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Its progression is characterized by persistent hepatic damage and gradual loss of liver function, which may ultimately lead to fibrosis, cirrhosis, and liver failure. However, currently available hepatoprotective drugs still present several limitations, such as insufficient target specificity, limited therapeutic efficacy, and potential adverse effects, highlighting the need for safer and more effective alternatives. Based on a comprehensive search of databases including PubMed, Web of Science, China National Knowledge Infrastructure and Google Scholar, this review summarizes the pathogenic mechanisms of major liver injury types and the therapeutic potential of natural alkaloids. As key secondary metabolites of medicinal plants, alkaloids exhibit structural diversity, potent bioactivities, and favorable safety profiles. Increasing evidence suggests that natural alkaloids exert hepatoprotective effects through multi-target and multi-pathway mechanisms, including the regulation of oxidative stress, inflammation, lipid metabolism, and cell death. These findings highlight their promising potential for the prevention and treatment of liver injury and provide a theoretical basis for the development of novel hepatoprotective agents.<\/jats:p>","DOI":"10.3390\/biom16060815","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:08:02Z","timestamp":1780535282000},"page":"815","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural Alkaloids Against Liver Injury: Mechanistic Insights and Multi-Target Therapeutic Potential"],"prefix":"10.3390","volume":"16","author":[{"given":"Yating","family":"Xiao","sequence":"first","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirui","family":"Tian","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Cui","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Cai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxin","family":"Jin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5564-4610","authenticated-orcid":false,"given":"Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Ji","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"Devarbhavi","year":"2023","journal-title":"J. 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