Fatty liver disease (FLD) may eventually progress to a wide-ranging spectrum, involving steatosis, liver cirrhosis and even hepatocellular carcinoma. The study aimed to explore the activity and underlying mechanism of quassinoid compound Bruceine A (BA), which was extracted from traditional Chinese medicine Brucea javanica (L.) Merr., against FLD in mice. C57BL/6 mice (n=60) were divided equally into: Control (Con), FLD, BA low-, medium-, and high-dose treatment groups. FLD was induced by receiving a high-fat diet (HFD) over a 16-week period and 1, 2 and 4 mg/kg BA was administered by intraperitoneal injection every 4 days. Our study demonstrated that BA treatment significantly ameliorated FLD symptom (P<0.05 vs. FLD model group), evidenced by reduced body weight, decreased serum lipid profile, elevated hepatic function and attenuated hepatic steatosis. Moreover, reduced reactive oxygen species (ROS) and malondialdehyde (MDA) overproduction were found in FLD mice with BA treatment (P<0.05 vs. FLD model group). More significantly, network pharmacology analysis identified that BA was likely to exert therapeutic effects on FLD by down-regulating chemokine-receptor 1 (CCR1) expression, and this finding was further validated through the following in vivo experiments. Mechanistically, we revealed that BA supplementation promoted autophagosome formation and regulated the expression of autophagy-related markers, including L3II/I, P62 and Beclin1 (P<0.05 vs. FLD model group). These findings suggested that BA-induced autophagy played a crucial role in alleviating the fatty liver condition. In conclusion, this study demonstrated that BA protected against induced FLD in mice through suppression of CCR1-dependent oxidative stress and activation of autophagic pathways, thereby providing novel therapeutic insights for the management of FLD.

To Cite This Article: Hu H, Liang S, Li Y, Liu J, Wu T and Tian Y, 2025. Bruceine A attenuates induced fatty liver disease by inhibiting CCR1 and activating autophagy in C57BL/6J mice. Pak Vet J, 45(3): 1403-1410. http://dx.doi.org/10.29261/pakvetj/2025.270