalase (p < 0.001) levels were observed with ARE compared to placebo control group.After 30 days ARE treatment, serum cortisol levels significantly decreased (p < 0.001), indicating strong anti-stress effects.There was a significant decrease in cytokine levels (TNF-, IFN- & IL-10), NFB and Nrf-2 levels in ARE treated group indicating potent anti-inflammatory effects.Overall, these promising results demonstrate that ARE possesses adaptogenic and anti-inflammatory properties and is safe in felines.

Naturopathic Care for Anxiety: A Randomized Controlled Trial ISRCTN78958974

Kieran Cooley, Orest Szczurko, Dan Perri +4 more · PLoS ONE · 2009 · 112 citations

BACKGROUND: Anxiety is a serious personal health condition and represents a substantial burden to overall quality of life. Additionally anxiety disorders represent a significant cost to the health care system as well as employers through benefits coverage and days missed due to incapacity. This study sought to explore the effectiveness of naturopathic care on anxiety symptoms using a randomized trial. METHODS: Employees with moderate to severe anxiety of longer than 6 weeks duration were randomized based on age and gender to receive naturopathic care (NC) (n = 41) or standardized psychotherapy intervention (PT) (n = 40) over a period of 12 weeks. Blinding of investigators and participants during randomization and allocation was maintained. Participants in the NC group received dietary counseling, deep breathing relaxation techniques, a standard multi-vitamin, and the herbal medicine, ashwagandha (Withania somnifera) (300 mg b.i.d. standardized to 1.5% with anolides, prepared from root). The PT intervention received psychotherapy, and matched deep breathing relaxation techniques, and placebo. The primary outcome measure was the Beck Anxiety Inventory (BAI) and secondary outcome measures included the Short Form 36 (SF-36), Fatigue Symptom Inventory (FSI), and Measure Yourself Medical Outcomes Profile (MY-MOP) to measure anxiety, mental health, and quality of life respectively. Participants were blinded to the placebo-controlled intervention. RESULTS: Seventy-five participants (93%) were followed for 8 or more weeks on the trial. Final BAI scores decreased by 56.5% (p<0.0001) in the NC group and 30.5% (p<0.0001) in the PT group. BAI group scores were significantly decreased in the NC group compared to PT group (p = 0.003). Significant differences between groups were also observed in mental health, concentration, fatigue, social functioning, vitality, and overall quality of life with the NC group exhibiting greater clinical benefit. No serious adverse reactions were observed in either group. RELEVANCE: Many patients seek alternatives and/or complementary care to conventional anxiety treatments. To date, no study has evaluated the potential of a naturopathic treatment protocol to effectively treat anxiety. Knowledge of the efficacy, safety or risk of natural health products, and naturopathic treatments is important for physicians and the public in order to make informed decisions. INTERPRETATION: Both NC and PT led to significant improvements in patients' anxiety. Group comparison demonstrated a significant decrease in anxiety levels in the NC group over the PT group. Significant improvements in secondary quality of life measures were also observed in the NC group as compared to PT. The whole system of naturopathic care for anxiety needs to be investigated further including a closer examination of the individual components within the context of their additive effect. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN78958974.

Ashwagandha as an Adaptogen: Its Influence on Sleep Patterns, Stress Response, and Anxiety in Modern Life

Mateusz Haber, Adrianna Czachor, Paula Kula +6 more · Journal of Education Health and Sport · 2024 · 7 citations

Background: Ashwagandha (Withania somnifera), a prominent adaptogen in traditional Ayurvedic medicine, has gained substantial attention for its potential to enhance resilience to modern stressors, improve sleep quality, and alleviate anxiety. Preclinical and clinical studies have demonstrated that Ashwagandha’s active compounds, particularly withanolides, influence the hypothalamic-pituitary-adrenal (HPA) axis, leading to reductions in cortisol levels and a more balanced stress response. Puropose: This review aims to consolidate current evidence on Ashwagandha’s efficacy in modulating stress response, improving sleep patterns, and reducing anxiety levels. Material and methods: The review was based on the analysis of materials collected in the databases "Pubmed", Google Scholar, ResearchGate, books and other scientific articles. The search was conducted using keywords: “Ashwagandha”, “Withania somnifera”, “adaptogen”, “stress”, “anxiety”, “sleep”, “cortisol”. “HPA axis”. Results: A review of the literature has shown Ashwagandha anxiolytic properties, with effects comparable to standard anti-anxiety medications but with fewer side effects. Additionally, Ashwagandha has been shown to significantly improve sleep onset latency, sleep duration, and overall sleep quality, particularly in individuals suffering from stress-induced sleep disorders. Conclusions: Ashwagandha shows significant potential as a natural therapy for managing stress, improving sleep quality, and reducing anxiety, primarily through its effects on the hypothalamic-pituitary-adrenal (HPA) axis and cortisol regulation. Clinical trials have demonstrated its efficacy in improving sleep patterns and reducing anxiety, with a generally favorable safety profile. However, there is a need for further research, particularly to better understand the long-term effects and safety of Ashwagandha supplementation.

Exploring the Role of Phytochemicals in Managing Depression: Mechanisms, Therapeutic Potential, and Future Directions.

Sodiq Balogun, Michael Ajen, Sunday Igboke +3 more · AROC in Pharmaceutical and Biotechnology · 2025 · 6 citations

Background: Depression is a globally prevalent psychiatric disorder, and while conventional pharmacotherapies have transformed care, they are often limited by delayed onset, suboptimal efficacy, and side effects. Emerging evidence links chronic inflammation, oxidative stress, HPA axis dysregulation, neurotrophic deficits, and gut-brain axis disturbances to Major Depressive Disorder (MDD) pathophysiology. In this context, phytochemicals bioactive plant compounds show promise as adjuncts or alternatives. This review explores major phytochemical classes (flavonoids, alkaloids, terpenoids, saponins, lignans, glycosides), highlighting their antidepressant mechanisms, including monoaminergic modulation, anti-inflammation, antioxidant effects, neuroplasticity enhancement (via BDNF), HPA axis regulation, and gut microbiota influence. Notable agents like curcumin, resveratrol, berberine, ashwagandha, and Rhodiola rosea have demonstrated efficacy in preclinical and clinical settings. Traditional medical systems also utilize synergistic multi-herb formulations. Despite their potential, challenges such as poor bioavailability, lack of standardization, potential herb-drug interactions, and regulatory inconsistencies impede clinical translation. Future directions involve personalized phytomedicine, bioavailability-enhancing technologies, systems biology, and large-scale randomized controlled trials to establish efficacy and safety. Overall, phytochemicals offer a scientifically grounded and patient-friendly avenue for advancing depression therapeutics.

