Journal of Southern Medical University ›› 2021, Vol. 41 ›› Issue (8): 1131-1141.doi: 10.12122/j.issn.1673-4254.2021.08.02

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Therapeutic mechanism of the Mongolian medicine Qiwei Qinggan Powder against liver fibrosis based on UHPLC-TOF-MS combined with network pharmacological methods

ZHANG Chunyan, YAN Yuxin, GAO Xiaoyang, MA Yuehong   

  1. Department of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot 010059, China
  • Online:2021-08-20 Published:2021-09-07

Abstract: Objective To elucidate the chemical composition of the Mongolian medicine Qiwei Qinggan Powder and explore its key targets, related pathways and its therapeutic mechanism for liver fibrosis. Methods UHPLC-TOF-MS was used to analyze the composition of Qiwei Qinggan Powder. The therapeutic targets of Qiwei Qinggan Powder were screened in Swiss Target Prediction database, and liver fibrosis-related targets were screened in TTD and GeneCards databases to identify the anti-fibrosis targets of Qiwei Qinggan Powder by intersection using Venny.2.1.0. The protein interaction was analyzed using STRING database, the GO functions and KEGG pathways were analyzed on the Metascape platform, and the core targets and active components were verified by molecular docking using AutoDock software. The therapeutic mechanism of Qiwei Qinggan Powder against liver fibrosis was verified in rat models and cell experiment. Results We identified a total of 45 chemical constituents in Qiwei Qinggan Powder, including flavonoids, alkaloids, coumarins, terpenes, phenols and fatty acids. Network pharmacological analysis identified 62 targets of Qiwei Qinggan Powder, including 10 core targets. GO enrichment analysis suggested that the therapeutic effect of Qiwei Qinggan Powder was mediated by biological processes (BP), cell components (CC) and molecular functions (MF). KEGG enrichment results showed that PI3K/Akt, Rap1, MAPK, AMPK and PPAR were all pathways associated with liver fibrosis. Molecular docking showed that quercetin, luteolin and kaempferol could bind to Akt1, PIK3R1 and MAPK1, respectively. In rat models of liver fibrosis, treatment with Qiwei Qinggan Powder significantly suppressed proliferation of fibrous tissues and inflammatory cell infiltration to improve fibrosis in the liver tissue. Western blotting demonstrated that Qiwei Qinggan Powder significantly decreased the expressions of the Liver fibrosis markers including α-SMA, Collagen1, PI3K and Akt (P<0.01). In vitro cell experiment, Qiwei Qinggan Powder-containing serum obviously promoted apoptosis of HSC-T6 cells. Conclusion The therapeutic effect of Qiwei Qinggan Powder against liver fibrosis is mediated by multiple components, targets and channels, and its mechanism may involve the regulation of PI3K, Akt and other key targets and modulation of cell apoptosis and energy metabolism.

Key words: Mongolian medicine; Qiwei Qinggan Powder; liver fibrosis; UHPLC-TOF-MS; network pharmacology; PI3K/Akt