Biomedicine & Pharmacotherapy (Dec 2023)

A classical herbal formula alleviates high-fat diet induced nonalcoholic steatohepatitis (NASH) via targeting mitophagy to rehabilitate dysfunctional mitochondria, validated by UPLC-HRMS identification combined with in vivo experiment

  • Mingtai Chen,
  • Furong Huang,
  • Bohao Chen,
  • Junli Kang,
  • Yijing Yao,
  • Mengnan Liua,
  • Yuanyuan Li,
  • Yaqin Li,
  • Tianran Zhou,
  • Deti Peng,
  • Lidan Luo,
  • Chunshan Wei,
  • Yufeng Xing,
  • Qibiao Wu,
  • Hua Zhou,
  • Guangdong Tong

Journal volume & issue
Vol. 168
p. 115831

Abstract

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Background: Nonalcoholic steatohepatitis (NASH) has caused a significant burden on public health care systems, the economy and society. However, there has still been no officially approved pharmacotherapy for NASH. It has been suggested that oxidative stress and mitochondrial dysfunction play vital roles in NASH pathological progression. Shugan Xiaozhi (SG) formula, as a kind of classical herbal formula, was shown to attenuate NASH. Purpose: This study aimed to explore the potential mechanisms of SG formula treating NASH. Study design and methods: Ultra-high-performance liquid chromatography-high resolution mass spectrometry combined with bioinformatics analysis was applied to explore the therapeutic targets and main components of SG formula. Moreover, in vivo NASH model was utilized to confirmed the therapeutic effects of SG formula. Molecular docking analysis and further validation experiments were conducted to verify the results of bioinformatics analysis. Results: The in vivo experiments confirmed SG formula significantly attenuated hepatic pathological progression and relieved oxidative stress in high-fat diet (HFD) induced - NASH model. Ultra-high-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) combined with bioinformatics analysis expounded the components of SG formula and revealed the mitochondrial regulation mechanism of SG formula treating NASH. Further in vivo experiments validated that SG formula could alleviate oxidative stress by rehabilitating the structure and function of mitochondria, which was strongly related to regulating mitophagy. Conclusion: In summary, this study demonstrated that SG formula, which could attenuate NASH by regulating mitochondria and might be a potential pharmacotherapy for NASH.

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