Background and Aims: Lian-He-Xiao-Zhi ointment (LHXZO) is an empirical formula, which has a significant therapeutic effect on metabolic associated fatty liver disease (MAFLD) in clinical practice. However, the precise underlying mechanisms remain unclear. The objective of this study is to elucidate the mechanisms through which the LHXZO ameliorates MAFLD, utilizing an animal model.
Methods: C57BL/6J mice (6-8 weeks old, male) were subjected to a high-fat diet (HFD) to induce a MAFLD model. Mice received either LHXZO decoction or control solution intragastrically daily for twelve weeks. Histological and serum analyses were used to assess the liver injury and disorders of glucolipid metabolism. Total RNAseq and pathway analyses were used to identify the potential signaling pathways modulated by LHXZO in the liver. The expression levels of key genes involved in regulating lipid metabolism and inflammation were validated by qRT-PCR or Western blot analysis. The impact on gut microbiota was assessed through 16S rRNA gene sequencing.
Results: LHXZO treatment significantly improved glucolipid metabolic disorders, liver injury and liver inflammation, evidenced by decreased serum levels of fasting blood glucose, free fatty acid, TG, AST, ALT, LPS and IL-1β. HE and Oil Red O staining also showed LHXZO treatment reduced lipid deposition in the liver. Meanwhile, LHXZO significantly reduced the body weight of MAFLD mice. LHXZO mitigated inflammation by downregulating TLR4, NF-KB, NLRP3, IL-1β and IL-18. In addition, LHXZO significantly upregulated the level of PPARa. Furthermore, LHXZO significantly modulated gut microbiota.
Conclusions: LHXZO effectively improve glucolipid metabolism, liver injury and inflammation in MAFLD, indicating its potential as a therapeutic agent for MAFLD. LHXZO's improvement of liver inflammation in MAFLD mice may be achieved by regulating PPARα or gut microbiota.
Keywords: MAFLD; PPARα; inflammation; gut microbiota
L. Nie: None. X. Yang: None. X. Zhou: None.
the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD, 035062005002-14), the special research project of Jiangsu Administration of traditional Chinese medicine (zt202105), and the Project Funded by Jiangsu Province Hospital of Chinese Medicine (kkzx01).
