PI3K/AKT/mTOR通路
药理学
木犀草素
蛋白激酶B
肝纤维化
纤维化
肝星状细胞
体内
化学
阿卡汀
医学
生物
细胞凋亡
内分泌学
内科学
生物化学
抗氧化剂
槲皮素
类黄酮
生物技术
芹菜素
作者
Yuan Zhou,Rong Wu,Fei-Fei Cai,Wenjun Zhou,Yi‐Yu Lu,Hui Zhang,Qilong Chen,Mingyu Sun,Shi‐Bing Su
标识
DOI:10.1080/13880209.2021.1999275
摘要
Xiaoyaosan decoction (XYS), a classical Traditional Chinese Medicine (TCM) formula is used to treat liver fibrosis in clinics.This study explores defined compound combinations from XYS decoction to treat liver fibrosis.Network pharmacology combined with transcriptomics analysis was used to analyze the XYS decoction and liver depression and spleen deficiency syndrome liver fibrosis. From the constructed XYS-Syndrome-liver fibrosis network, the top 10 active formulas were developed by topological analysis according to network stability. The most active formula was determined by in vitro study. The anti-fibrosis effect was evaluated by in vitro and in vivo studies.According to the network XYS-Syndrome-liver fibrosis network, 8 key compounds and 255 combinations were predicted from in XYS. Luteolin, licochalcone A, aloe-emodin and acacetin formula (LLAAF) had a synergistic effect on the proliferation inhibition of hepatic stellate cells compared to individual compounds alone. The treatment of XYS and LLAAF showed a similar anti-liver fibrotic effect that reduced histopathological changes of liver fibrosis, Hyp content and levels of α-SMA and collagen I in CCl4-induced liver fibrosis in rats. Transcriptomics analysis revealed LLAAF regulated PI3K-Akt, AMPK, FoxO, Jak-STAT3, P53, cell cycle, focal adhesion, and PPAR signalling. Furthermore, LLAAF was confirmed to regulate Jak-STAT and PI3K-Akt-FoxO signalling in vitro and in vivo.This study developed a novel anti-liver formula LLAAF from XYS, and demonstrated its anti-liver fibrotic activity which may be involved in the regulation of Jak-STAT and PI3K-Akt-FoxO signalling.
科研通智能强力驱动
Strongly Powered by AbleSci AI