Predicting the Mechanism of Tiannanxing-shengjiang Drug Pair in Treating Pain Using Network Pharmacology and Molecular Docking Technology
- Authors: Wang B.1, Wang Y.1, Mao P.2, Zhang Y.3, Li Y.3, Liu X.4, Fan B.3
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Affiliations:
- , Graduate School of Beijing University of Chinese Medicine
- Department of Pain Medicine, The First Affiliated Hospital of Tsinghua University
- Department of Pain Medicine, The First Affiliated Hospital of Tsinghua University,
- , raduate School of Beijing University of Chinese Medicine
- Issue: Vol 20, No 5 (2024)
- Pages: 463-473
- Section: Chemistry
- URL: https://rjeid.com/1573-4099/article/view/644095
- DOI: https://doi.org/10.2174/1573409919666230525122447
- ID: 644095
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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
- 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
- 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.
- Scholl, L.; Seth, P.; Kariisa, M.; Wilson, N.; Baldwin, G. Drug and opioid-involved overdose deaths - United States, 20132017. MMWR Morb. Mortal. Wkly. Rep., 2018, 67(5152), 1419-1427. doi: 10.15585/mmwr.mm675152e1 PMID: 30605448
- 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.
- 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
- 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.
- 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.
- 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.
- 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
- 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
- UniProt Consortium. UniProt: A worldwide hub of protein knowledge. Nucleic Acids Res., 2019, 47(D1), D506-D515. doi: 10.1093/nar/gky1049 PMID: 30395287
- 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
- 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
- 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.
- 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
- 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
- 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.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Li, M.L.; Hong, Y.G. Mitogen-activated protein kinase and pain. Chinese J. Pain Med., 2010, 16(4), 241-244.
- 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
- 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
- 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
- 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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