Xu Ruohui, Wu Jiaxuan, Pan Jiashu, Zhang Shengan, Yang Yunuo, Zhang Li, Zhou Wenjun, Wu Na, Hu Dan, Ji Guang, Dang Yanqi
Institute of Digestive Diseases, China-Canada Center of Research for Digestive Diseases (ccCRDD), Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Traditional Chinese Medicine, School of Medicine, First Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
Front Pharmacol. 2024 Aug 23;15:1444561. doi: 10.3389/fphar.2024.1444561. eCollection 2024.
(GJLZ) decoction is a classical traditional Chinese medicine prescription. Through invigorating , activating and dissipating , GJLZ decoction is widely applied for the treatment of chronic digestive disease, including nonalcoholic fatty liver disease. However, efficacy and mechanism of GJLZ decoction behind nonalcoholic steatohepatitis (NASH) treatment remains unelucidated. NASH was induced in mice, followed by treatment with GJLZ decoction. Various methods including hematoxylin-eosin, oil red O staining, and triglyceride analysis were employed to evaluate the treatment effects of GJLZ decoction on NASH. Gut microbiota, metabolomics, cell viability assays, immunofluorescence and Western blotting were performed to unveil the mechanism behind GJLZ decoction. GJLZ decoction treatment significantly improved hepatic steatosis in mice with NASH. It led to remodeling of gut flora and metabolite structures, including the 12-tridecenoic acid level. 12-Tridecenoic acid aggravated hepatic steatosis by promoting acetyl-coenzyme A carboxylase alpha (ACC) expression and inhibiting carnitine palmitoyltransferase 1A (CPT1A) expression. GJLZ decoction treatment reduced the 12-tridecenoic acid level, inhibited ACC activity and promoted CPT1A expression. Our results demonstrated that 12-tridecenoic acid aggravated hepatic steatosis by affecting the ACC-CPT1A axis and GJLZ decoction treatment effectively reduced the 12-tridecenoic acid level and improved steatosis.
（加减六君子汤）汤剂是一种经典的中药方剂。通过健脾、行气和化痰，加减六君子汤被广泛应用于治疗慢性消化系统疾病，包括非酒精性脂肪性肝病。然而，加减六君子汤治疗非酒精性脂肪性肝炎（NASH）背后的疗效和机制仍未阐明。在小鼠中诱导出NASH，然后用加减六君子汤进行治疗。采用苏木精-伊红染色、油红O染色和甘油三酯分析等多种方法来评估加减六君子汤对NASH的治疗效果。进行了肠道微生物群、代谢组学、细胞活力测定、免疫荧光和蛋白质免疫印迹分析，以揭示加减六君子汤背后的作用机制。加减六君子汤治疗显著改善了NASH小鼠的肝脂肪变性。它导致肠道菌群和代谢物结构的重塑，包括12-十三碳烯酸水平。12-十三碳烯酸通过促进乙酰辅酶A羧化酶α（ACC）的表达和抑制肉碱棕榈酰转移酶1A（CPT1A）的表达来加重肝脂肪变性。加减六君子汤治疗降低了12-十三碳烯酸水平，抑制了ACC活性并促进了CPT1A的表达。我们的结果表明，12-十三碳烯酸通过影响ACC-CPT1A轴加重肝脂肪变性，而加减六君子汤治疗有效地降低了12-十三碳烯酸水平并改善了脂肪变性。
