Predicting the Mechanism of Tiannanxing-shengjiang Drug Pair in Treating Pain Using Network Pharmacology and Molecular Docking Technology


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Abstract

Objective:This study aimed to analyze the potential targets and mechanism of the Tiannanxing-shengjiang drug pair in pain treatment using network pharmacology and molecular docking technology.

Methods:The active components and target proteins of Tiannanxing-Shengjiang were obtained from the TCMSP database. The pain-related genes were acquired from the DisGeNET database. The common target genes between Tiannanxing-Shengjiang and pain were identified and subjected to the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses on the DAVID website. AutoDockTools and molecular dynamics simulation analysis were used to assess the binding of the components with the target proteins.

Results:Ten active components were screened out, such as stigmasterol, β-sitosterol, and dihydrocapsaicin. A total of 63 common targets between the drug and pain were identified. GO analysis showed the targets to be mainly associated with biological processes, such as inflammatory response and forward regulation of the EKR1 and EKR2 cascade. KEGG analysis revealed 53 enriched pathways, including pain-related calcium signaling, cholinergic synaptic signaling, and serotonergic pathway. Five compounds and 7 target proteins showed good binding affinities. These data suggest that Tiannanxing-shengjiang may alleviate pain through specific targets and signaling pathways.

Conclusion:The active ingredients in Tiannanxing-shengjiang might alleviate pain by regulating genes, such as CNR1, ESR1, MAPK3, CYP3A4, JUN, and HDAC1 through the signaling pathways, including intracellular calcium ion conduction, cholinergic prominent signaling, and cancer signaling pathway.

About the authors

Boning Wang

, Graduate School of Beijing University of Chinese Medicine

Email: info@benthamscience.net

Yanlei Wang

, Graduate School of Beijing University of Chinese Medicine

Email: info@benthamscience.net

Peng Mao

Department of Pain Medicine, The First Affiliated Hospital of Tsinghua University

Email: info@benthamscience.net

Yi Zhang

Department of Pain Medicine, The First Affiliated Hospital of Tsinghua University,

Email: info@benthamscience.net

Yifan Li

Department of Pain Medicine, The First Affiliated Hospital of Tsinghua University,

Email: info@benthamscience.net

Xing Liu

, raduate School of Beijing University of Chinese Medicine

Email: info@benthamscience.net

Bifa Fan

Department of Pain Medicine, The First Affiliated Hospital of Tsinghua University,

