Development of a novel anti-liver fibrosis formula with luteolin, licochalcone A, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis
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 tran...
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2021
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oai:doaj.org-article:de0df60900da41b4879357df7764c9d82021-11-26T11:19:47ZDevelopment of a novel anti-liver fibrosis formula with luteolin, licochalcone A, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis1388-02091744-511610.1080/13880209.2021.1999275https://doaj.org/article/de0df60900da41b4879357df7764c9d82021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2021.1999275https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context 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.Yuan ZhouRong WuFei-fei CaiWen-Jun ZhouYi-Yu LuHui ZhangQi-Long ChenMing-Yu SunShi-Bing SuTaylor & Francis Grouparticlexiaoyaosan decoctionllaafanti-liver fibrotic effectTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 59, Iss 1, Pp 1594-1606 (2021) |
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xiaoyaosan decoction llaaf anti-liver fibrotic effect Therapeutics. Pharmacology RM1-950 |
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xiaoyaosan decoction llaaf anti-liver fibrotic effect Therapeutics. Pharmacology RM1-950 Yuan Zhou Rong Wu Fei-fei Cai Wen-Jun Zhou Yi-Yu Lu Hui Zhang Qi-Long Chen Ming-Yu Sun Shi-Bing Su Development of a novel anti-liver fibrosis formula with luteolin, licochalcone A, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis |
description |
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. |
format |
article |
author |
Yuan Zhou Rong Wu Fei-fei Cai Wen-Jun Zhou Yi-Yu Lu Hui Zhang Qi-Long Chen Ming-Yu Sun Shi-Bing Su |
author_facet |
Yuan Zhou Rong Wu Fei-fei Cai Wen-Jun Zhou Yi-Yu Lu Hui Zhang Qi-Long Chen Ming-Yu Sun Shi-Bing Su |
author_sort |
Yuan Zhou |
title |
Development of a novel anti-liver fibrosis formula with luteolin, licochalcone A, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis |
title_short |
Development of a novel anti-liver fibrosis formula with luteolin, licochalcone A, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis |
title_full |
Development of a novel anti-liver fibrosis formula with luteolin, licochalcone A, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis |
title_fullStr |
Development of a novel anti-liver fibrosis formula with luteolin, licochalcone A, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis |
title_full_unstemmed |
Development of a novel anti-liver fibrosis formula with luteolin, licochalcone A, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis |
title_sort |
development of a novel anti-liver fibrosis formula with luteolin, licochalcone a, aloe-emodin and acacetin by network pharmacology and transcriptomics analysis |
publisher |
Taylor & Francis Group |
publishDate |
2021 |
url |
https://doaj.org/article/de0df60900da41b4879357df7764c9d8 |
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