背景:非酒精性脂肪性肝炎(NASH)对公共卫生保健系统造成了沉重负担,经济和社会。然而,目前还没有正式批准的NASH药物治疗.已经提出氧化应激和线粒体功能障碍在NASH病理进展中起重要作用。疏肝消脂(SG)配方,作为一种经典的草药配方,显示减弱NASH。
目的:本研究旨在探讨SG方治疗NASH的潜在机制。
方法:应用超高效液相色谱-高分辨质谱结合生物信息学分析探讨SG配方的治疗靶点和主要成分。此外,使用体内NASH模型来证实SG配方的治疗效果。进行分子对接分析和进一步验证实验以验证生物信息学分析的结果。
结果:体内实验证实,在高脂饮食(HFD)诱导的NASH模型中,SG配方可显著减轻肝脏病理进程并缓解氧化应激。超高效液相色谱-高分辨率质谱(UPLC-HRMS)结合生物信息学分析阐述了SG配方的组成成分,揭示了SG配方治疗NASH的线粒体调控机制。进一步的体内实验验证了SG配方可以通过修复线粒体的结构和功能来减轻氧化应激。这与调节线粒体自噬密切相关。
结论:总之,这项研究表明,SG公式,它可以通过调节线粒体来减弱NASH,并且可能是NASH的潜在药物疗法。
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.
OBJECTIVE: This study aimed to explore the potential mechanisms of SG formula treating NASH.
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.
CONCLUSIONS: In summary, this study demonstrated that SG formula, which could attenuate NASH by regulating mitochondria and might be a potential pharmacotherapy for NASH.