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This metabolic barrier is the key defense line to resist the invasion of drugs and environmental poisons. There are significant differences in the structural function and toxic response mechanism of the metabolic barrier between the liver and kidney. This review explains the core composition and physiological function of the hepatorenal metabolic barriers respectively. It also systematically analyzes the specific mechanisms of toxic damage to these barriers. The core of liver injury is the destruction of hepatic sinus barrier, disorder of metabolic enzyme expression and bile excretion disorder. Renal injury focuses on glomerular filtration barrier injury, abnormal renal tubular transport function and renal interstitial inflammatory reaction. In this review, the specific protective value and intervention mechanism of natural products such as herbal components, single Chinese medicinal herbs and Chinese medicinal prescriptions on hepatorenal metabolic barrier damage were summarized. This provides targeted theoretical support for the development of hepatorenal protective drugs.<\/jats:p>","DOI":"10.3389\/fphar.2026.1763782","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T05:32:22Z","timestamp":1777872742000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Response mechanism of hepatorenal metabolic barrier function to drugs and environmental poisons and intervention strategy of natural products"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhen","family":"Li","sequence":"first","affiliation":[{"name":"Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Xie","sequence":"additional","affiliation":[{"name":"Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Che","family":"Xu","sequence":"additional","affiliation":[{"name":"Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1186\/s12967-022-03759-z","article-title":"Targeting HSP47 and HSP70: promising therapeutic approaches in liver fibrosis management","volume":"20","author":"Abd El-Fattah","year":"2022","journal-title":"J. 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