Ma Chuanrui, Wang Xinyu, Zhang Jing, Zhao Yun, Hua Yunqing, Zhang Chao, Zheng Guobin, Yang Guangyan, Guan Jianli, Li Huahuan, Li Meng, Kang Lin, Xiang Jiaqing, Fan Guanwei, Yang Shu
First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
Front Pharmacol. 2022 Jun 14;13:893336. doi: 10.3389/fphar.2022.893336. eCollection 2022.
Nonalcoholic fatty liver disease (NAFLD) is defined as liver disease in which more than 5% of hepatocytes are steatotic with little or no alcohol consumption. NAFLD includes benign nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). Importantly, NASH is an advanced progression of NAFL and is characterized by steatosis, hepatocyte ballooning, lobular inflammation, and fibrosis. However, to date, no drugs specifically targeting NAFLD have been approved by the FDA. Therefore, a new drug or strategy for NAFLD treatment is necessary. However, the pathogenesis of NAFLD is complex and no single-target drugs have achieved the desired results. Noticeably, traditional Chinese medicine formulations are a complex system with multiple components, multiple targets, and synergistic effects between components. The Ganweikang tablet is a compound formula based on traditional Chinese medicine theory and clinical experience. In this study, network pharmacology analysis indicates Ganweikang tablet as a candidate for NAFLD treatment. Furthermore, we evaluated the therapeutic effects of Ganweikang tablet on the NAFL and NASH and tried to clarify the underlying molecular mechanisms in animal models and cell experiments. As expected, Ganweikang tablet was found to improve NAFL and NASH by modulating inflammation, apoptosis, and fatty acid oxidation by inhibiting NFκB, caspase-8, and activating PPARα, which not only indicates that Ganweikang tablet as a drug candidate but also provides a theoretical basis of Ganweikang tablet for the treatment of NAFL and NASH.
非酒精性脂肪性肝病（NAFLD）被定义为在几乎不饮酒或不饮酒的情况下，超过5%的肝细胞发生脂肪变性的肝脏疾病。NAFLD包括良性非酒精性脂肪肝（NAFL）和非酒精性脂肪性肝炎（NASH）。重要的是，NASH是NAFL的一种进展期病变，其特征为脂肪变性、肝细胞气球样变、小叶炎症和纤维化。然而，迄今为止，美国食品药品监督管理局（FDA）尚未批准专门针对NAFLD的药物。因此，需要一种治疗NAFLD的新药或新策略。然而，NAFLD的发病机制复杂，单靶点药物并未取得理想效果。值得注意的是，中药制剂是一个具有多种成分、多个靶点且成分间具有协同作用的复杂体系。肝胃康片是基于中医理论和临床经验的复方制剂。在本研究中，网络药理学分析表明肝胃康片是治疗NAFLD的候选药物。此外，我们评估了肝胃康片对NAFL和NASH的治疗效果，并试图在动物模型和细胞实验中阐明其潜在的分子机制。正如预期的那样，发现肝胃康片通过抑制NFκB、半胱天冬酶 - 8并激活PPARα来调节炎症、细胞凋亡和脂肪酸氧化，从而改善NAFL和NASH，这不仅表明肝胃康片是一种候选药物，也为肝胃康片治疗NAFL和NASH提供了理论依据。
