Xu Tian, Chen Jiahui, Shao Qi, Ji Jing, Wang Qingguo, Ma Chongyang, Wang Xueqian, Cheng Fafeng
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Heliyon. 2024 Jul 20;10(14):e34718. doi: 10.1016/j.heliyon.2024.e34718. eCollection 2024 Jul 30.
The Coptidis Rhizoma and Bovis Calculus herb pair possesses clearing heat and detoxifying effects. The aim of this study was to reveal the effects and mechanisms of the herb pair in the treatment of NASH by network pharmacology and experimental verification. A network pharmacology-based approach was employed to predict the putative mechanism of the herb pair against NASH. The high-fat diet (HFD) and methionine/choline deficient (MCD) diet induced NASH models were used to evaluate efficacy and mechanism of the herb pair. Network pharmacological analysis showed that the herb pair modulated NOD-like receptor pathway. In the HFD mice, herb pair reduced body weight, blood sugar, serum ALT, AST, TBA, TC, TG and LDL-C contents, also improved the general morphology and pathological manifestations. Hepatic transcriptomics study showed that herb pair attenuated NASH by regulating NOD-like receptor signaling pathway. Western blotting showed that herb pair reduced the protein expression levels of NLRP3, cleaved Caspase-1 and cleaved IL-1β. In the MCD mice, herb pair also reduced serum ALT, ALT and TBA levels, improved liver pathological manifestations, inhibited the protein expression levels of NLRP3, cleaved Caspase-1 and cleaved IL-1β. Our findings proved that the Coptidis Rhizoma and Bovis Calculus herb pair attenuates NASH through suppression of NLRP3 inflammasome activation. This will demonstrate effective pharmacological evidence for the clinical application of herb pair.
黄连与牛黄药对具有清热泻火解毒之功效。本研究旨在通过网络药理学和实验验证揭示该药对治疗非酒精性脂肪性肝炎（NASH）的作用及机制。采用基于网络药理学的方法预测该药对治疗NASH的潜在机制。利用高脂饮食（HFD）和蛋氨酸/胆碱缺乏（MCD）饮食诱导的NASH模型来评估该药对的疗效和机制。网络药理学分析表明，该药对可调节NOD样受体途径。在HFD小鼠中，该药对降低了体重、血糖、血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆汁酸（TBA）、总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白胆固醇（LDL-C）含量，还改善了大体形态和病理表现。肝脏转录组学研究表明，该药对通过调节NOD样受体信号通路减轻NASH。蛋白质免疫印迹法显示，该药对降低了NLRP3、裂解的半胱天冬酶-1和裂解的白细胞介素-1β的蛋白表达水平。在MCD小鼠中，该药对也降低了血清ALT、AST和TBA水平，改善了肝脏病理表现，抑制了NLRP3、裂解的半胱天冬酶-1和裂解的白细胞介素-1β的蛋白表达水平。我们的研究结果证明，黄连与牛黄药对通过抑制NLRP3炎性小体激活减轻NASH。这将为该药对的临床应用提供有效的药理学证据。
