Yinhuang granule alleviates carbon tetrachloride-induced liver fibrosis in mice and its mechanism

Hao Ouyang; Hui Miao; Zhen Li; Duan Wu; Si-Cheng Gao; Yao-Yao Dai; Xiao-Di Gao; Hai-Sheng Chai; Wei-Ye Hu; Jun-Feng Zhu

doi:10.4254/wjh.v16.i2.264

Yinhuang granule alleviates carbon tetrachloride-induced liver fibrosis in mice and its mechanism

World J Hepatol. 2024 Feb 27;16(2):264-278. doi: 10.4254/wjh.v16.i2.264.

Authors

Hao Ouyang¹, Hui Miao², Zhen Li¹, Duan Wu¹, Si-Cheng Gao¹, Yao-Yao Dai¹, Xiao-Di Gao¹, Hai-Sheng Chai¹, Wei-Ye Hu¹, Jun-Feng Zhu³

Affiliations

¹ Department of Liver, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
² State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 201203, China.
³ Department of Liver, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. zhujftongling@163.com.

Abstract

Background: Liver fibrosis is a formidable global medical challenge, with no effective clinical treatment currently available. Yinhuang granule (YHG) is a proprietary Chinese medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos. It is frequently used for upper respiratory tract infections, pharyngitis, as well as acute and chronic tonsillitis.

Aim: To investigate the potential of YHG in alleviating carbon tetrachloride (CCl₄)-induced liver fibrosis in mice.

Methods: To induce a hepatic fibrosis model in mice, this study involved intraperitoneal injections of 2 mL/kg of CCl₄ twice a week for 4 wk. Meanwhile, liver fibrosis mice in the low dose of YHG (0.4 g/kg) and high dose of YHG (0.8 g/kg) groups were orally administered YHG once a day for 4 wk. Serum alanine/aspartate aminotransferase (ALT/AST) activity and liver hydroxyproline content were detected. Sirius red and Masson's trichrome staining assay were conducted. Real-time polymerase chain reaction, western-blot and enzyme-linked immunosorbent assay were conducted. Liver glutathione content, superoxide dismutase activity level, reactive oxygen species and protein carbonylation amount were detected.

Results: The administration of YHG ameliorated hepatocellular injury in CCl₄-treated mice, as reflected by decreased serum ALT/AST activity and improved liver histological evaluation. YHG also attenuated liver fibrosis, evident through reduced liver hydroxyproline content, improvements in Sirius red and Masson's trichrome staining, and lowered serum hyaluronic acid levels. Furthermore, YHG hindered the activation of hepatic stellate cells (HSCs) and ameliorated oxidative stress injury and inflammation in liver from CCl₄-treated mice. YHG prompted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the expression of Nrf2-dependent downstream antioxidant genes. In addition, YHG promoted mitochondrial biogenesis in liver from CCl₄-treated mice, as demonstrated by increased liver adenosine triphosphate content, mitochondrial DNA levels, and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and nuclear respiratory factor 1.

Conclusion: YHG effectively attenuates CCl₄-induced liver fibrosis in mice by inhibiting the activation of HSCs, reducing inflammation, alleviating liver oxidative stress damage through Nrf2 activation, and promoting liver mitochondrial biogenesis.

Keywords: Hepatic stellate cells; Inflammation; Liver fibrosis; Nuclear factor erythroid 2-related factor 2; Oxidative injury; Yinhuang granule.