The Effect of Herbal Medicine on Suicidal Behavior: A Protocol for Systematic Review and Meta-Analysis

Chan‐Young Kwon, Boram Lee · Healthcare · 2023 · 4 citations

Suicide is an important social and medical problem worldwide, including in countries that use traditional East Asian medicine (TEAM). Herbal medicine (HM) has been reported to be effective against several suicide-related conditions. This systematic review aimed to investigate the efficacy and safety of HM in reducing suicidal behavior including suicidal ideation, attempts, or completed suicide. We conduct a comprehensive search in 15 electronic bibliographic databases from inception to September 2022. All types of prospective clinical studies-including randomized controlled clinical trials (RCTs)-involving HM without or with routine care are included. The primary outcomes of this review are validated measures of suicidal ideation including the Beck scale for suicidal ideation. The revised Cochrane's risk of bias tool and other tools including the ROBANS-II tool are used to assess the methodological quality of RCTs and non-RCTs, respectively. A meta-analysis is performed using RevMan 5.4 in cases of homogeneous data from controlled studies. The results of the systematic review provide high-quality evidence to determine the efficacy and safety of HM for suicidal behavior. Our findings are informative for clinicians, policymakers, and researchers, aimed at reducing suicide rates, especially in countries that use TEAM.

An Overview of Herbal Nutraceuticals, Their Extraction, Formulation, Therapeutic Effects and Potential Toxicity

Vaishnavi Bommakanti, Amruthamol Puthenparambil Ajikumar, Chelssa Sivi +6 more · Separations · 2023 · 83 citations

Herbal nutraceuticals are foods derived from plants and/or their derivatives, such as oils, roots, seeds, berries, or flowers, that support wellness and combat acute and chronic ailments induced by unhealthful dietary habits. The current review enlists various traditional as well as unexplored herbs including angelica, burnet, caraway, laurel, parsley, yarrow, and zedoary, which are rich sources of bioactive components, such as aloesin, angelicin, trans-anethole, and cholesteric-7-en-3β-ol. The review further compares some of the extraction and purification techniques, namely, Soxhlet extraction, ultrasound assisted extraction, microwave assisted extraction, supercritical fluid extraction, accelerated solvent extraction, hydro-distillation extraction, ultra-high-pressure extraction, enzyme assisted extraction, pulsed electric field extraction, bio affinity chromatography, cell membrane chromatography, and ligand fishing. Herbal nutraceuticals can be purchased in varied formulations, such as capsules, pills, powders, liquids, and gels. Some of the formulations currently available on the market are discussed here. Further, the significance of herbal nutraceuticals in prevention and cure of diseases, such as diabetes, obesity, dementia, hypertension, and hypercholesterolemia; and as immunomodulators and antimicrobial agents has been discussed. Noteworthy, the inappropriate use of these herbal nutraceuticals can lead to hepatotoxicity, pulmonary toxicity, cytotoxicity, carcinogenicity, nephrotoxicity, hematotoxicity, and cardiac toxicity. Hence, this review concludes with a discussion of various regulatory aspects undertaken by the government agencies in order to minimize the adverse effects associated with herbal nutraceuticals.

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

V. G. Vaidya, Amol Gothwad, Gayatri Ganu +3 more · Journal of Ayurveda and Integrative Medicine · 2023 · 29 citations

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.

Online Yoga and Ayurveda Intervention as Tertiary Prevention of Psychological Comorbidities in COVID-19 Survivors: A Randomized Controlled Trial

Rudra B. Bhandari · Annals of Neurosciences · 2022 · 15 citations

Background and Purpose About 56% of symptomatic COVID-19 survivors have been found with neuropsychological comorbidities, such as depression, anxiety, posttraumatic stress disorders (PTSD), and impaired quality of life (QoL). Alongside, antimicrobial, anti-inflammatory, neuroprotective, regenerative, immunomodulatory, cardio-pulmonary health promotive, and psychological benefits of yogic and Ayurvedic intervention are well documented. Therefore, this study aimed to assess the effect of online Yoga (OYI) and Yoga cum Ayurveda intervention (OYAI) on COVID-19-induced depression, anxiety, PTSD, and poor QoL. Method Seventy-two participants (males/females: 33/26) with at least a 3-month back history of symptomatic COVID-19 infection and age (mean ± SD: 32.33 ± 9.9 and 33.04 ± 12.9 for males and females, respectively) were recruited from Patanjali Ayurveda Hospital, Haridwar, India, and All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India, before random allocation into an equal-sized control group (CG), Yoga group (YG) and Yoga cum concoction (YCG) group. Split-plot analysis of variance and Kruskal–Wallis tests with Bonferroni adjusted post hoc comparisons were computed for normal and nonnormal data using IBM SPSS (25th Version, SPSS South Asia Private Limited, Bangalore, India). Results Both the treatments—the 30-day OYI and OYAI, significantly improved depression ( P &lt; .002, ES: -0.99 and P &lt; .001, ES: -2.11), anxiety ( P &lt; .001, ES: -1.32 and -1.89), PTSD ( P &lt; .001, ES: -1.8 and -1.83) and QoL related constructs ( P &lt; .001, ES: 0.63 and 0.76; 0.71 and 0.93 for each OYI and OYAI versus general health and physical health; P &lt; .001, ES: 0.65 for OYAI versus psychological health; and P &lt; .003, ES: 0.54 for OYI versus environment) of the participants compared to the controls. Conclusion OYAI may better ameliorate COVID-19-induced psychological comorbidities than OYI with no adverse effects.

