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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Autores principales: Yuan Zhou, Rong Wu, Fei-fei Cai, Wen-Jun Zhou, Yi-Yu Lu, Hui Zhang, Qi-Long Chen, Ming-Yu Sun, Shi-Bing Su
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Publicado: Taylor & Francis Group 2021
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic xiaoyaosan decoction
llaaf
anti-liver fibrotic effect
Therapeutics. Pharmacology
RM1-950
spellingShingle 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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