Development of a novel anti-liver fibrosis formula with luteolin, licochalcone A, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis. (1st January 2021)

• Record Type: Journal Article
• Authors: Zhou, Yuan; Wu, Rong; Cai, Fei-fei; Zhou, Wen-Jun; Lu, Yi-Yu; Zhang, Hui; Chen, Qi-Long; Sun, Ming-Yu; Su, Shi-Bing
• Is Part Of: Pharmaceutical biology. Volume 59:Number 1(2021)
• Page Start: 1592
• Page End: 1604
• Publication Date: 2021-01-01
• Subjects: Xiaoyaosan decoction -- LLAAF -- anti-liver fibrotic effect; Pharmacognosy -- Periodicals; Materia medica, Vegetable -- Periodicals; 615.321
• DOI: 10.1080/13880209.2021.1999275
• Languages: English
• ISSNs: 1388-0209

Abstract

Abstract: Context: Xiaoyaosan decoction (XYS), a classical Traditional Chinese Medicine (TCM) formula is used to treat liver fibrosis in clinics. Objective: This study explores defined compound combinations from XYS decoction to treat liver fibrosis. Materials and methods: 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. Results: 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 . Conclusions: 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.