Author for correspondence.
Email: info@benthamscience.net

References

  1. Mao, P.; Lin, X.Q.; Li, Y.F.; Wu, Y. Chronic secondary musculoskeletal pain. Chinese J. Pain Med., 2021, 27(5), 323-326. doi: 10.3969/j.issn.1006-9852.2021.05.002
  2. Li, Y.F.; Fan, B.F.; Li, C.R.; Wang, B.N.; Li, M.Q.; Xu, Y.M.; Wu, D.S.; Fu, Z.J.; Chen, Y.Z.; Mao, P. Efficacy and safety of chuanxiong qingnao granule for the treatment of migraine: A multicenter randomized, double-blind, placebo-controlled prospective clinical trial. Chinese J. Pain Med., 2019, 25(10), 739-743,748.
  3. Scholl, L.; Seth, P.; Kariisa, M.; Wilson, N.; Baldwin, G. Drug and opioid-involved overdose deaths - United States, 2013–2017. MMWR Morb. Mortal. Wkly. Rep., 2018, 67(5152), 1419-1427. doi: 10.15585/mmwr.mm675152e1 PMID: 30605448
  4. Duan, X.C.; Huang, S.; Peng, D.Y.; Han, L.; Wang, X.L.; Wang, Y.C.; Pan, L.Y. Application of network pharmacology in the study of traditional Chinese medicine formula. Zhongguo Yaolixue Tongbao, 2020, 36(3), 303-308.
  5. Hao, D.C.; Xiao, P.G. Network pharmacology: A Rosetta Stone for traditional Chinese medicine. Drug Dev. Res., 2014, 75(5), 299-312. doi: 10.1002/ddr.21214 PMID: 25160070
  6. Chen, R.M.; Jiang, M.; Yin, S.M.; Qiu, J.C.; Bian, H.M. Impact of compound nanxing pain paste on analgesia and the expression of C-Fos in model rats with formaldehyde-induced inflammatory pain. World J. Integrat. Trad. West. Med., 2008, 3(8), 454-456.
  7. Mao, Z.J.; Zhang, C.A.; Wu, F.; Wei, P.K. Effects of aqueous extract of chinese medicine raw pinellia and nanxing on human gastric cancer cells BGC823. Xiandai Shengwu Yixue Jinzhan, 2011, (10), 1861-1880.
  8. Kang, F.; Yan, W.J.; Shi, Z.T.; Qi, F.Y.; Huang, X.J. Experimental observation of analgesic effect of ginger and exploration of its mechansim. Shaanxi Med. J., 2010, 39(8), 954-955.
  9. Zhang, W.; Chen, Y.; Jiang, H.; Yang, J.; Wang, Q.; Du, Y.; Xu, H. Integrated strategy for accurately screening biomarkers based on metabolomics coupled with network pharmacology. Talanta, 2020, 211, 120710. doi: 10.1016/j.talanta.2020.120710 PMID: 32070601
  10. Gfeller, D.; Grosdidier, A.; Wirth, M.; Daina, A.; Michielin, O.; Zoete, V. Swiss Target Prediction: A web server for target prediction of bioactive small molecules. Nucleic Acids Res., 2014, 42(Web Server issue), W32-W38. doi: 10.1093/nar/gku293
  11. UniProt Consortium. UniProt: A worldwide hub of protein knowledge. Nucleic Acids Res., 2019, 47(D1), D506-D515. doi: 10.1093/nar/gky1049 PMID: 30395287
  12. Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res., 2003, 13(11), 2498-2504. doi: 10.1101/gr.1239303 PMID: 14597658
  13. von Mering, C.; Jensen, L.J.; Snel, B.; Hooper, S.D.; Krupp, M.; Foglierini, M.; Jouffre, N.; Huynen, M.A.; Bork, P. STRING: Known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Res., 2004, 33(Database issue), D433-D437. doi: 10.1093/nar/gki005 PMID: 15608232
  14. Shen, F.; Yongrong, W.; Kuang, G.; Zhao, Y.; Xia, Y.; Deng, D. Potential molecular mechanism of Zhuifeng Tougu capsule in treating rheumatoid arthritis and osteoarthritis based on network pharmacology and molecular docking technology. World Sci. Technol.Modern. Trad. Chinese Med., 2021, 22(10), 3526-3537.
  15. Huang, D.W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc., 2009, 4(1), 44-57. doi: 10.1038/nprot.2008.211 PMID: 19131956
  16. Rajeswari, M.; Santhi, N.; Bhuvaneswari, V. Pharmacophore and virtual screening of JAK3 inhibitors. Bioinformation, 2014, 10(3), 157-163. doi: 10.6026/97320630010157 PMID: 24748756
  17. Liu, Y.B.; Pan, N.S.; Mo, Y.M. A review of the research progress of the chinese medicine tiannanxing. Sci. Technol. West China, 2015, 14(6), 106-107, 150.
  18. Nadaf, A.; Zanan, R. Economical importance of indian pandanus species. In: Indian Pandanaceae - An Overview; Springer India, 2012; pp. 127-137. doi: 10.1007/978-81-322-0753-5_7
  19. Pandith, H.; Zhang, X.; Thongpraditchote, S.; Wongkrajang, Y.; Gritsanapan, W.; Baek, S.J. Effect of Siam weed extract and its bioactive component scutellarein tetramethyl ether on anti-inflammatory activity through NF-κB pathway. J. Ethnopharmacol., 2013, 147(2), 434-441. doi: 10.1016/j.jep.2013.03.033 PMID: 23535395
