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Systematic understanding of the potential targets and pharmacological mechanisms of acteoside by network pharmacology approach

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Abstract

Acteoside (ACT) is one of the most major components isolated from Cistanches Herba, a traditional Chinese medicine. However, its extensive pharmacological effects and multitarget features cause lacking of a systematic overview of its molecular mechanisms. In this study, we aimed to predict the potential targets and pharmacological mechanisms of ACT via network pharmacology strategy and provide scientific evidence of drug discovery. The druglikeness of ACT was measured using the TCMSP database, and its potential targets were identified by both of ChemMapper and PharmMapper based on 3D-structure similarity. By mapping the potential targets obtained from ChemMapper and PharmMapper, the intersecting targets were screened as candidate targets. GO classification, pathway enrichment analysis, and drug–target–pathway networks were constructed to give a visual view. In addition, experimental validations were carried out using HepG2 cell lines. Results showed that ACT has good druggability, and 13 protein targets were predicted. Network pharmacology analysis reflected that these potential targets were mainly associated with cancer, metabolism, antioxidant effects, and other physiological processes. Furthermore, the results of experimental validation indicated that ACT has no toxicity and has protective effects in hepatic lipid metabolism. Generally, ACT is predicted to multitargets and multipathways to form a network that exerts systematic pharmacological effects.

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References

  • Baumgartner M, Weiss A, Fritzius T, Heinrich J, Moelling K (2009) The PDZ protein MPP2 interacts with c-Src in epithelial cells. Exp Cell Res 315:2888–2898

    Article  CAS  Google Scholar 

  • Boezio B, Audouze K, Ducrot P, Taboureau O (2017) Network-based approaches in pharmacology. Mol Inform 36. https://doi.org/10.1002/minf.201700048

    Article  Google Scholar 

  • Bowman T, Broome MA, Sinibaldi D, Wharton W, Pledger WJ, Sedivy JM, Irby R, Yeatman T, Courtneidge SA, Jove R (2001) Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis. Proc Natl Acad Sci USA 98:7319–7324

    Article  CAS  Google Scholar 

  • Browning JD, Horton JD (2004) Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114:147–152

    Article  CAS  Google Scholar 

  • Chen F, Eckman EA, Eckman CB (2006) Reductions in levels of the Alzheimer’s amyloid beta peptide after oral administration of ginsenosides. FASEB J 20:1269–1271

    Article  CAS  Google Scholar 

  • Day CP (2002) Non-alcoholic steatohepatitis (NASH): where are we now and where are we going? Gut 50:585–588

    Article  CAS  Google Scholar 

  • Esposito E, Dal Toso R, Pressi G, Bramanti P, Meli R, Cuzzocrea S (2010) Protective effect of verbascoside in activated C6 glioma cells: possible molecular mechanisms. Naunyn Schmiedebergs Arch Pharm 381:93–105

    Article  CAS  Google Scholar 

  • Gan L, Li X, Zhu M, Chen C, Luo H, Zhou Q (2018) Acteoside relieves mesangial cell injury by regulating Th22 cell chemotaxis and proliferation in IgA nephropathy. Ren Fail 40:364–370

    Article  CAS  Google Scholar 

  • Gao L, Wang XD, Niu YY, Duan DD, Yang X, Hao J, Zhu CH, Chen D, Wang KX, Qin XM, Wu XZ (2016) Molecular targets of Chinese herbs: a clinical study of hepatoma based on network pharmacology. Sci Rep. 6:24944

    Article  CAS  Google Scholar 

  • Hobbs GA, Der CJ, Rossman KL (2016) RAS isoforms and mutations in cancer at a glance. J Cell Sci 129:1287–1292

    Article  CAS  Google Scholar 

  • Huan SK, Wang KT, Lee CJ, Sung CH, Chien TY, Wang CC (2012) Wu-Chia-Pi solution attenuates carbon tetrachloride-induced hepatic injury through the antioxidative abilities of its components acteoside and quercetin. Molecules 17:14673–14684

    Article  CAS  Google Scholar 

  • Ji SL, Cao KK, Zhao XX, Kang NX, Zhang Y, Xu QM, Yang SL, Liu YL, Wang C (2019) Antioxidant activity of phenylethanoid glycosides on glutamate-induced neurotoxicity. Biosci Biotechnol Biochem 83:2016–2026

    Article  CAS  Google Scholar 

  • Jia WQ, Wang ZT, Zou MM, Lin JH, Li YH, Zhang L, Xu RX (2018) Verbascoside inhibits glioblastoma cell proliferation, migration and invasion while promoting apoptosis through upregulation of protein tyrosine phosphatase SHP-1 and inhibition of STAT3 phosphorylation. Cell Physiol Biochem 47:1871–1882

    Article  CAS  Google Scholar 

  • Jiang Y, Tu PF (2009) Analysis of chemical constituents in Cistanche species. J Chromatogr A 1216:1970–1979

    Article  CAS  Google Scholar 

  • Jing W, Chunhua M, Shumin W (2015) Effects of acteoside on lipopolysaccharide-induced inflammation in acute lung injury via regulation of NF-kappaB pathway in vivo and in vitro. Toxicol Appl Pharm 285:128–135

    Article  CAS  Google Scholar 

  • Johnson DS, Chen YH (2012) Ras family of small GTPases in immunity and inflammation. Curr Opin Pharm 12:458–463

    Article  CAS  Google Scholar 

  • Khullar M, Sharma A, Wani A, Sharma N, Sharma N, Chandan BK, Kumar A, Ahmed Z (2019) Acteoside ameliorates inflammatory responses through NFkB pathway in alcohol induced hepatic damage. Int Immunopharmacol 69:109–117

