Published online Feb 27, 2024. doi: 10.4254/wjh.v16.i2.264
Peer-review started: October 18, 2023
First decision: December 26, 2023
Revised: January 9, 2024
Accepted: February 1, 2024
Article in press: February 1, 2024
Published online: February 27, 2024
Processing time: 132 Days and 2.2 Hours
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.
To investigate the potential of YHG in alleviating carbon tetrachloride (CCl4)-induced liver fibrosis in mice.
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.
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.
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.
Core Tip: Yinhuang granule (YHG), a Chinese patent medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos, is traditionally employed for the management of tonsillitis, pharyngitis, as well as upper respiratory tract infections in clinical practice. Here, our study found that YHG effectively alleviated liver fibrosis in carbon tetrachloride-treated mice through various mechanisms, including the inhibition of hepatic stellate cells activation, reduction of inflammation, alleviation of liver oxidative stress damage by prompting nuclear factor erythroid 2-related factor 2 activation, and promotion of liver mitochondrial biogenesis. These findings substantiate the potential clinical use of YHG as a therapy for liver fibrosis.