Rosehip (Rosa rugosa Thunb.) ethanol extract ameliorates liver fibrosis through upregulation of the PPAR signaling pathway

• RRE has no acute oral toxicity, and the MTD in mice is 46.14 g/kg. • RRE ameliorates collagen deposition, inflammation, and oxidative stress in mice with CCL 4 -induced liver fibrosis. • Transcriptome sequencing shows that genes regulated by RRE are associated with metabolism and collagen deposition pathways. • RRE ameliorates liver fibrosis by upregulating PPARγ, RXRα, and Perilipin 5 in the PPAR signaling pathway. The objective of this study was to examine the effect of rosehip ( Rosa rugosa Thunb.) ethanol extract (RRE) on liver fibrosis in mice and the underlying molecular mechanisms. RRE has no acute oral toxicity, and the MTD in mice is 46.14 g/kg. Histopathological analysis showed that RRE significantly ameliorated inflammation, necrosis, and apoptosis of hepatocytes and collagen deposition caused by CCl 4 . Further assays indicated that RRE significantly suppressed the production of MDA while markedly increasing the levels of SOD and GSH in the liver. The AST, ALT, IL-6, IL-1β, TNF-α, HA, LN, PCIII, and IVC levels in serum were decreased by RRE. Transcriptome analysis shows that RRE significantly upregulates the PPAR signaling pathway. The RT-q PCR results further confirmed the RRE up-regulating Pparγ , Rxrα , and Plin5 in the PPAR signaling pathway. The Western blot and immunohistochemical results indicate that RRE upregulated PPARγ, RXRα, and Perilipin 5 while downregulating α-SMA and COL1A1 expression. The results indicate that RRE can ameliorate liver fibrosis in mice by upregulating the PPAR signaling pathway.