  20. Walker, C.I.B.; Oliveira, S.M.; Tonello, R.; Rossato, M.F.; da Silva Brum, E.; Ferreira, J.; Trevisan, G. Anti-nociceptive effect of stigmasterol in mouse models of acute and chronic pain. Naunyn Schmiedebergs Arch. Pharmacol., 2017, 390(11), 1163-1172. doi: 10.1007/s00210-017-1416-x PMID: 28821921
  21. Mizerska-Wasiak, M.; Małdyk, J.; Rybi-Szumińska, A.; Wasilewska, A.; Miklaszewska, M.; Pietrzyk, J.; Firszt-Adamczyk, A.; Stankiewicz, R.; Bieniaś, B.; Zajączkowska, M.; Gadomska-Prokop, K.; Grenda, R.; Pukajło-Marczyk, A.; Zwolińska, D.; Szczepańska, M.; Turczyn, A.; Roszkowska-Blaim, M. Relationship between serum IgA/C3 ratio and severity of histological lesions using the Oxford classification in children with IgA nephropathy. Pediatr. Nephrol., 2015, 30(7), 1113-1120. doi: 10.1007/s00467-014-3024-z PMID: 25549975
  22. Amsalem, M.; Poilbout, C.; Ferracci, G.; Delmas, P.; Padilla, F. Membrane cholesterol depletion as a trigger of Nav1.9 channel‐mediated inflammatory pain. EMBO J., 2018, 37(8), e97349. doi: 10.15252/embj.201797349 PMID: 29459435
  23. Binzen, U.; Greffrath, W.; Hennessy, S.; Bausen, M.; Saaler-Reinhardt, S.; Treede, R.D. Co-expression of the voltage-gated potassium channel Kv1.4 with transient receptor potential channels (TRPV1 and TRPV2) and the cannabinoid receptor CB1 in rat dorsal root ganglion neurons. Neuroscience, 2006, 142(2), 527-539. doi: 10.1016/j.neuroscience.2006.06.020 PMID: 16889902
  24. Khasabova, I.A.; Khasabov, S.G.; Harding-Rose, C.; Coicou, L.G.; Seybold, B.A.; Lindberg, A.E.; Steevens, C.D.; Simone, D.A.; Seybold, V.S. A decrease in anandamide signaling contributes to the maintenance of cutaneous mechanical hyperalgesia in a model of bone cancer pain. J. Neurosci., 2008, 28(44), 11141-11152. doi: 10.1523/JNEUROSCI.2847-08.2008 PMID: 18971457
  25. Pernía-Andrade, A.J.; Kato, A.; Witschi, R.; Nyilas, R.; Katona, I.; Freund, T.F.; Watanabe, M.; Filitz, J.; Koppert, W.; Schüttler, J.; Ji, G.; Neugebauer, V.; Marsicano, G.; Lutz, B.; Vanegas, H.; Zeilhofer, H.U. Spinal endocannabinoids and CB1 receptors mediate C-fiber-induced heterosynaptic pain sensitization. Science, 2009, 325(5941), 760-764. doi: 10.1126/science.1171870 PMID: 19661434
  26. Evrard, H.C. Estrogen synthesis in the spinal dorsal horn: a new central mechanism for the hormonal regulation of pain. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2006, 291(2), R291-R299. doi: 10.1152/ajpregu.00930.2005 PMID: 16914420
  27. Dolgikh, O.V.; Zaitseva, N.V.; Nosov, A.E.; Krivtsov, A.V.; Dianova, D.G.; Kazakova, O.A.; Otavina, E.A.; Alikina, I.N. Analysis of the role of carriership of polymorphic genotypes of ESR1, eNOS, and APOE4 genes in the development of arterial hypertension in men. Bull. Exp. Biol. Med., 2018, 164(6), 753-756. doi: 10.1007/s10517-018-4073-2 PMID: 29658078
  28. Li, M.L.; Hong, Y.G. Mitogen-activated protein kinase and pain. Chinese J. Pain Med., 2010, 16(4), 241-244.
  29. Chi, L.Q.; Lu, X.; Wang, L.; Liu, S.P.; Ding, N.; Zhang, H.Y.; e, W. Detection of cytochrome P450 3A4 gene polymorphism guides for labor analgesia with sufentanil medication. Beijing Da Xue Xue Bao, 2015, 47(4), 653-656. PMID: 26284404
  30. Kharasch, E.D.; Whittington, D.; Hoffer, C. Influence of hepatic and intestinal cytochrome P4503A activity on the acute disposition and effects of oral transmucosal fentanyl citrate. Anesthesiology, 2004, 101(3), 729-737. doi: 10.1097/00000542-200409000-00022 PMID: 15329598
  31. Yan, X.T.; Xu, Y.; Cheng, X.L.; He, X.H.; Wang, Y.; Zheng, W.Z.; Zhao, Y.; Chen, H.; Wang, Y.L. SP1, MYC, CTNNB1, CREB1, JUN genes as potential therapy targets for neuropathic pain of brain. J. Cell. Physiol., 2019, 234(5), 6688-6695. doi: 10.1002/jcp.27413 PMID: 30478830
  32. Wakabayashi, H.; Wakisaka, S.; Hiraga, T.; Hata, K.; Nishimura, R.; Tominaga, M.; Yoneda, T. Decreased sensory nerve excitation and bone pain associated with mouse Lewis lung cancer in TRPV1-deficient mice. J. Bone Miner. Metab., 2018, 36(3), 274-285. doi: 10.1007/s00774-017-0842-7 PMID: 28516219

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