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Ginsenoside Rh2 from <jats:italic>Panax ginseng<\/jats:italic> has been shown to protect against CDDP\u2010induced nephrotoxicity in vivo, but its pharmacological effect on renal tubular epithelial cells is not clearly understood. This study examined the molecular mechanisms underlying the nephroprotective effects of Rh2 on CDDP\u2010induced HK\u20102 cells and acute kidney injury (AKI) mice. As a result of Rh2 treatment, CDDP\u2010induced HK\u20102 cells showed increased cell viability and reduced lactate dehydrogenase release. Moreover, Rh2 ameliorated CDDP\u2010induced mitochondrial membrane potential, increased antioxidant enzyme activities, and reduced pro\u2010inflammatory cytokine expression to reduce damage. Rh2 inhibited apoptosis and enhanced the antioxidant capacity of HK\u20102 cells by reducing proteins associated with endoplasmic reticulum (ER) stress, as well as by attenuating tunicamycin\u2010induced ER stress. In addition, treatment of CDDP\u2010induced AKI mice with Rh2 substantially reduced blood urea nitrogen and serum creatinine levels, attenuated histological damage of kidney. Further, Rh2 also improved kidney function by inhibiting ER stress to support in vitro findings. These results consistently demonstrated that Rh2 protects renal tubular epithelial cells from CDDP\u2010induced nephrotoxicity and apoptosis by restoring ER homeostasis, which might suggest a therapeutic potential and providing new insights into AKI alternative therapies.<\/jats:p>","DOI":"10.1002\/jbt.23768","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T07:45:56Z","timestamp":1721202356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Effects of ginsenoside Rh2 on cisplatin\u2010induced nephrotoxicity in renal tubular epithelial cells by inhibiting endoplasmic reticulum stress"],"prefix":"10.1002","volume":"38","author":[{"given":"Lianping","family":"Wang","sequence":"first","affiliation":[{"name":"School of Life Sciences Jilin University  Changchun China"},{"name":"School of Traditional Chinese Medicine Jilin Agricultural Science and Technology University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogang","family":"Hao","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Changchun University of Chinese Medicine Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangxin","family":"Li","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Changchun University of Chinese Medicine Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1805-670X","authenticated-orcid":false,"given":"Qingjie","family":"Li","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Changchun University of Chinese Medicine Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuexun","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences Jilin University Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,17]]},"reference":[{"issue":"4","key":"e_1_2_10_2_1","first-page":"1","volume":"12","author":"Juncos L. 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