Fragaria orientalis attenuates hepatic fibrosis through modulation of FXR/CYP7A1, ERK/p38 MAPK, and TLR4/MyD88/NF-κB signaling in rats

Abstract Objectives Fragaria orientalis Losinsk is widely used in Tibetan medicine to remove and eliminate yellow water, a symptom of visceral abscesses including hepatitis, suggesting that Fragaria orientalis may exert potential therapeutic benefits for liver conditions. This study aimed to elucidate the hepatoprotective mechanisms of Fragaria orientalis extract against hepatic fibrosis in rats, focusing on the FXR/CYP7A1, ERK/p38 MAPK, and TLR4/MyD88/NF-κB signaling pathways. Methods Chemical profiling was measured by UPLC-Q-TOF/MS, followed by HPLC fingerprint. Hepatic fibrosis was induced in rats treated with 40% CCl4. Subsequently, the anti-fibrotic effects of Fragaria orientalis involved in different signaling pathways were examined. Results Administration of Fragaria orientalis extract reduced serum levels of ALT, AST, ALP, TNF-α, IL-1β, and IL-6, as well as hepatic MDA, while increasing GSH-Px and SOD in liver homogenates. UPLC analysis identified key constituents, including quercetin-3-O-glucuronide and ellagic acid, contributing to its hepatoprotective profile. The extract modulated the FXR/CYP7A1, ERK/p38 MAPK, and TLR4/MyD88/NF-κB pathways, supporting its role in attenuating liver fibrosis. Conclusion In conclusion, these findings suggest that Fragaria orientalis possesses hepatoprotective effects against hepatic fibrosis, likely through modulating oxidative stress, inflammation, and bile acid regulation pathways.