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

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.

• 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
• Journal: Pharmaceutical biology (Pharm Biol) Vol. 59 Issue 1 Pg. 1594-1606 (Dec 2021) ISSN: 1744-5116 [Electronic] England
• PMID: 34808067 (Publication Type: Journal Article)

Chemical References

• Anthraquinones
• Chalcones
• Drugs, Chinese Herbal
• Flavones
• xiaoyaosan
• aloe emodin
• licochalcone A
• Luteolin
• acacetin

Topics

• Animals
• Anthraquinones (administration & dosage, pharmacology)
• Cell Line
• Chalcones (administration & dosage, pharmacology)
• Drug Synergism
• Drugs, Chinese Herbal (administration & dosage, chemistry, pharmacology)
• Flavones (administration & dosage, pharmacology)
• Hepatic Stellate Cells (drug effects, pathology)
• Humans
• Liver Cirrhosis (drug therapy)
• Luteolin (administration & dosage, pharmacology)
• Male
• Network Pharmacology
• Rats
• Rats, Wistar
• Signal Transduction (drug effects)
• Transcriptome