Development of a Novel Anti-liver Fibrosis Formula with Luteolin, Licochalcone A, Aloe-emodin and Acacetin by Network Pharmacology and Transcriptomics Analysis

Overview

Journal Pharm Biol

Specialties Pharmacology
Pharmacy

Date 2021 Nov 22

PMID 34808067

Citations 7

Authors

Yuan Zhou

Rong Wu

Fei-Fei Cai

Wen-Jun Zhou

Yi-Yu Lu

Hui Zhang

Qi-Long Chen

Ming-Yu Sun

Shi-Bing Su

Affiliations

Soon will be listed here.

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 study. The anti-fibrosis effect was evaluated by and 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 CCl-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 and .

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.

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