Multicenter, open-label, exploratory clinical trial with &lt;em&gt;Rhodiola rosea&lt;/em&gt; extract in patients suffering from burnout symptoms

Siegfried Kasper, Angelika Dienel · Neuropsychiatric Disease and Treatment · 2017 · 28 citations

Purpose: This study is the first clinical trial aiming to explore the clinical outcomes in burnout patients treated with Rhodiola rosea . The reported capacity of R. rosea to strengthen the organism against stress and its good tolerability offer a promising approach in the treatment of stress-related burnout. The aim of the treatment was to increase stress resistance, thus addressing the source rather than the symptoms of the syndrome and preventing subsequent diseases associated with a history of burnout. The objective of the trial was to provide the exploratory data required for planning future randomized trials in burnout patients in order to investigate the clinical outcomes of treatment with R. rosea dry extract in this target group. Methods: The study was planned as an exploratory, open-label, multicenter, single-arm trial. A wide range of rating scales were assessed and evaluated in an exploratory data analysis to generate hypotheses regarding clinical courses and to provide a basis for the planning of subsequent studies. A total of 118 outpatients were enrolled. A daily dose of 400 mg R. rosea extract (WS ® 1375, Rosalin) was administered over 12 weeks. Clinical outcomes were assessed by the German version of the Maslach Burnout Inventory, Burnout Screening Scales I and II, Sheehan Disability Scale, Perceived Stress Questionnaire, Number Connection Test, Multidimensional Mood State Questionnaire, Numerical Analogue Scales for different stress symptoms and impairment of sexual life, Patient Sexual Function Questionnaire, and the Clinical Global Impression Scales. Results: The majority of the outcome measures showed clear improvement over time. Several parameters had already improved after 1 week of treatment and continued to improve further up to the end of the study. The incidence of adverse events was low with 0.015 events per observation day. Discussion: The trial reported here was the first to investigate clinical outcomes in patients suffering from burnout symptoms when treated with R. rosea . During administration of the study drug over the course of 12 weeks, a wide range of outcome measures associated with the syndrome clearly improved. Conclusion: The results presented provide an encouraging basis for clinical trials further investigating the clinical outcomes of R. rosea extract in patients with the burnout syndrome. Keywords: burnout, clinical study, Rhodiola rosea

Therapeutic Role of Medicinal Plants in Combating Air Pollution-Induced Inflammation and Anxiety

Tanvi Rathore, Era Upadhyay, Arvind K Jain · International Journal of Environmental Sciences · 2025 · 1 citations

Air pollution, particularly fine particulate matter (PM₂.₅), is a major global health concern, contributing to various acute and chronic diseases. PM₂.₅ induces oxidative stress and inflammation, leading to cardiovascular, respiratory, and neuropsychiatric disorders, including anxiety and depression. In India, energy practices significantly contribute to both indoor and outdoor air pollution, highlighting the need for sustainable solutions. Increasing interest in natural therapeutics, particularly medicinal plants, has emerged due to their anti-inflammatory and anxiolytic properties. This review explores the therapeutic potential of nine selected medicinal plants (Passiflora incarnata, Withania somnifera, Glycyrrhiza glabra, Spinacia oleracea, Piper betle, Annona squamosa, Aegle marmelos, Matricaria chamomilla, Ocimum sanctum) and their phytoconstituents in mitigating inflammation and anxiety related to air pollution exposure. Through bibliometric analysis, systematic review, and meta-analysis, we evaluate their mechanisms of action, focusing on molecular pathways like cytokine modulation, NF-κB signaling, antioxidant defense, and neurophysiological regulation. The findings highlight the potential of these plants in addressing both systemic and neurological effects of pollution. However, challenges remain in standardizing dosages and conducting long-term clinical studies. Future research should prioritize dosage standardization, synergistic phytochemical interactions, and extensive clinical trials to optimize their therapeutic use in air pollution-related health issues.

Ashwagandha and Its Role in Stress Reduction, Hormonal Balance, and Athletic Recovery: An Evidence-Based Review

Weronika Ossowska, Maksymilian Czarnota, Wiktoria Ösztreicher · Journal of Education Health and Sport · 2025 · 4 citations

Introduction and Purpose: Ashwagandha (Withania somnifera) is a well-known adaptogenic herb used traditionally in Ayurvedic medicine. In recent years, it has attracted scientific interest for its potential to reduce stress, support hormonal balance, and improve recovery after physical exertion. Given the increasing use of herbal supplements among athletes and active individuals, this review aims to critically examine clinical evidence regarding the effects of ashwagandha supplementation on stress reduction, regulation of cortisol and testosterone levels, and enhancement of physical recovery. State of Knowledge: Current clinical studies suggest that ashwagandha may effectively lower cortisol levels, thereby supporting stress resilience in both mentally and physically demanding contexts. Several randomized controlled trials have reported improvements in perceived stress and anxiety, along with significant reductions in physiological stress markers. Additionally, ashwagandha supplementation has been associated with increases in testosterone levels, particularly in physically active men, which may contribute to improved strength, recovery, and hormonal stability. Some evidence also points to enhanced muscle recovery and decreased post-exercise fatigue, although findings vary depending on dosage, extract standardization, and study duration. Conclusion: Ashwagandha shows promising potential as a natural intervention to support psychological and physiological recovery in active populations. While findings are encouraging, further well-designed trials with larger sample sizes and standardized preparations are needed to confirm its long-term safety and efficacy.

Adjunctive Treatment with Rhodiola Crenulata in Patients with Chronic Obstructive Pulmonary Disease – A Randomized Placebo Controlled Double Blind Clinical Trial

Ming‐Lung Chuang, Tzu‐Chin Wu, Yau-Tung Wang +5 more · PLoS ONE · 2015 · 15 citations

UNLABELLED: Chronic obstructive pulmonary disease (COPD) is a low grade systemic inflammatory disease characterized by dyspnea and exercise intolerance even under standard therapy. Rhodiola crenulata (RC) has been shown to exert anti-inflammatory effects and to enhance exercise endurance, thereby having the potential to treat COPD. In this 12-week, randomized, double-blind, placebo-controlled clinical trial, 57 patients with stable moderate-to-severe COPD aged 70±8.8 years were given RC (250 mg twice/day) (n=38) or a placebo (250 mg twice/day) (n=19) in addition to their standard regimen. There were no significant differences in anthropometrics, quality of life, lung function, six-minute walk and incremental exercise tests between the two groups at enrollment. Over the 12 weeks, RC was well tolerated, significantly reduced triceps skin thickness (Δ=-1 mm, p=.04), change of FEV1 (4.5%, p=.03), and improved workload (Δ=10%, p=.01); although there were no significant differences in these factors between the two groups. However, there were significant between-group differences in tidal volume and ventilation-CO2-output ratio at peak exercise (both p=.05), which were significantly related to peak work rate (both p<.0001). RC tended to protect against acute exacerbation of COPD (p=.1) but not other measurements. RC did not improve the six-minute walk test distance but significantly improved tidal breathing and ventilation efficiency, most likely through improvements in work rate. Further studies with a larger patient population are needed in order to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02242461.

