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Chinese Medicine
Published in: Chinese Medicine 1/2019

Open Access 01-12-2019 | Research

Metabolomics combined with network pharmacology exploration reveals the modulatory properties of Astragali Radix extract in the treatment of liver fibrosis

Authors: Dan Wang, Ruisheng Li, Shizhang Wei, Sijia Gao, Zhuo Xu, Honghong Liu, Ruilin Wang, Haotian Li, Huadan Cai, Jian Wang, Yanling Zhao

Published in: Chinese Medicine | Issue 1/2019

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Abstract

Background

Astragali 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 methods

UPLC–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.

Results

AR 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.

Conclusion

Metabolomics 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.
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Literature
1.
2.
3.
Schuppan D, Ashfaq-Khan M, Yang AT, Kim YO. Liver fibrosis: direct antifibrotic agents and targeted therapies. Matrix Biol. 2018;68–69:435–51.CrossRefPubMed
4.
Yoon YJ, Friedman SL, Lee YA. Antifibrotic therapies: where are we now? Semin Liver Dis. 2016;36(1):87–98.CrossRefPubMed
5.
Li AP, Li ZY, Sun HF, Li K, Qin XM, Du GH. Comparison of two different Astragali Radix by a (1)H NMR-based metabolomic approach. J Proteome Res. 2015;14(5):2005–16.CrossRefPubMed
6.
Liu L, Leng J, Yang X, Liao L, Cen Y, Xiao A, et al. Rapid screening and identification of BSA bound ligands from radix astragali using BSA immobilized magnetic nanoparticles coupled with HPLC-MS. Molecules. 2016;21(11):1471.CrossRefPubMedCentral
7.
Gong AGW, Duan R, Wang HY, Kong XP, Dong TTX, Tsim KWK, et al. Evaluation of the pharmaceutical properties and value of Astragali Radix. Medicines. 2018;5(2):46.CrossRefPubMedCentral
8.
Zhou Y, Tong X, Ren S, Wang X, Chen J, Mu Y, et al. Synergistic anti-liver fibrosis actions of total astragalus saponins and glycyrrhizic acid via TGF-beta1/Smads signaling pathway modulation. J Ethnopharmacol. 2016;190:83–90.CrossRefPubMed
9.
Huang W, Li L, Tian X, Yan J, Yang X, Wang X, et al. Astragalus and Paeoniae radix rubra extract inhibits liver fibrosis by modulating the transforming growth factorbeta/Smad pathway in rats. Mol Med Rep. 2015;11(2):805–14.CrossRefPubMed
10.
Simeonova R, Bratkov VM, Kondeva-Burdina M, Vitcheva V, Manov V, Krasteva I. Experimental liver protection of n-butanolic extract of Astragalus monspessulanus L. on carbon tetrachloride model of toxicity in rat. Redox Rep. 2015;20(4):145–53.CrossRefPubMed
11.
Vitcheva V, Simeonova R, Krasteva I, Nikolov S, Mitcheva M. Protective effects of a purified saponin mixture from Astragalus corniculatus Bieb., in vivo hepatotoxicity models. Phytother Res. 2013;27(5):731–6.CrossRefPubMed
12.
Allam RM, Selim DA, Ghoneim AI, Radwan MM, Nofal SM, Khalifa AE, et al. Hepatoprotective effects of Astragalus kahiricus root extract against ethanol-induced liver apoptosis in rats. Chin J Nat Med. 2013;11(4):354–61.PubMed
13.
Lee JS, Cho JH, Lee DS, Son CG. genotoxicity evaluation of an ethanol extract mixture of Astragali Radix and salviae miltiorrhizae radix. Evid Based Complement Alternat Med. 2018;2018:5684805.PubMedPubMedCentral
14.
Yu SY, Ouyang HT, Yang JY, Huang XL, Yang T, Duan JP, et al. Subchronic toxicity studies of Radix Astragali extract in rats and dogs. J Ethnopharmacol. 2007;110(2):352–5.CrossRefPubMed
15.
Wang X, Zhang A, Sun H. Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma. Hepatology. 2013;57(5):2072–7.CrossRefPubMed
16.
