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Alterations in fatty acid metabolism have been associated with the pathogenesis of cisplatin-induced nephrotoxicity, yet the precise mechanisms remain unclear. Bavachin, a natural flavonoid, exhibits anti-inflammatory, antioxidant, and lipid metabolism-regulating properties, yet its role in mitigating cisplatin-induced nephrotoxicity via mitochondrial \u03b2-oxidation remains unexplored.\u00a0Mitofusin-2 (MFN2), a mitochondrial fusion protein, has emerged as a critical regulator of fatty acid oxidation (FAO) and lipid homeostasis. However, its role in cisplatin-induced nephrotoxicity has not been fully explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>C57\/6L mice were randomly divided into control, DMSO, cisplatin, and cisplatin\u2009+\u2009Bavachin groups. Blood urea nitrogen (BUN), serum creatinine (SCr), reactive-oxygen-species (ROS), lipid accumulation, and apoptosis were assessed. In vitro, the human proximal tubule epithelial cell line (HK-2) cells were treated with 20\u00a0\u00b5M cisplatin with or without bavachin. ROS production was detected by the DCFH-DA, lipid deposition was detected by oil red O staining, and MFN2, carnitine palmitoyltransferase 1a (CPT1a) were detected by Western blot (WB).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with the cisplatin group, bavachin treatment reduced BUN (21.8%) and SCr (78.7%) in the cisplatin group, accompanied by improvements in renal pathological changes, lipid deposition, and apoptosis. In addition, bavachin up-regulated the expression of MFN2 and CPT1a, while decreasing the cisplatin-induced ROS overproduction. Similar results were found in vitro. Notably, the mitochondrial FAO has been increased in HK-2 cells treated with bavachin. Further, MFN2 siRNA partially reversed these protective effects, accompanied by decreased CPT1a expression and exacerbated lipid deposition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study is the first to confirm MFN2 as a target for renal protection by bavachin. Mechanistically, Bavachin alleviated cisplatin-induced lipid accumulation and apoptosis by upregulating MFN2 expression, which activated CPT1a to promote mitochondrial FAO. These results will provide a new strategy for cisplatin-based cancer therapy and the reduction of its nephrotoxicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s10020-025-01283-6","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T07:31:23Z","timestamp":1749627083000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Bavachin ameliorates cisplatin-induced nephrotoxicity by enhancing mitochondrial \u03b2-oxidation and lipid metabolism through MFN2"],"prefix":"10.1186","volume":"31","author":[{"given":"Shilu","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenrui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"issue":"9","key":"1283_CR1","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.3390\/molecules29091927","volume":"29","author":"SA Abass","year":"2024","unstructured":"Abass SA, Elgazar AA, El-Kholy SS, El-Refaiy AI, Nawaya RA, Bhat MA, et al. 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