A Prospective, Randomized Double-Blind, Placebo-Controlled Study of Safety and Efficacy of a High-Concentration Full-Spectrum Extract of Ashwagandha Root in Reducing Stress and Anxiety in Adults

K. Chandrasekhar, Jyoti Kapoor, Sridhar Anishetty · Indian Journal of Psychological Medicine · 2012 · 323 citations

CONTEXT: Stress is a state of mental or emotional strain or tension, which can lead to underperformance and adverse clinical conditions. Adaptogens are herbs that help in combating stress. Ayurvedic classical texts, animal studies and clinical studies describe Ashwagandha as a safe and effective adaptogen. AIMS: The aim of the study was to evaluate the safety and efficacy of a high-concentration full-spectrum extract of Ashwagandha roots in reducing stress and anxiety and in improving the general well-being of adults who were under stress. SETTINGS AND DESIGN: Single center, prospective, double-blind, randomized, placebo-controlled trial. MATERIALS AND METHODS: A total of 64 subjects with a history of chronic stress were enrolled into the study after performing relevant clinical examinations and laboratory tests. These included a measurement of serum cortisol, and assessing their scores on standard stress-assessment questionnaires. They were randomized to either the placebo control group or the study drug treatment group, and were asked to take one capsule twice a day for a period of 60 days. In the study drug treatment group, each capsule contained 300 mg of high-concentration full-spectrum extract from the root of the Ashwagandha plant. During the treatment period (on Day 15, Day 30 and Day 45), a follow-up telephone call was made to all subjects to check for treatment compliance and to note any adverse reactions. Final safety and efficacy assessments were done on Day 60. STATISTICAL ANALYSIS: t-test, Mann-Whitney test. RESULTS: The treatment group that was given the high-concentration full-spectrum Ashwagandha root extract exhibited a significant reduction (P<0.0001) in scores on all the stress-assessment scales on Day 60, relative to the placebo group. The serum cortisol levels were substantially reduced (P=0.0006) in the Ashwagandha group, relative to the placebo group. The adverse effects were mild in nature and were comparable in both the groups. No serious adverse events were reported. CONCLUSION: The findings of this study suggest that a high-concentration full-spectrum Ashwagandha root extract safely and effectively improves an individual's resistance towards stress and thereby improves self-assessed quality of life.

Efficacy and safety of Shatavari root extract (Asparagus racemosus) for menopausal symptoms: a randomized, double-blind, three-arm, placebo-controlled study

John I. Ademola, Ashutosh Ajgaonkar, Tanisha Debnath +2 more · Frontiers in Reproductive Health · 2025 · 2 citations

Menopause brings hormonal changes that can significantly affect quality of life. Herbal remedies like Shatavari ( Asparagus racemosus Willd.) and Ashwagandha ( Withania somnifera L. Dunal) are Ayurvedic herbs traditionally used for hormonal balance and associated stress adaptation. The study evaluated the efficacy and safety of Shatavari root extract (SHT) alone and, in combination with Ashwagandha root extract (ARE-SHT), in women with menopausal symptoms. This was an 8-week, randomized, double-blind, placebo-controlled, multicentric study that enrolled 135 women aged 45–65 years. Participants were randomized into three groups: SHT ( n = 45) or an ARE-SHT ( n = 45), or a placebo (PL; n = 45). The primary outcome was evaluated by the change in the Menopause Rating Scale (MRS) score at weeks 4 and 8. Secondary outcomes were evaluated by changes in Perceived Stress Scale (PSS) score, Menopause-Specific Quality of Life Questionnaire (MENQOL) score, Profile of Mood States (POMS) score, hot flashes, and mood improvement. The serum hormonal assessments and safety evaluations (liver, renal, and thyroid function) were conducted at week 8. Baseline values were comparable among the groups. Significant improvements in MRS scores were observed in the ARE-SHT group compared to SHT [Week 4 and 8 ( p &amp;lt; 0.0001)] and PL [weeks 4 ( p = 0.01) and 8 ( p &amp;lt; 0.0001)], respectively. MENQOL scores improved numerically by week 8. Esteem-related affect ( p = 0.025) and mood improvement ( p = 0.008) showed significant changes between the groups. Normal hormonal levels were maintained. Mild adverse events were reported by four participants (loose stools and dizziness in the ARE-SHT group, nausea in the SHT monotherapy group, and headache in the PL group). Shatavari root extract was safe and effective; however, combined with Ashwagandha root extract demonstrated a promising option in managing menopausal symptoms and in enhancing overall health. Future studies with longer duration and larger sample sizes across defined menopausal stages are required to confirm and extend these findings. Clinical Trial Registration Clinicaltrials.gov , identifier [NCT06716554].

The effect of Withania somnifera (Ashwagandha) on mental health symptoms in individuals with mental disorders: systematic review and meta-analysis.

Marchi M, Grenzi P, Travascio A +7 more · BJPsych Open · 2025

Acute and chronic effects of <i>Rhaponticum carthamoides</i> and <i>Rhodiola rosea</i> extracts supplementation coupled to resistance exercise on muscle protein synthesis and mechanical power in rats

Rémi Roumanille, Barbara Vernus, Thomas Brioche +10 more · Journal of the International Society of Sports Nutrition · 2020 · 24 citations

BACKGROUND: Owing to its strength-building and adaptogenic properties, Rhaponticum carthamoides (Rha) has been commonly used by elite Soviet and Russian athletes. Rhodiola rosea (Rho) is known to reduce physical and mental fatigue and improve endurance performance. However, the association of these two nutritional supplements with resistance exercise performance has never been tested. Resistance exercise is still the best way to stimulate protein synthesis and induce chronic muscle adaptations. The aim of this study was to investigate the acute and chronic effects of resistance exercise coupled with Rha and Rho supplementation on protein synthesis, muscle phenotype, and physical performance. METHODS: For the acute study, fifty-six rats were assigned to either a trained control group or one of the groups treated with specific doses of Rha and/or Rho. Each rats performed a single bout of climbing resistance exercise. The supplements were administered immediately after exercise by oral gavage. Protein synthesis was measured via puromycin incorporation. For the chronic study, forty rats were assigned to either the control group or one of the groups treated with doses adjusted from the acute study results. The rats were trained five times per week for 4 weeks with the same bout of climbing resistance exercise with additionals loads. Rha + Rho supplement was administered immediately after each training by oral gavage. RESULTS: The findings of the acute study indicated that Rha and Rha + Rho supplementation after resistance exercise stimulated protein synthesis more than resistance exercise alone (p < 0.05). After 4 weeks of training, the mean power performance was increased in the Rha + Rho and Rha-alone groups (p < 0.05) without any significant supplementation effect on muscle weight or fiber cross-sectional area. A tendency towards an increase in type I/ type II fiber ratio was observed in Rha/Rho-treated groups compared to that in the trained control group. CONCLUSION: Rhodiola and Rhaponticum supplementation after resistance exercise could synergistically improve protein synthesis, muscle phenotype and physical performance.