Zhang Y, Zhang M, Li H, Zhao H, Wang F, He Q, et al. Serum metabonomics study of the hepatoprotective effect of amarogentin on CCl4-induced liver fibrosis in mice by GC-TOF-MS analysis. J Pharm Biomed Anal. 2018;149:120–7.CrossRefPubMed
17.
18.
Yan Y, Du C, Li Z, Zhang M, Li J, Jia J, et al. Comparing the antidiabetic effects and chemical profiles of raw and fermented Chinese Ge-Gen-Qin-Lian decoction by integrating untargeted metabolomics and targeted analysis. Chin Med. 2018;13:54.CrossRefPubMedPubMedCentral
19.
Zhang Y, Li W, Zou L, Gong Y, Zhang P, Xing S, et al. Metabonomic study of the protective effect of Fukeqianjin formula on multi-pathogen induced pelvic inflammatory disease in rats. Chin Med. 2018;13:61.CrossRefPubMedPubMedCentral
20.
Li A-P, Li Z-Y, Qu T-L, Qin X-M, Du G-H. Nuclear magnetic resonance based metabolomic differentiation of different Astragali Radix. Chin J Nat Med. 2017;15(5):363–74.PubMed
21.
Lyu M, Zhou Z, Wang X, Lv H, Wang M, Pan G, et al. Network pharmacology-guided development of a novel integrative regimen to prevent acute graft-vs.-host disease. Front Pharmacol. 2018;9:1440.CrossRefPubMedPubMedCentral
22.
Zhu B, Zhang W, Lu Y, Hu S, Gao R, Sun Z, et al. Network pharmacology-based identification of protective mechanism of Panax notoginseng saponins on aspirin induced gastrointestinal injury. Biomed Pharmacother. 2018;105:159–66.CrossRefPubMed
23.
24.
Wei S, Qian L, Niu M, Liu H, Yang Y, Wang Y, et al. The modulatory properties of Li-Ru-Kang treatment on hyperplasia of mammary glands using an integrated approach. Front Pharmacol. 2018;9:651.CrossRefPubMedPubMedCentral
25.
Worley B, Powers R. PCA as a practical indicator of OPLS-DA model reliability. Curr Metab. 2016;4(2):97–103.CrossRef
26.
Worley B, Powers R. Multivariate analysis in metabolomics. Curr Metab. 2013;1(1):92–107.
27.
Blasco H, Blaszczynski J, Billaut JC, Nadal-Desbarats L, Pradat PF, Devos D, et al. Comparative analysis of targeted metabolomics: dominance-based rough set approach versus orthogonal partial least square-discriminant analysis. J Biomed Inform. 2015;53:291–9.CrossRefPubMed
28.
Creydt M, Fischer M. Plant metabolomics: maximizing metabolome coverage by optimizing mobile phase additives for nontargeted mass spectrometry in positive and negative electrospray ionization mode. Anal Chem. 2017;89(19):10474–86.CrossRefPubMed
29.
Wang X, Zhang C, Zheng M, Gao F, Zhang J, Liu F. Metabolomics analysis of l-arginine induced gastrointestinal motility disorder in rats using UPLC-MS after magnolol treatment. Front Pharmacol. 2019;10:183.CrossRefPubMedPubMedCentral
30.
Kim DJ, Chung H, Ji SC, Lee S, Yu KS, Jang IJ, et al. Ursodeoxycholic acid exerts hepatoprotective effects by regulating amino acid, flavonoid, and fatty acid metabolic pathways. Metabolomics. 2019;15(3):30.CrossRefPubMed
31.
Yu J, He JQ, Chen DY, Pan QL, Yang JF, Cao HC, et al. Dynamic changes of key metabolites during liver fibrosis in rats. World J Gastroenterol. 2019;25(8):941–54.CrossRefPubMedPubMedCentral
32.
Jiang W, Si L, Li P, Bai B, Qu J, Hou B, et al. Serum metabonomics study on antidiabetic effects of fenugreek flavonoids in streptozotocin-induced rats. J Chromatogr B. 2018;1092:466–72.CrossRef
33.
Gai Z, Visentin M, Gui T, Zhao L, Thasler WE, Hausler S, et al. Effects of farnesoid X receptor activation on arachidonic acid metabolism, NF-kB signaling, and hepatic inflammation. Mol Pharmacol. 2018;94(2):802–11.CrossRefPubMed
34.
Dean JM, Lodhi IJ. Structural and functional roles of ether lipids. Protein Cell. 2018;9(2):196–206.CrossRefPubMed
35.
Barr J, Caballeria J, Martinez-Arranz I, Dominguez-Diez A, Alonso C, Muntane J, et al. Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression. J Proteome Res. 2012;11(4):2521–32.CrossRefPubMedPubMedCentral
