{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:45:32Z","timestamp":1785908732905,"version":"3.56.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020374","name":"Ministry of AYUSH, Government of India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020374","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"\n Background<\/jats:title>\n \n Withania somnifera<\/jats:italic>\n (Ashwagandha) is a widely used medicinal plant known for its neuroprotective, hepatoprotective, fertility-enhancing, and anti-inflammatory properties. Although it has a long history of use in traditional medicine, a detailed understanding of its phytochemical constituents and associated biological activities remains limited.\n <\/jats:p>\n <\/jats:sec>\n \n Aim<\/jats:title>\n \n To perform comprehensive metabolomic profiling of\n Withania somnifera<\/jats:italic>\n and identify its major bioactive secondary metabolites, with a focus on compounds contributing to neuroprotection, liver health, reproductive support, and inflammation modulation.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Root extracts of Withania somnifera (Ashwagandha) were subjected to methanol-based organic phase extraction followed by LC\u2013MS\/MS analysis, resulting in the characterization of 1,020 metabolites. Among these, 1,010 compounds were classified as putatively annotated (MSI Level 2\/3 annotations) metabolites based on MS1 data, while 10 highly abundant metabolites were further confirmed by MS\/MS fragmentation and assigned MSI Level 2 annotations. Relative abundance analysis was performed to determine the predominant phytochemical constituents of the extract. Key metabolites identified through this approach were subsequently correlated with the known pharmacological properties of Ashwagandha, including its immunomodulatory, anti-inflammatory, antioxidant, adaptogenic, and neuroprotective effects.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The analysis identified a diverse array of secondary metabolites, many present at low individual abundance (\n \n \n \n <<\/mml:mo>\n 0.30<\/mml:mn>\n %<\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n ). Notable compounds included the alkaloids Gentianaine (\n \n \n \n 8.44<\/mml:mn>\n %<\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n ) and Sauroxine (\n \n \n \n 2.94<\/mml:mn>\n %<\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n ), phenolics such as Mulberrofuran A (\n \n \n \n 14.58<\/mml:mn>\n %<\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n ) and Sulphuretin (\n \n \n \n 9.61<\/mml:mn>\n %<\/mml:mo>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n ), and terpenoids including Pinocarvone and Ergosterol. (% of total annotated metabolites) These compounds were associated with anti-oxidative, neuro-regenerative, hepatoprotective, and anti-inflammatory effects. Additional metabolites, including Gomphrenin-I, Sitosterol, Pfaffic acid, and\n \n \n \n \u03b2<\/mml:mi>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:inline-formula>\n -Carotene, were linked to reproductive health. Embelin and Kievitone were noted for their potential roles in enhancing oxidative stress responses. Despite the low abundance of individual compounds, the overall metabolite profile suggests substantial synergistic bioactivity.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Metabolomic profiling of\n Withania somnifera<\/jats:italic>\n reveals a rich composition of bioactive secondary metabolites with potential roles in neuroprotection, hepatoprotection, antioxidant defense, and reproductive support. These findings support its traditional use and highlight its potential for modern therapeutic applications in promoting stress resilience, vitality, and overall wellbeing.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmolb.2026.1796983","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:55:31Z","timestamp":1785905731000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolomic profiling of Ashwagandha (Withania somnifera): linking bioactive compounds to functional therapeutic roles"],"prefix":"10.3389","volume":"13","author":[{"given":"Gaurav","family":"Tripathi","sequence":"first","affiliation":[{"name":"Departments of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasundhra","family":"Bindal","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanju","family":"Yadav","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manisha","family":"Yadav","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Sharma","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushmita","family":"Pandey","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipul","family":"Sharma","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nupur","family":"Sharma","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babu","family":"Mathew","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yash","family":"Magar","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shvetank","family":"Sharma","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv Kumar","family":"Sarin","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Institute of Liver and Biliary Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaswinder Singh","family":"Maras","sequence":"additional","affiliation":[{"name":"Departments of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences","place":["New Delhi, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.3390\/nu15051107","article-title":"Polyphenols mediate neuroprotection in cerebral ischemic Stroke-An update","volume":"15","author":"Abdelsalam","year":"2023","journal-title":"Nutrients"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1084757","DOI":"10.3389\/fphar.2023.1084757","article-title":"The immunomodulatory role of withania somnifera (L.) dunal in inflammatory diseases","volume":"14","author":"Alanazi","year":"2023","journal-title":"Front. Pharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1111\/jdv.19805","article-title":"Multi-omics analysis identifies potential microbial and metabolite diagnostic biomarkers of bacterial vaginosis","volume":"38","author":"Challa","year":"2024","journal-title":"J. Eur. Acad. Dermatol Venereol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s00424-021-02640-0","article-title":"(-)-Epicatechin and cardiometabolic risk factors: a focus on potential mechanisms of action","volume":"474","author":"Hid","year":"2022","journal-title":"Pflugers Arch."},{"key":"B5","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1021\/acs.jnatprod.8b00592","article-title":"Isoquinoline alkaloids from Berberis vulgaris as potential lead compounds for the treatment of Alzheimer's Disease","volume":"82","author":"Hostalkova","year":"2019","journal-title":"J. Nat. Prod."