Tinospora cordifolia (Giloy): An insight on the multifarious pharmacological paradigms of a most promising medicinal ayurvedic herb

Abhishek Gupta, Priyanka Gupta, G. K. Bajpai · Heliyon · 2024 · 45 citations

Medicinal herbs are being widely accepted as alternative remedies for preventing various diseases especially in India and other Asian countries. However, most plant-based herbal medicines are not yet being scientifically accepted worldwide. “Tinospora cordifolia (Willd.) Miers ex Hook.F. & Thomson”, one of the most promising plant species of Tinospora known as “Giloy” or Guduchi that is used in several traditional medicines in treating diseases e.g., metabolic and immune disorders, diabetes, heart diseases, cancer, and infectious diseases, has been widely investigated. Varieties of bioactive phytochemical constituents isolated from the stem, root and whole plant of T. cordifolia have been identified. In the last two decades, the diverse pharmacological activities of T. cordifolia have been continuously studied. Due to its therapeutic efficacy in immune modulation, it could be effective in viral and other diseases treatment as well. A medicinal plant could be well-suited not only for the treatment of target site but also for boosting the body's immune system. As an alternate source of medication, medicinal herbs are continuously showing better compatibility with the human body with minimal side effects than other therapies. Keeping this in mind, the present review highlights the pharmacological potential of T. cordifolia against various diseases.

Effects of Ashwagandha (Withania Somnifera) on stress and anxiety: A systematic review and meta-analysis.

Arumugam V, Vijayakumar V, Balakrishnan A +5 more · Explore (NY) · 2024

Safety and efficacy of Withania somnifera for anxiety and insomnia: Systematic review and meta-analysis.

Fatima K, Malik J, Muskan F +8 more · Hum Psychopharmacol · 2024

Pathophysiology and management of alzheimer’s disease: an overview

Ajit Kumar Thakur, Parul Kamboj, Kritika Goswami +1 more · Journal of Analytical & Pharmaceutical Research · 2018 · 135 citations

Alzheimer's disease (AD) is the sixth-leading reason of fatality and is 70% present in all cases of dementia. The global burden of AD is expected to accelerate from 26.6 million cases in 2006 to 106.8 million by 2050. The total assumed worldwide costs of dementia were US$ 604 billion in 2010, equivalent to 1% of the world's Gross domestic product (GDP). This review is focused on the overview of pathophysiology and management of AD. The sources for the literature search were PubMed, ScienceDirect, Scopus and Google Scholar. AD is generally considered as disorders related to intensify loss of neurons and synapses proceeds in distinct anatomical loci, resulting in different phenotypes. The pathophysiology of Alzheimer's disease is credited to a number of factors such as the cholinergic dysfunction, amyloid/tau toxicity and oxidative stress/ mitochondrial dysfunction. Apart from various therapeutic targets, biomarkers and pharmaco-therapies available; Herbal drugs, secondary metabolites and to the some extent non-pharmacological therapies are impending and potential candidates for the management of AD. Further studies are required to elaborate the detailed mechanism of Herbal drugs, secondary metabolites and non-pharmacological therapies for the management of AD.

Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (<i>Withania somnifera</i>) in Oligospermic Males: A Pilot Study

Vijay R. Ambiye, Deepak Langade, Swati Dongre +3 more · Evidence-based Complementary and Alternative Medicine · 2013 · 143 citations

Ashwagandha (Withania somnifera) has been described in traditional Indian Ayurvedic medicine as an aphrodisiac that can be used to treat male sexual dysfunction and infertility. This pilot study was conducted to evaluate the spermatogenic activity of Ashwagandha root extract in oligospermic patients. Forty-six male patients with oligospermia (sperm count < 20 million/mL semen) were enrolled and randomized either to treatment (n = 21) with a full-spectrum root extract of Ashwagandha (675 mg/d in three doses for 90 days) or to placebo (n = 25) in the same protocol. Semen parameters and serum hormone levels were estimated at the end of 90-day treatment. There was a 167% increase in sperm count (9.59 ± 4.37 × 10(6)/mL to 25.61 ± 8.6 × 10(6)/mL; P < 0.0001), 53% increase in semen volume (1.74 ± 0.58 mL to 2.76 ± 0.60 mL; P < 0.0001), and 57% increase in sperm motility (18.62 ± 6.11% to 29.19 ± 6.31%; P < 0.0001) on day 90 from baseline. The improvement in these parameters was minimal in the placebo-treated group. Furthermore, a significantly greater improvement and regulation were observed in serum hormone levels with the Ashwagandha treatment as compared to the placebo. The present study adds to the evidence on the therapeutic value of Ashwagandha (Withania somnifera), as attributed in Ayurveda for the treatment of oligospermia leading to infertility.

Therapeutic potential of &lt;i&gt;Withania somnifera&lt;/i&gt; (Ashwagandha): a comprehensive review of its phytochemical, pharmacological, and clinical applications

Martina Martorana, Anastasia Valentina Liga, Fabio Venturella · Journal of Biological Research - Bollettino della Società Italiana di Biologia Sperimentale · 2025 · 2 citations

Withania somnifera, commonly known as Ashwagandha or “Indian ginseng”, is one of the most important medicinal plants in Ayurvedic tradition, historically used as a rejuvenating tonic (rasayana) to promote vitality, stress resilience, and longevity. In recent years, scientific interest in Ashwagandha has grown significantly, particularly for its potential applications in managing stress, chronic fatigue, cognitive decline, and various inflammatory and metabolic disorders. Several preclinical and clinical studies suggest that Withania somnifera exhibits adaptogenic, anti-inflammatory, antioxidant, immunomodulatory, and neuroprotective activities, primarily attributed to the presence of withanolides, alkaloids, and flavonoids. However, despite encouraging findings, much of the current evidence stems from small-scale studies with heterogeneous methodologies, variable dosages, and inconsistencies in the standardization of extracts. Moreover, in some cases, clinical efficacy appears to fall short of expectations, with outcomes not always reaching statistical significance compared to placebo. This review critically examines the pharmacological properties and proposed mechanisms of action of Withania somnifera's bioactive compounds, while highlighting both its therapeutic potential and the methodological limitations present in current research. The review was conducted using databases such as PubMed, ScienceDirect, HerbMed, and Google Scholar. Although Ashwagandha remains a promising candidate in the context of integrative medicine, larger and longer-term clinical trials are needed to confirm its effectiveness and to better define its safety profile.

