{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T02:43:16Z","timestamp":1790476996207,"version":"4.1.0"},"reference-count":210,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T00:00:00Z","timestamp":1778889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chinese Herbal Medicine Industry Innovation Team of Shandong Province Agricultural Technology System","award":["SDAIT-20-07"],"award-info":[{"award-number":["SDAIT-20-07"]}]},{"name":"Beijing Natural Science Foundation","award":["6252017"],"award-info":[{"award-number":["6252017"]}]},{"name":"2115 Talent Development Program of China Agricultural University","award":["00109015"],"award-info":[{"award-number":["00109015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Pyrrolizidine alkaloids (PAs), a category of naturally occurring secondary metabolites, are commonly found in various botanical sources. Accumulating evidence indicates that PAs and their biologically active metabolites can interact with cellular components and trigger a variety of toxic effects in animals and humans. Notably, PAs exhibit significant hepatotoxic potential via nutritional supplements, environmental dissemination, food chain contamination, and broader ecological pollution. In this review, we summarize PA-induced hepatotoxicity in humans and animals and the underlying molecular mechanisms. It involves oxidative stress, mitochondrial dysfunction, apoptosis, ER stress, inflammation, autophagy, and ferroptosis. Several key signaling pathways, such as nuclear factor-erythroid 2 related factor 2 (Nrf2), mitogen-activated protein kinase (MAPK), protein kinase RNA-like endoplasmic reticulum kinase (PERK), toll like receptor 4 (TLR4), nuclear factor kappa-B (NF-\u03baB), transforming growth factor beta (TGF-\u03b2), p53, farnesoid X receptor (FXR), and pregnane X receptor (PXR), are also implicated. Furthermore, this review discusses diagnostic approaches, metabolic activation pathways, and detoxification strategies targeting PA-induced liver injury. Collectively, this review provides a comprehensive understanding of the molecular basis of PA hepatotoxicity and underscores the urgent need for improved risk assessment, early diagnosis, and effective detoxification interventions to mitigate PA-related liver diseases in humans and animals.<\/jats:p>","DOI":"10.3390\/antiox15050635","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:02:27Z","timestamp":1779375747000},"page":"635","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pyrrolizidine Alkaloid-Induced Hepatotoxicity: A Narrative Review on Molecular Mechanisms and Detoxification Strategies"],"prefix":"10.3390","volume":"15","author":[{"given":"Yizhuo","family":"Fang","sequence":"first","affiliation":[{"name":"Innovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Innovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4677-0524","authenticated-orcid":false,"given":"Chongshan","family":"Dai","sequence":"additional","affiliation":[{"name":"Innovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9516-6270","authenticated-orcid":false,"given":"Zhihui","family":"Hao","sequence":"additional","affiliation":[{"name":"Innovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1039\/np9870400577","article-title":"Pyrrolizidine alkaloids","volume":"4","author":"Robins","year":"1987","journal-title":"Nat. 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