    Article  CAS  Google Scholar 

  • Koo KA, Sung SH, Park JH, Kim SH, Lee KY, Kim YC (2005) In vitro neuroprotective activities of phenylethanoid glycosides from Callicarpa dichotoma. Planta Med 71:778–780

    Article  CAS  Google Scholar 

  • Lapillo M, Tuccinardi T, Martinelli A, Macchia M, Giordano A, Poli G (2019) Extensive reliability evaluation of docking-based target-fishing strategies. Int J Mol Sci 20. https://doi.org/10.3390/ijms20051023

    Article  CAS  Google Scholar 

  • Li M, Zhou F, Xu T, Song H, Lu B (2018) Acteoside protects against 6-OHDA-induced dopaminergic neuron damage via Nrf2-ARE signaling pathway. Food Chem Toxicol 119:6–13

    Article  CAS  Google Scholar 

  • Li S, Zhang B (2013) Traditional Chinese medicine network pharmacology: theory, methodology and application. Chin J Nat Med 11:110–120

    Article  Google Scholar 

  • Mun H, Jeon TJ (2012) Regulation of actin cytoskeleton by Rap1 binding to RacGEF1. Mol Cells 34:71–76

    Article  CAS  Google Scholar 

  • Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–335

    Article  CAS  Google Scholar 

  • Peerzada KJ, Faridi AH, Sharma L, Bhardwaj SC, Satti NK, Shashi B, Tasduq SA (2016) Acteoside-mediates chemoprevention of experimental liver carcinogenesis through STAT-3 regulated oxidative stress and apoptosis. Environ Toxicol 31:782–798

    Article  CAS  Google Scholar 

  • Ru J, Li P, Wang J, Zhou W, Li B, Huang C, Li P, Guo Z, Tao W, Yang Y, Xu X, Li Y, Wang Y, Yang L (2014) TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform 6:13

    Article  Google Scholar 

  • Shen B (2015) A new golden age of natural products drug discovery. Cell 163:1297–1300

    Article  CAS  Google Scholar 

  • Shiao YJ, Su MH, Lin HC, Wu CR (2017) Acteoside and isoacteoside protect amyloid beta peptide induced cytotoxicity, cognitive deficit and neurochemical disturbances in vitro and in vivo. Int J Mol Sci 18. https://doi.org/10.3390/ijms18040895

    Article  Google Scholar 

  • Su G, Morris JH, Demchak B, Bader GD (2014) Biological network exploration with Cytoscape 3. Curr Protoc Bioinform 47:8.13.1–8.13.24

    Article  Google Scholar 

  • Taniyama Y, Weber DS, Rocic P, Hilenski L, Akers ML, Park J, Hemmings BA, Alexander RW, Griendling KK (2003) Pyk2- and Src-dependent tyrosine phosphorylation of PDK1 regulates focal adhesions. Mol Cell Biol 23:8019–8029

    Article  CAS  Google Scholar 

  • Tian S, Wang J, Li Y, Li D, Xu L, Hou T (2015) The application of in silico drug-likeness predictions in pharmaceutical research. Adv Drug Deliv Rev 86:2–10

    Article  CAS  Google Scholar 

  • Wang HQ, Xu YX, Zhu CQ (2012) Upregulation of heme oxygenase-1 by acteoside through ERK and PI3K/Akt pathway confer neuroprotection against beta-amyloid-induced neurotoxicity. Neurotox Res 21:368–378

    Article  Google Scholar 

  • Wang J, Gao L, Lee YM, Kalesh KA, Ong YS, Lim J, Jee JE, Sun H, Lee SS, Hua ZC, Lin Q (2016) Target identification of natural and traditional medicines with quantitative chemical proteomics approaches. Pharm Ther 162:10–22

    Article  CAS  Google Scholar 

  • Wang X, Shen Y, Wang S, Li S, Zhang W, Liu X, Lai L, Pei J, Li H (2017) PharmMapper 2017 update: a web server for potential drug target identification with a comprehensive target pharmacophore database. Nucleic Acids Res 45:W356–W360

    Article  CAS  Google Scholar 

  • Wang Y, Cao H, Chen J, Mcniven MA (2011) A direct interaction between the large GTPase dynamin-2 and FAK regulates focal adhesion dynamics in response to active Src. Mol Biol Cell 22:1529–1538

    Article  CAS  Google Scholar 

  • Wu CJ, Chien MY, Lin NH, Lin YC, Chen WY, Chen CH, Tzen JTC (2019) Echinacoside isolated from cistanche tubulosa putatively stimulates growth hormone secretion via activation of the ghrelin receptor. Molecules 24. https://doi.org/10.3390/molecules24040720

    Article  CAS  Google Scholar 

  • Yang L, Zhang B, Liu J, Dong Y, Li Y, Li N, Zhao X, Snooks H, Hu C, Ma X (2019) Protective effect of acteoside on ovariectomy-induced bone loss in mice. Int J Mol Sci 20. https://doi.org/10.3390/ijms20122974

    Article  CAS  Google Scholar 

  • Yazici D, Sezer H (2017) Insulin resistance, obesity and lipotoxicity. Adv Exp Med Biol 960:277–304

    Article  CAS  Google Scholar 

  • Yu G, Wang LG, Han Y, He QY (2012) clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16:284–287

    Article  CAS  Google Scholar 

Download references

Funding

This research was supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region, China (Grant No. 2017D01C213).

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Correspondence to Na Mi.

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Aisa, Y., Yunusi, K., Chen, Q. et al. Systematic understanding of the potential targets and pharmacological mechanisms of acteoside by network pharmacology approach. Med Chem Res 29, 793–801 (2020). https://doi.org/10.1007/s00044-020-02524-5

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  • DOI: https://doi.org/10.1007/s00044-020-02524-5

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