Effects of Withania somnifera (L.) Dunal (Ashwagandha) on cognitive and physical function in adults: a systematic review and meta-analysis.

Zhu X, Zeng Q, Lei Y +1 more · Front Pharmacol · 2026

Chemical Composition, Biological Activity, and Health-Promoting Effects of Withania somnifera for Pharma-Food Industry Applications

Javad Sharifi‐Rad, Cristina Quispe, Seyed Abdulmajid Ayatollahi +19 more · Journal of Food Quality · 2021 · 47 citations

The Withania genus comes from the Solanaceae family and includes around 23 species, spread over some areas of the Mediterranean, Asia, and East Africa. Widely used in traditional medicine for thousands of years, these plants are rich in secondary metabolites, with special emphasis on steroidal lactones, named withanolides which are used as ingredients in numerous formulations for a plethora of diseases, such as asthma, diabetes, arthritis, impotence, amnesia, hypertension, anxiety, stress, cancer, neurodegenerative, and cardiovascular diseases, and many others. Among them, Withania somnifera (L.) Dunal is the most widely addressed species from a pharmacological and agroindustrial point of view. In this sense, this review provides an overview of the folk uses, phytochemical composition, and biological activity, such as antioxidant, antimicrobial, anti-inflammatory, and cytotoxic activity of W. somnifera, although more recently other species have also been increasingly investigated. In addition, their health-promoting effects, i.e., antistress, anxiolytic, adaptogenic, antirheumatoid arthritis, chemoprotective, and cardiorespiratory-enhancing abilities, along with safety and adverse effects are also discussed.

Potent natural aphrodisiacs for the management of erectile dysfunction and male sexual debilities

Akhand Pratap Singh · Frontiers in Bioscience-Scholar · 2011 · 23 citations

The area of natural product research is rapidly progressing from traditional medicine to modern medicine having proper scientific basis of its usage. However, identifying the active constituent or the basis of its mechanism holds the key to synthesis of these drugs in the laboratory. Traditional Indian literature such as Ayurveda has listed several plant and animal based resources for treatment of almost every ailment. Erectile dysfunction and male sexual debilities are among the most explored areas in traditional medicine. A number of natural products, mostly plant based, have been claimed to cure erectile dysfunction and related male sexual debilities. These products often are aphrodisiac and have multi-fold effects on male reproductive system. This review aims at compiling the animal and plant based resources which bear promise of treating loss of libido and erectile dysfunction. A special emphasis is paid to find out scientific basis of their usage. The identification of potential resources could help undertake further studies to establish their possible mechanism of action; opening the doors to proper clinical trials for human use.

A standardized Ashwagandha root extract alleviates stress, anxiety, and improves quality of life in healthy adults by modulating stress hormones: Results from a randomized, double-blind, placebo-controlled study

Muhammed Majeed, Kalyanam Nagabhushanam, Lakshmi Mundkur · Medicine · 2023 · 38 citations

BACKGROUND: The coronavirus disease-2019 (COVID-19) pandemic has resulted in a surge in stress, anxiety, and depression worldwide. Ashwagandha, an ayurvedic adaptogen has been traditionally used to manage stress, anxiety, and general well-being. OBJECTIVE: We assessed the effect of Ashwagandha root extract (ARE-500 mg) standardized for 2.5% withanolides as per USP protocol with piperine (5 mg of 95% piperine) once daily for 60 days (12.5 mg withanolides/day) to alleviate stress and anxiety in healthy individuals with mild to moderate symptoms. METHODS: A randomized, double-blind, placebo-controlled study was conducted for 60 days using ARE (n = 27) and placebo (n = 27) once daily at night at Narayana Institute of Cardiac Sciences, Bangalore, and Vijaya Super Specialty Hospital, Nellore, in India. The objectives of this study were to assess an improvement in perceived stress scale (PSS), generalized anxiety disorder (GAD-7), quality of life (QOL), cognitive scores in the Cambridge Neuropsychological Test Automated Battery (CANTAB), changes in salivary cortisol, urinary serotonin, dopamine, serum levels of nitric oxide (NO), glutathione (GSH) and malondialdehyde (MDA) from baseline to end of the study. Safety was evaluated by laboratory parameters, and by monitoring any incidence of adverse events. RESULTS: 54 individuals were randomized and 50 of them completed the study. The PSS, GAD-7, and QOL scores improved significantly in all the participants taking ARE compared to the placebo. The CANTAB analysis revealed a significant improvement in multitasking, concentration, and decision taking time in ARE compared to placebo. ARE was also associated with a greater reduction in the morning salivary cortisol and an increase in urinary serotonin compared to placebo. Serum levels of NO, GSH, and MDA were not significantly different. Biochemical and hematological parameters remained in the normal range in all participants and ARE was well tolerated during the study. CONCLUSION: The results of the study suggest that ARE with 2.5% withanolides can effectively improve stress and anxiety by reducing cortisol and increasing serotonin in healthy individuals with mild to moderate symptoms.

Shoden promotes Relief from stress and anxiety: A randomized, double-blind, placebo-controlled study on healthy subjects with high stress levels

