Guo Jia, Shi Anhua, Sun Yanhong, Zhang Shunzhen, Feng Xiaoyi, Chen Yifan, Yao Zheng
School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650500, People's Republic of China.
Dongtai Hospital of Traditional Chinese Medicine, Dongtai, Jiangsu, 224200, People's Republic of China.
Diabetes Metab Syndr Obes. 2025 Apr 17;18:1165-1194. doi: 10.2147/DMSO.S507039. eCollection 2025.
In this study, we investigated the effect of Shenling Baizhu San(SLBZS), Quzhi Ruangan Fang(QZRGF) and Gexia Zhuyu Tang(GXZYT) on the intestinal flora of NAFLD rats through network pharmacology and experimental validation.
Protein-protein interaction, Gene Ontology (GO), and molecular docking were performed. Male Sprague-Dawley (SD) rats were divided into 6 groups: Normal, Model, SLBZS (7.2g/kg), QZRGF (27.72g/kg), GXZYT (28.8 g/kg) and positive control (Fenofibrate, 18mg/kg); the NAFLD model was established by High-fat diet. After one week of acclimatisation feeding consecutively, continuous gavage was given for 8 W and 12 W. Serum, liver and faeces were collected and biochemical and pathological indices were determined. The diversity and abundance of intestinal flora were also analyzed using 16S rDNA amplified sequencing.
A total of 132 active ingredients were obtained from the screening results of SLBZS. A total of 202 active ingredients were obtained from the screening results of GXZYT. The screening results of QZRGF obtained 34 active ingredients. Nine common hub genes were screened from the PPI network. GO functional analysis reported that these targets were mainly closely related to the response to bacterial molecules. The molecular docking results indicated that the 11 core constituents in three compound prescriptions has good binding ability with MAPK1, AKT1, CASP3, FOS, TP53, STAT3, MAPK3.
The Chinese herbal compounds SLBZS, QZRGF and GXZYT may exert lipid-lowering effects through multi-components, multi-targets and multi-methods for the treatment of NAFLD while improving the diversity and abundance of the intestinal flora of the rats, and the best effect was achieved with SLBZS.
本研究通过网络药理学和实验验证,探讨参苓白术散(SLBZS)、祛脂软肝方(QZRGF)和膈下逐瘀汤(GXZYT)对非酒精性脂肪性肝病(NAFLD)大鼠肠道菌群的影响。
进行蛋白质-蛋白质相互作用、基因本体论(GO)和分子对接。将雄性Sprague-Dawley(SD)大鼠分为6组:正常组、模型组、参苓白术散组(7.2g/kg)、祛脂软肝方组(27.72g/kg)、膈下逐瘀汤组(28.8g/kg)和阳性对照组(非诺贝特,18mg/kg);采用高脂饮食建立NAFLD模型。连续适应性喂养1周后,连续灌胃8周和12周。收集血清、肝脏和粪便,测定生化和病理指标。同时采用16S rDNA扩增测序分析肠道菌群的多样性和丰度。
参苓白术散筛选结果共获得132种活性成分。膈下逐瘀汤筛选结果共获得202种活性成分。祛脂软肝方筛选结果获得34种活性成分。从蛋白质-蛋白质相互作用(PPI)网络中筛选出9个共同的枢纽基因。GO功能分析表明,这些靶点主要与对细菌分子的反应密切相关。分子对接结果表明,三个复方中的11种核心成分与丝裂原活化蛋白激酶1(MAPK1)、蛋白激酶B(AKT1)、半胱天冬酶3(CASP3)、原癌基因c-fos(FOS)、肿瘤蛋白p53(TP53)、信号转导和转录激活因子3(STAT3)、丝裂原活化蛋白激酶3(MAPK3)具有良好的结合能力。
中药复方参苓白术散、祛脂软肝方和膈下逐瘀汤可能通过多成分、多靶点、多途径发挥降脂作用,从而治疗NAFLD,同时改善大鼠肠道菌群的多样性和丰度,其中参苓白术散效果最佳。