Zhang Peiguang, Cao Jieqiong, Liang Xujing, Su Zijian, Zhang Bihui, Wang Zhenyu, Xie Junye, Chen Gengrui, Chen Xue, Zhang Jinting, Feng Yanxian, Xu Qin, Song Jianping, Hong An, Chen Xiaojia, Zhang Yibo
Department of Cell Biology, College of Life Science and Technology, Jinan University; State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University; National Engineering Research Center of Genetic Medicine; Guangdong Provincial Key Laboratory of Bioengineering Medicine; Guangdong Provincial Biotechnology Drug & Engineering Technology Research Center, Jinan University, Guangzhou 510632, China.
Department of Infectious Disease, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
Acta Biochim Biophys Sin (Shanghai). 2024 Apr 25;56(4):621-633. doi: 10.3724/abbs.2024025.
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with a global prevalence of 25%. Patients with NAFLD are more likely to suffer from advanced liver disease, cardiovascular disease, or type II diabetes. However, unfortunately, there is still a shortage of FDA-approved therapeutic agents for NAFLD. Lian-Mei-Yin (LMY) is a traditional Chinese medicine formula used for decades to treat liver disorders. It has recently been applied to type II diabetes which is closely related to insulin resistance. Given that NAFLD is another disease involved in insulin resistance, we hypothesize that LMY might be a promising formula for NAFLD therapy. Herein, we verify that the LMY formula effectively reduces hepatic steatosis in diet-induced zebrafish and NAFLD model mice in a time- and dose-dependent manner. Mechanistically, LMY suppresses Yap1-mediated Foxm1 activation, which is crucial for the occurrence and development of NAFLD. Consequently, lipogenesis is ameliorated by LMY administration. In summary, the LMY formula alleviates diet-induced NAFLD in zebrafish and mice by inhibiting Yap1/Foxm1 signaling-mediated NAFLD pathology.
非酒精性脂肪性肝病（NAFLD）是最常见的慢性肝病，全球患病率为25%。NAFLD患者更容易患上晚期肝病、心血管疾病或II型糖尿病。然而，不幸的是，目前仍缺乏美国食品药品监督管理局（FDA）批准的用于治疗NAFLD的药物。连梅饮（LMY）是一种用于治疗肝脏疾病数十年的中药配方。它最近已被应用于与胰岛素抵抗密切相关的II型糖尿病。鉴于NAFLD是另一种与胰岛素抵抗有关的疾病，我们推测LMY可能是一种有前景的NAFLD治疗配方。在此，我们证实LMY配方能以时间和剂量依赖性方式有效减轻饮食诱导的斑马鱼和NAFLD模型小鼠的肝脂肪变性。机制上，LMY抑制Yap1介导的Foxm1激活，这对NAFLD的发生和发展至关重要。因此，给予LMY可改善脂肪生成。总之，LMY配方通过抑制Yap1/Foxm1信号介导的NAFLD病理过程，减轻了饮食诱导的斑马鱼和小鼠的NAFLD。
