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 - 11/11/23
, Hua Zhou f, ⁎ , Guangdong Tong a, b, c, ⁎ Abstract |
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.
Le texte complet de cet article est disponible en PDF.Highlights |
• | In vivo experiments demonstrated that SG formula could improve the serum levels of AST, ALT, TNF-α, and IL-6, reduce the serum levels of TC and TG, and attenuate hepatic steatosis, lobular inflammation, hepatocellular ballooning and fibrosis in HFD-induced NASH model mice. |
• | Ultra-high-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) identified 41 components of SG formula. |
• | The results of network pharmacology analysis revealed the mitochondrial regulation mechanism of SG formula treating NASH. |
• | Further experiment validated that the therapeutic effect of SG formula on NASH was strongly related to regulating BNIP3/BNIP3L mediated mitophagy. |
Abbreviations : ALT, AP, ASS, AST, BS, CAP, CAT, CE, CH, DDA, DH, ESI, FL, GC, GO, GSH, H&E, HCD, HFD, HFS, HY, IL-6, JMZ, KEGG, LC3, MDA, NAFL, NAFLD, NASH, NASH, NWA, p62, PB, PDB, PPI, PVDF, ROS, SG, SOD, SZ, TC, CHM, TEM, TG, TNF-α, TR, UPLC-HRMS, YC, ZL, ZS, ZX, ZZ
Keywords : Herbal medicine, Nonalcoholic steatohepatitis, Mitochondria, Bioinformatics analysis, UPLC-HRMS
Plan
Vol 168
Article 115831- décembre 2023 Retour au numéro
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