36.
Jang JE, Park HS, Yoo HJ, Baek IJ, Yoon JE, Ko MS, et al. Protective role of endogenous plasmalogens against hepatic steatosis and steatohepatitis in mice. Hepatology. 2017;66(2):416–31.CrossRefPubMedPubMedCentral
37.
38.
Zhou C, Jia HM, Liu YT, Yu M, Chang X, Ba YM, et al. Metabolism of glycerophospholipid, bile acid and retinol is correlated with the early outcomes of autoimmune hepatitis. Mol BioSyst. 2016;12(5):1574–85.CrossRefPubMed
39.
Fader KA, Nault R, Zhang C, Kumagai K, Harkema JR, Zacharewski TR. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited effects on bile acid homeostasis: alterations in biosynthesis, enterohepatic circulation, and microbial metabolism. Sci Rep. 2017;7(1):5921.CrossRefPubMedPubMedCentral
40.
Zhou J, Wen Q, Li SF, Zhang YF, Gao N, Tian X, et al. Significant change of cytochrome P450s activities in patients with hepatocellular carcinoma. Oncotarget. 2016;7(31):50612–23.PubMedPubMedCentral
41.
Wuensch T, Heucke N, Wizenty J, Quint J, Sinn B, Arsenic R, et al. Hepatic CYP1A2 activity in liver tumors and the implications for preoperative volume-function analysis. Am J Physiol Gastrointest Liver Physiol. 2019;316(5):G608–14.CrossRefPubMed
42.
Larsen MC, Bushkofsky JR, Gorman T, Adhami V, Mukhtar H, Wang S, et al. Cytochrome P450 1B1: an unexpected modulator of liver fatty acid homeostasis. Arch Biochem Biophys. 2015;571:21–39.CrossRefPubMedPubMedCentral
43.
44.
Payne F, Lim K, Girousse A, Brown RJ, Kory N, Robbins A, et al. Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease. Proc Natl Acad Sci USA. 2014;111(24):8901–6.CrossRefPubMed
45.
Yen CL, Cheong ML, Grueter C, Zhou P, Moriwaki J, Wong JS, et al. Deficiency of the intestinal enzyme acyl CoA:monoacylglycerol acyltransferase-2 protects mice from metabolic disorders induced by high-fat feeding. Nat Med. 2009;15(4):442–6.CrossRefPubMedPubMedCentral
46.
Devasthale P, Cheng D. Monoacylglycerol acyltransferase 2 (MGAT2) inhibitors for the treatment of metabolic diseases and nonalcoholic steatohepatitis (NASH). J Med Chem. 2018;61(22):9879–88.CrossRefPubMed
47.
Fan J, Chen Q, Wei L, Zhou X, Wang R, Zhang H. Asiatic acid ameliorates CCl4-induced liver fibrosis in rats: involvement of Nrf2/ARE, NF-kappaB/IkappaBalpha, and JAK1/STAT3 signaling pathways. Drug Des Devel Ther. 2018;12:3595–605.CrossRefPubMedPubMedCentral
48.
Wei L, Chen Q, Guo A, Fan J, Wang R, Zhang H. Asiatic acid attenuates CCl4-induced liver fibrosis in rats by regulating the PI3K/AKT/mTOR and Bcl-2/Bax signaling pathways. Int Immunopharmacol. 2018;60:1–8.CrossRefPubMed
49.
He S, Yang Y, Liu X, Huang W, Zhang X, Yang S, et al. Compound Astragalus and Salvia miltiorrhiza extract inhibits cell proliferation, invasion and collagen synthesis in keloid fibroblasts by mediating transforming growth factor-beta/Smad pathway. Br J Dermatol. 2012;166(3):564–74.CrossRefPubMed
50.
Wang R, Wang J, Song F, Li S, Yuan Y. Tanshinol ameliorates CCl4-induced liver fibrosis in rats through the regulation of Nrf2/HO-1 and NF-kappaB/IkappaBalpha signaling pathway. Drug Des Dev Ther. 2018;12:1281–92.CrossRef
Metadata
Title
Metabolomics combined with network pharmacology exploration reveals the modulatory properties of Astragali Radix extract in the treatment of liver fibrosis
Authors
Dan Wang
Ruisheng Li
Shizhang Wei
Sijia Gao
Zhuo Xu
Honghong Liu
Ruilin Wang
Haotian Li
Huadan Cai
Jian Wang
Yanling Zhao
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Chinese Medicine / Issue 1/2019
Electronic ISSN: 1749-8546
DOI
https://doi.org/10.1186/s13020-019-0251-z

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