Deo Nidhi Mishra, M. Kumar · Heliyon · 2024 · 3 citations

Background: This randomized placebo-controlled study examined the effect of ashwagandha root and leaf extract 60 mg (AE60) and 120 mg (AE120) (35 % withanolide glycosides, Shoden) in physically healthy subjects with higher stress and anxiety. It is hypothesized that a low dose extract with higher withanolide glycosides would decrease cortisol and increase testosterone thereby reducing stress and anxiety. Methods: This parallel arm study recruited 60 subjects with an allocation ratio of 1:1:1 (AE60:AE120: placebo) for 60 days. Subjects who fulfilled the DSM -IV Criteria for generalized anxiety disorder (GAD) with a Hamilton Anxiety Rating Scale, HAMA score >20, and morning serum cortisol >25 mcg/dl were included in the study. The participants did not have depression symptoms and were screened using Montgomery-Asberg Depression Rating Scale. The primary outcome measure was HAMA and the secondary measures were morning serum cortisol, testosterone, perceived stress scale (PSS), clinical global impressions scale (CGI), and patient's global impression of change scale (PGIC). Results: After 60 days, significant differences were observed between the treatment groups and placebo. HAMA scores decreased by 59 % in both AE60 and AE120 groups compared to a negligible increase of 0.83 % in the placebo group (p < 0.0001). Morning serum cortisol levels decreased by 66 % in AE60 and 67 % in AE120, compared to a 2.22 % change in the placebo group (p < 0.0001). Testosterone levels increased by 22 % in AE60 and 33 % in AE120, compared to a 4 % increase in males in the placebo group (p < 0.0001). PSS scores decreased by 53 % in AE60 and 62 % in AE120, CGI-severity scores decreased by 72 % in AE60 and 68 % in AE120, and PGIC scores improved by 60 % in both AE60 and AE120 groups, all showing significant differences compared to the placebo group. Conclusion: Ashwagandha extract with 35 % withanolide glycosides (Shoden) at 60 mg and 120 mg was significantly effective in reduced morning serum cortisol and increasing total testosterone. Therefore, it can be recommended for reducing high stress and anxiety. Clinical trial registration: The study was prospectively registered in Clinical Trial Registry, India with registration number CTRI/2022/04/042133 [Registered on: April 25, 2022].

The Effect of Withania somnifera (Ashwagandha) Supplementation on Maximal Oxygen Uptake and Strength Endurance in Athletes: A Comprehensive Scientific Review

Anuradha Jindal, Vidhi Sharma, Dr. Mansingh Meena +1 more · International Journal of Research Publication and Reviews · 2025 · 0 citations

Withania somnifera (Ashwagandha) is a prominent adaptogenic herb from the Ayurvedic system of medicine with emerging, evidence-based applications as an ergogenic aid for athletes.This comprehensive review critically evaluates the body of controlled scientific literature on the effects of Ashwagandha supplementation on two key domains of athletic performance: cardiorespiratory endurance, measured by maximal oxygen uptake (VO2 max), and strength endurance, including maximal strength and muscular hypertrophy.Clinical evidence derived from randomized controlled trials and meta-analyses consistently demonstrates that chronic supplementation with standardized Ashwagandha root extract, typically at dosages of 600 mg per day, significantly improves VO2 max in both athletic and nonathletic populations.Similarly, when combined with structured resistance training, Ashwagandha supplementation has been shown to augment gains in muscle strength, muscle size, and power output, while also enhancing recovery.The ergogenic potential of Ashwagandha is attributed to a multifactorial mechanism of action, including the modulation of the hypothalamic-pituitary-adrenal (HPA) axis, reduction of serum cortisol, augmentation of endogenous testosterone production, enhancement of mitochondrial bioenergetics, and potent antioxidant and anti-inflammatory effects.Standardized root extracts are generally welltolerated and considered safe for short-term use (8-12 weeks) in healthy individuals.However, athletes must prioritize products with third-party anti-doping certification.This review synthesizes the current evidence, discusses the physiological mechanisms, and provides practical considerations for athletes, concluding that Ashwagandha is a promising natural supplement for enhancing physical performance and adaptation to training.Further research is warranted, particularly concerning long-term safety and efficacy in elite and female athletic cohorts.

Safety and Tolerability of <scp> <i>Withania somnifera</i> </scp> Root Extract in Healthy Male Participants: A Pilot Randomized, Double‐Blind, Placebo‐Controlled Clinical Trial

Narendra Vaidya, Ramshyam Agarwal, Pankaj Kshirsagar +5 more · Food Science & Nutrition · 2025 · 1 citations

ABSTRACT Withania somnifera (WS), also known as Ashwagandha in Ayurveda, is valued for its anti‐inflammatory, antioxidant, adaptogenic, and memory‐enhancing properties. This study assessed the safety of standardized Ashwagandha root extract in healthy adult participants over 180 days. A randomized, placebo‐controlled, double‐blind trial was conducted on 40 healthy adult participants (50–70 years), randomized 1:1 to receive 200 mg WS extract or placebo capsules twice daily for 180 days. Each WS capsule contained ≥ 5.00 mg of withanolides, standardized by HPLC‐PDA per USP‐NF monograph. Safety outcomes were assessed at screening and day 180. Hematological, hepatic, renal, and lipid profiles remained within normal ranges with no clinically significant changes compared to screening. Testosterone levels significantly increased (15.7%) in male participants in the WS group. Thyroid hormone levels, inflammatory marker (CRP), and NT‐pro BNP levels showed no adverse changes. CRP decreased by 51.1%, and NT‐pro BNP by 28.70% in the WS. Slight improvement in immunological markers (CD3, CD4, CD8) was also noted. The vital signs remained stable, with no clinical abnormalities detected on chest X‐ray or ECG. Anthropometric parameters were not clinically changed after treatment. Taken together, the study concluded that WS root extract capsules (200 mg twice daily for 6 months) were well‐tolerated and safe, with no adverse effects reported. This double‐blind, placebo‐controlled study with extended follow‐up provides a comprehensive evaluation of the long‐term safety profile of WS supplementation. Trial Registration: Clinical Trial Registry‐India (CTRI) approval number: CTRI/2023/11/059395

Recent Advancements in the Prevention and Treatment of Genetic and Non-Genetic Obesity: A Pharmacological Perspective of Review

Trilochan Satapathy, Laxmi Sahu, Renuka Verma +4 more · Journal of Drug Delivery and Therapeutics · 2025 · 1 citations

Obesity is a complicated, long-term condition caused by a combination of behavioural, environmental, genetic, and epigenetic factors. It is a significant risk factor for a number of metabolic conditions, such as cardiovascular disease, type 2 diabetes, and some types of cancer. New knowledge and treatment options for obesity prevention and treatment, especially in relation to its hereditary and non-genetic variants, have been made possible by recent developments in pharmacological research. Monogenic, syndromic, and polygenic forms of genetic obesity are frequently caused by mutations or polymorphisms that impact energy expenditure, appetite control, or fat storage processes. Novel pharmacotherapies have focused on important targets such proopiomelanocortin (POMC) neurons, the leptin signalling pathway, and the melanocortin-4 receptor (MC4R). Rare hereditary types of obesity may be treated with medications like setmelanotide, a selective MC4R agonist. Excessive calorie intake, physical inactivity, and psychological problems contribute to non-genetic (or lifestyle-related) obesity, which is still more common and is frequently treated with a mix of medication and lifestyle changes. Clinical trials have shown that recently licensed medications like tirzepatide and semaglutide, which work on the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) pathways, significantly improve metabolism and reduce body weight. The goal of this review is to present a thorough examination of the most recent pharmacological approaches to treating both hereditary and non-genetic obesity. It emphasizes how crucial combination therapy, new drug targets, and precision medicine will be in determining how obesity is treated and prevented in the future. Keywords: Lipid disorder, genetic obesity, non-genetic obesity, type 2 diabetes, setmelanotide, glucagon-like peptide-1