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1855","DOI":"10.1007\/s12298-020-00859-2","article-title":"Phytochemical analysis, antioxidant activities and optimized extraction of embelin from different genotypes of embelia ribes burm f.: a woody medicinal climber from Western ghats of India","volume":"26","author":"Kamble","year":"2020","journal-title":"Physiol. Mol. Biol. Plants"},{"key":"B7","doi-asserted-by":"publisher","first-page":"4170","DOI":"10.3390\/nu14194170","article-title":"A mulberry component, prevents SARS-CoV-2 infection by blocking the interaction between SARS-CoV-2 spike protein S1 receptor-binding domain and human angiotensin-converting enzyme 2 receptor","volume":"14","author":"Kim","year":"2022","journal-title":"Nutrients"},{"key":"B8","doi-asserted-by":"publisher","first-page":"291","DOI":"10.2147\/JEP.S407906","article-title":"Efficacy and anti-inflammatory activity of ashwagandha sustained-release formulation on depression and anxiety induced by chronic unpredictable stress: in vivo and in vitro studies","volume":"15","author":"KrishnaRaju","year":"2023","journal-title":"J. Exp. Pharmacol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"10364","DOI":"10.1021\/jf1017719","article-title":"Structural identification and bioactivities of red-violet pigments present in Basella Alba fruits","volume":"58","author":"Lin","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e0440","DOI":"10.1097\/HC9.0000000000000440","article-title":"Circulating bacterial peptides and linked metabolomic signatures are indicative of early mortality in pediatric cirrhosis","volume":"8","author":"Mathew","year":"2024","journal-title":"Hepatol. Commun."},{"key":"B11","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1615\/IntJMedMushrooms.v19.i2.10","article-title":"Ergosterol peroxide: a mushroom-derived compound with promising biological Activities-A review","volume":"19","author":"Merdivan","year":"2017","journal-title":"Int. J. Med. Mushrooms"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.3390\/pharmaceutics15041057","article-title":"Ashwagandha (withania somnifera)-Current research on the health-promoting activities: a narrative review","volume":"15","author":"Mikulska","year":"2023","journal-title":"Pharmaceutics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.jtcme.2016.12.013","article-title":"Medicinal, biological and phytochemical properties of gentiana species","volume":"7","author":"Mirzaee","year":"2017","journal-title":"J. Tradit. Complement. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1002\/anie.201509379","article-title":"Bio-based polyketones by selective ring-opening radical polymerization of alpha-pinene-derived pinocarvone","volume":"55","author":"Miyaji","year":"2016","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.3390\/life12101502","article-title":"Ameliorative effect of D-Carvone against hepatic ischemia-reperfusion-induced injury in rats","volume":"12","author":"Mohamed","year":"2022","journal-title":"Life (Basel)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.70128","article-title":"Effects of ashwagandha on reproductive health: a systematic review of sex\u2010specific hormonal and fertility outcomes","author":"Roy","year":"2025","journal-title":"Phytotherapy Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e6466","DOI":"10.7759\/cureus.6466","article-title":"Adaptogenic and anxiolytic effects of ashwagandha root extract in healthy adults: a double-blind, randomized, placebo-controlled clinical study","volume":"11","author":"Salve","year":"2019","journal-title":"Cureus"},{"key":"B18","doi-asserted-by":"publisher","first-page":"101051","DOI":"10.1016\/j.xpro.2021.101051","article-title":"Global metabolome profiling of COVID-19 respiratory specimen using high-resolution mass spectrometry (HRMS)","volume":"3","author":"Sharma","year":"2022","journal-title":"Star. Protoc."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.3350\/cmh.2024.0554","article-title":"Plasma lipidomics and fungal peptide-based community analysis identifies distinct signatures for early mortality in acute liver failure","volume":"31","author":"Sharma","year":"2024","journal-title":"Clin. Mol. Hepatol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1080\/10408398.2020.1822277","article-title":"Betanin as a multipath oxidative stress and inflammation modulator: a beetroot pigment with protective effects on cardiovascular disease pathogenesis","volume":"62","author":"Silva","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"B21","doi-asserted-by":"publisher","first-page":"208","DOI":"10.4314\/ajtcam.v8i5S.9","article-title":"An overview on ashwagandha: a rasayana (Rejuvenator) of ayurveda","volume":"8","author":"Singh","year":"2011","journal-title":"Afr. J. Tradit. Complement. Altern. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.bbrc.2010.08.014","article-title":"Sulfuretin attenuates allergic airway inflammation in mice","volume":"400","author":"Song","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B23","doi-asserted-by":"publisher","first-page":"748014","DOI":"10.3389\/fmolb.2021.748014","article-title":"Baseline plasma metabotype correlates with direct-acting antiviral therapy nonresponse for HCV in HIV-HCV coinfected patients","volume":"8","author":"Tripathi","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1021\/np800151v","article-title":"Sauroine, an alkaloid from huperzia saururus with activity in wistar rats in electrophysiological and behavioral assays related to memory retention","volume":"72","author":"Vallejo","year":"2009","journal-title":"J. Nat. Prod."},{"key":"B25","doi-asserted-by":"publisher","first-page":"105913","DOI":"10.1016\/j.phrs.2021.105913","article-title":"Machine learning enables discovery of gentianine targeting TLR4\/NF-\u03baB pathway to repair ischemic stroke injury","volume":"173","author":"Wang","year":"2021","journal-title":"Pharmacol. Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"11852","DOI":"10.3390\/ijerph191911852","article-title":"Effects of acute ashwagandha ingestion on cognitive function","volume":"19","author":"Xing","year":"2022","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1111\/liv.15858","article-title":"Comparative metabolome analysis reveals higher potential of haemoperfusion adsorption in providing favourable outcome in ACLF patients","volume":"44","author":"Yadav","year":"2024","journal-title":"Liver Int."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2026.1796983\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:55:42Z","timestamp":1785905742000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2026.1796983\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":27,"alternative-id":["10.3389\/fmolb.2026.1796983"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2026.1796983","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]},"article-number":"1796983"}}