Abstract
BackgroundAstragali Radix (AR) is widely-used for improving liver fibrosis, but, the mechanism of action has not been systematically explained. This study aims to investigate the mechanism of AR intervention in liver fibrosis based on comprehensive metabolomics combined with network pharmacology approach.Materials and methodsUPLC–Q-TOF/MS based metabolomics technique was used to explore the specific metabolites and possible pathways of AR affecting the pathological process of liver fibrosis. Network pharmacology analysis was introduced to explore the key targets of AR regarding the mechanisms on liver fibrosis.ResultsAR significantly reduced the levels of ALT, AST and AKP in serum, and improved pathological characteristics. Metabolomics analysis showed that the therapeutic effect of AR was mainly related to the regulation of nine metabolites, including sphingosine, 6-keto-prostaglandin F1a, LysoPC (O-18:0), 3-dehydrosphinganine, 5,6-epoxy-8,11,14-eicosatrienoic acid, leukotriene C4, taurochenodesoxycholic acid, LysoPC (18:1 (9Z)) and 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine. Pathway analysis indicated that the treatment of AR on liver fibrosis was related to arachidonic acid metabolism, ether lipid metabolism, sphingolipid metabolism, glycerophospholipid metabolism and primary bile acid biosynthesis. Validation of the key targets by network pharmacology analysis of potential metabolic markers showed that AR significantly down-regulated the expression of CYP1B1 and up-regulated the expression of CYP1A2 and PCYT1A.ConclusionMetabolomics combined with network pharmacology was used for the first time to clarify that the treatment of AR on liver fibrosis, which is related to the regulation of arachidonic acid metabolism and ether lipid metabolism by modulating the expression of CYP1A2, CYP1B1 and PCYT1A. And the integrated approach can provide new strategies and ideas for the study of molecular mechanisms of traditional Chinese medicines in the treatment of liver fibrosis.
Highlights
Astragali Radix (AR) is widely-used for improving liver fibrosis, but, the mechanism of action has not been systematically explained
Pathway analysis indicated that the treatment of AR on liver fibrosis was related to arachidonic acid metabolism, ether lipid metabolism, sphingolipid metabolism, glycerophospholipid metabolism and primary bile acid biosynthesis
In this study, UPLC–Q-TOF/MS-method based rat serum metabolomics combined with network pharmacology was firstly used to clarify the protective effect of AR on liver fibrosis, which provided an indepth understanding of the mechanism of AR on liver fibrosis
Summary
Astragali Radix (AR) is widely-used for improving liver fibrosis, but, the mechanism of action has not been systematically explained. As a worldwide clinical problem, liver fibrosis is a wound healing process with recurrent chronic liver damage [1]. It can accelerate the development of chronic liver disease by destroying normal liver parenchyma, eventually leading to cirrhosis, liver failure and even primary liver cancer [2]. The pathogenesis of liver fibrosis, such as inflammatory response, hepatic stellate cell activation and extracellular matrix formation, has been widely recognized, it has not got an effective and powerful treatment [3, 4]. In traditional Chinese formula, AR is often used for the treatment of liver fibrosis [6, 7]. AR exhibits significant advantages for the treatment of liver fibrosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