Current insights into transcriptional role(s) for the nutraceutical Withania somnifera in inflammation and aging

Praful Saha, Saiprasad Ajgaonkar, Dishant Maniar +3 more · Frontiers in Nutrition · 2024 · 25 citations

The health-beneficial effects of nutraceuticals in various diseases have received enhanced attention in recent years. Aging is a continuous process wherein physiological activity of an individual declines over time and is characterized by various indefinite hallmarks which contribute toward aging-related comorbidities in an individual which include many neurodegenerative diseases, cardiac problems, diabetes, bone-degeneration, and cancer. Cellular senescence is a homeostatic biological process that has an important function in driving aging. Currently, a growing body of evidence substantiates the connection between epigenetic modifications and the aging process, along with aging-related diseases. These modifications are now being recognized as promising targets for emerging therapeutic interventions. Considering that almost all the biological processes are modulated by RNAs, numerous RNA-binding proteins have been found to be linked to aging and age-related complexities. Currently, studies have shed light on the ability of the nutraceutical Withania somnifera (Ashwagandha) to influence RNA expression, stability, and processing, offering insights into its mechanisms of action. By targeting RNA-related pathways, Withania somnifera may exhibit promising effects in ameliorating age-associated molecular changes, which include modifications in gene expression and signaling networks. This review summarizes the potential role of Withania somnifera as a nutraceutical in modulating RNA-level changes associated with aging, encompassing both in vitro and in vivo studies. Taken together, the putative role(s) of Withania in modulation of key RNAs will provide insights into understanding the aging process and facilitate the development of various preventive and therapeutic strategies employing nutraceuticals for healthy aging.

Ecdysterone and Turkesterone—Compounds with Prominent Potential in Sport and Healthy Nutrition

Velislava Todorova, Stanislava Ivanova, Dzhevdet Chakarov +2 more · Nutrients · 2024 · 25 citations

The naturally occurring compounds ecdysterone and turkesterone, which are present in plants, including Rhaponticum carthamoides Willd. (Iljin), Spinacia oleracea L., Chenopodium quinoa Willd., and Ajuga turkestanica (Regel) Briq, are widely recognized due to their possible advantages for both general health and athletic performance. The current review investigates the beneficial biological effects of ecdysterone and turkesterone in nutrition, highlighting their roles not only in enhancing athletic performance but also in the management of various health problems. Plant-based diets, associated with various health benefits and environmental sustainability, often include sources rich in phytoecdysteroids. However, the therapeutic potential of phytoecdysteroid-rich extracts extends beyond sports nutrition, with promising applications in treating chronic fatigue, cardiovascular diseases, and neurodegenerative disorders.

Protective Effects of a Rhodiola Crenulata Extract and Salidroside on Hippocampal Neurogenesis against Streptozotocin-Induced Neural Injury in the Rat

Ze-qiang Qu, Yan Zhou, Yuan‐Shan Zeng +4 more · PLoS ONE · 2012 · 131 citations

Previously we have demonstrated that a Rhodiola crenulata extract (RCE), containing a potent antioxidant salidroside, promotes neurogenesis in the hippocampus of depressive rats. The current study was designed to further investigate the protective effect of the RCE on neurogenesis in a rat model of Alzheimer's disease (AD) induced by an intracerebroventricular injection of streptozotocin (STZ), and to determine whether this neuroprotective effect is induced by the antioxidative activity of salidroside. Our results showed that pretreatment with the RCE significantly improved the impaired neurogenesis and simultaneously reduced the oxidative stress in the hippocampus of AD rats. In vitro studies revealed that (1) exposure of neural stem cells (NSCs) from the hippocampus to STZ strikingly increased intracellular reactive oxygen species (ROS) levels, induced cell death and perturbed cell proliferation and differentiation, (2) hydrogen peroxide induced similar cellular activities as STZ, (3) pre-incubation of STZ-treated NSCs with catalase, an antioxidant, suppressed all these cellular activities induced by STZ, and (4) likewise, pre-incubation of STZ-treated NSCs with salidroside, also an antioxidant, suppressed all these activities as catalase: reduction of ROS levels and NSC death with simultaneous increases in proliferation and differentiation. Our findings indicated that the RCE improved the impaired hippocampal neurogenesis in the rat model of AD through protecting NSCs by its main ingredient salidroside which scavenged intracellular ROS.

Adaptogenic Botanicals with Emphasis on Rhodiola rosea and Withania somnifera

Rubén P. Machín, Miguel Florido, Ricardo Chirino +1 more · European Journal of Medicinal Plants · 2023 · 2 citations

This review addresses the issue of plant adaptogens, botanical products with remarkable anti-stress effects. These actions result from its ability to increase the non-specific organism's resistance process against multiple stressors (physical, chemical or biological). They are capable of exerting a normalizing effect on the human body, being both non-toxic effects and not influencing normal organic functions. Several plants with a complex phytochemical profile meet the criteria for being adaptogens. Many of them have been used in traditional medicine as tonic-vitalizing agents for centuries to treat various health conditions. This review briefly explains the organism's stress responses against stressors and the evolution of the adaptogenic concept from a historic perspective. A rational classification of adaptogens plants is formulated although it does not cover the full variability of botanical adaptogens. Nevertheless, summarizing data from two of the most important plant adaptogens, golden root (Rhodiola rosea) and Indian ginseng (Withania somnifera), are described. This includes their most deserving ethnomedicinal properties, the various families of compounds that constitute their complex phytochemical profiles, pharmacological activities along with putative mechanism of action responsible for some of their multifaceted biological actions, and the multi-therapeutic and health-promoting activities obtained from the most relevant clinical trials performed to date. Additionally, several relevant and current issues regarding the safety and toxicity of both widely used adaptogens are detailed. These include potential negative drugs interactions, putative contraindications and warnings in specific physiological statuses or health conditions. Finally, despite the overlapping activities against stress and stress-related health conditions some superior therapeutic benefits are tentatively assigned both to Withania somnifera and Rhodiola rosea taking into account the overall evidence of efficacy from pharmacological and clinical studies.