Quzhi formula improves liver fibrosis related to metabolic dysfunction associated steatohepatitis by regulating the ITGB6/IL23A/STAT3 pathway

Abstract

Abstract: Objective The purpose of this study was to explore whether Quzhi formula has the effect of improving metabolic dysfunction associated steatohepatitis (MASH) related fibrosis and the internal mechanism of its efficacy. Methods LX2 cells were starved for 24 hours with fetal bovine serum-free DMEM medium overnight and then treated with TGF-β1 at 10 ng/mL (Abcam, ab50036). Finally, the cells were treated with serum-free DMEM medium containing 200μg/mL Quzhi formula. The cytotoxicity of Quzhi formula was detected by cell counting kit-8 assay, then western blotting, quantitative reverse transcription-polymerase chain reaction and immunofluorescence were performed to measure whether Quzhi formula reversed the activation of LX-2 induced by TGF-β1. For in vivo experiment, C57BL/6 SPF mice aged 6 weeks were randomly divided into 3 groups: control group, MASH group and Quzhi formula group. The MASH group and Quzhi formula group were fed diets containing 62% kcal fat and 0.1% methionine and choline deficiency for 3 weeks. Mice in the control group and MASH group were administrated with normal saline, and mice in the Quzhi formula group were administrated with Quzhi formula (10g/kg/d). After 9 weeks, the mice were euthanized, plasma and liver tissues were collected, and the effect of Quzhi formula was analyzed. Results The animal experiment proved that the lipid accumulation and liver fibrosis in MASH mice could be alleviated by Quzhi formula. Cell experiments demonstrated that Quzhi formula reversed TGF-β1 induced LX-2 activation by regulating ITGB6/IL23A/STAT3 signaling pathway. In addition, STAT3 inhibitors also reversed LX-2 activation induced by TGF-β1, which further demonstrated that Quzhi formula improves MASH related fibrosis through the above pathway. Conclusion Quzhi formula can not only improve MASH steatosis, but also alleviate MASH related fibrosis. It is suggested that Quzhi formula can be used as a new drug to treat MASH.

Key words: Quzhi formula, MASLD, MASH, Liver fibrosis

CHEN Hui-jie, PENG Zhou, ZHANG Qin. Quzhi formula improves liver fibrosis related to metabolic dysfunction associated steatohepatitis by regulating the ITGB6/IL23A/STAT3 pathway[J]. Chinese Hepatolgy, 2025, 30(5): 675-682.

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