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Ethnopharmacological use of medicinal plants offers a rich resource for discovering novel hepatoprotective agents, particularly secondary metabolites including alkaloids, flavonoids, terpenoids, glycosides, tannins, and saponins that target key pathogenic processes such as oxidative stress, inflammation, fibrosis, apoptosis, and metabolic dysregulation. This review systematically integrates traditional knowledge with modern evidence from in\u00a0vitro, in\u00a0vivo, preclinical, and clinical studies to highlight plant\u2010derived phytoconstituents with demonstrated benefits across the spectrum of liver diseases, including clinically investigated agents such as silymarin, glycyrrhizin, curcumin, resveratrol, and ginsenosides. Mechanistic sections summarize disease progression from inflammation to fibrosis, cirrhosis, and hepatocellular carcinoma, and delineate how specific phytoconstituents modulate signaling pathways, redox homeostasis, lipid metabolism, and cell death programs, while pharmacokinetic data address absorption, distribution, metabolism, excretion, and strategies to overcome low oral bioavailability. The article also contrasts the limitations of current synthetic drugs with regulatory advances for botanical products across major agencies (FDA, EMA, WHO, and Asian regulators), and outlines methodological innovations including high\u2010throughput screening, cheminformatics, in silico docking, organoid and liver\u2010on\u2010chip models, and nanotechnology\u2010based delivery systems that can accelerate phytoconstituent\u2010driven drug development. Overall, this review provides a comprehensive framework that links ethnomedicinal use, experimental validation, regulatory context, and technological progress, and identifies priority phytoconstituents and research directions for translating plant\u2010based hepatoprotective agents into standardized, clinically effective therapies for liver disease.<\/jats:p>","DOI":"10.1002\/ptr.70383","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:41:51Z","timestamp":1781584911000},"page":"5441-5500","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Liver Disease and Plant\u2010Derived Phytoconstituents: From Ethnopharmacology to Modern Medicine"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1123-2806","authenticated-orcid":false,"given":"Bipindra","family":"Pandey","sequence":"first","affiliation":[{"name":"Department of Pharmacy Madan Bhandari Academy of Health Sciences  Hetauda Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sagun","family":"Kharel","sequence":"additional","affiliation":[{"name":"Department of Nursing Madan Bhandari Academy of Health Sciences  Hetauda Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjila","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Janamaitri Foundation Institute of Health Sciences Tribhuvan University  Lalitpur Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biswash","family":"Sapkota","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Madan Bhandari Academy of Health Sciences  Hetauda Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laxman","family":"Subedi","sequence":"additional","affiliation":[{"name":"School of Health and Allied Sciences, Pokhara University  Pokhara Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushil","family":"Panta","sequence":"additional","affiliation":[{"name":"School of Health and Allied Sciences, Pokhara University  Pokhara Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"e_1_2_20_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.02.128"},{"issue":"3","key":"e_1_2_20_3_1","first-page":"114","article-title":"Hepatoprotective Activity of Ethanolic and Ethyl Acetate Extracts of \n                     Sterculia setigera\n                   Against Carbon Tetrachloride Induced Hepatotoxicity in Albino Rats","volume":"1","author":"Abdelrahman T. 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