Network Pharmacology and In vitro Experimental Verification to Explore the Mechanism of Chaiqin Qingning Capsule in the Treatment of Pain


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Abstract

Background:Chaiqin Qingning capsule (CQQNC) has been used to relieve pain in practice. However, the active components, pain targets, and molecular mechanisms for pain control are unclear.

Objective:To explore the active components and potential mechanisms of the analgesic effect of CQQNC through network pharmacology and in vitro experiments.

Methods:The main active components and the corresponding targets of CQQNC were screened from the TCMSP and the SwissTargetPrediction databases. Pain-related targets were selected in the OMIM, Gene- Cards, and DrugBank databases. These targets were intersected to obtain potential analgesic targets. The analgesic targets were imported into the STRING and DAVID databases for protein-protein interaction (PPI), gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Cytoscape software (V3.7.1) was used to construct an active component-intersection network. Finally, the key components were docked with the core targets. The analgesic mechanism of CQQNC was verified by RAW264.7 cell experiment.

Results:30 active CQQNC components, 617 corresponding targets, and 3,214 pain-related target genes were found. The main active components were quercetin, kaempferol, and chenodeoxycholic acid etc. The key targets were ALB, AKT1, TNF, IL6, TP53, IL1B, and SRC. CQQNC can exert an analgesic effect through PI3K-Akt, MAPK signaling pathways, etc. Molecular docking showed that these active components had good binding activities with key targets. The results of in vitro experiments showed that CQQNC could exert antiinflammatory and analgesic effects through MAPK/AKT/NF-kB signaling pathways.

Conclusion:CQQNC exerts pain control through inhibiting MAPK/AKT/NF-kB signaling pathways.

About the authors

Hongjin Gao

Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University

Email: info@benthamscience.net

Zhengwei Chen

Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University

Email: info@benthamscience.net

Buliduhong Halihaman

Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University

Email: info@benthamscience.net

Lianzhan Huang

Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University

Email: info@benthamscience.net

Zhen Wang

Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University

Email: info@benthamscience.net

Xuansheng Ding

Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University

Author for correspondence.
Email: info@benthamscience.net

References

  1. Jain N, Lodha R, Kabra SK. Upper respiratory tract infections. Indian J Pediatr 2001; 68(12): 1135-8. doi: 10.1007/BF02722930 PMID: 11838568
  2. Esposito C, Garzarella EU, Bocchino B, et al. A standardized polyphenol mixture extracted from poplar-type propolis for remission of symptoms of uncomplicated upper respiratory tract infection (URTI): A monocentric, randomized, double-blind, placebo-controlled clinical trial. Phytomedicine 2021; 80: 153368. doi: 10.1016/j.phymed.2020.153368 PMID: 33091857
  3. Gomes FIF, Cunha FQ, Cunha TM. Peripheral nitric oxide signaling directly blocks inflammatory pain. Biochem Pharmacol 2020; 176: 113862. doi: 10.1016/j.bcp.2020.113862 PMID: 32081790
  4. Zhao J, Hao Y, Xia X, et al. Chaiqin qingning capsule inhibits influenza virus infection and inflammation in vitro and in vivo. Evid Based Complement Alternat Med 2021; 2021: 1-9. doi: 10.1155/2021/6640731 PMID: 34552653
  5. Zhang L, Wu B, Li XY, et al. Simultaneous determination of ten constituents in chaiqin qingning capsule by high-performance liquid chromatography coupled with triple-quadrupole mass spectrometry. Pharmacogn Mag 2017; 13(52): 566-70. doi: 10.4103/pm.pm_81_17 PMID: 29200714
  6. Zhao CL, Pan Z, Li J, Ling CL. Clinical study on chaiqin qingning capsule combined with ribavirin in the treatment of acute upper respiratory tract infection. Moder Med Clini 2021; 36(03): 475-8.
  7. Xie W, Lei Y. Clinical study on Chaiqin Qingning capsule in the treatment of lung Wei syndrome caused by wind febrile disease in children with upper respiratory tract infection. Chin Moder Doct 2020; 58(21): 85-8.
  8. Wei JL, Huang XM, Liu YF, Jiang L. Clinical observation of Chaiqin Qingning capsule in the treatment of lung Wei syndrome of wind febrile disease with acute upper respiratory tract infection. Chinese J Emerg Med 2017; 26(08): 1446-8.
  9. Yuan C, Wang MH, Wang F, et al. Network pharmacology and molecular docking reveal the mechanism of Scopoletin against non-small cell lung cancer. Life Sci 2021; 270: 119105. doi: 10.1016/j.lfs.2021.119105 PMID: 33497736
  10. Pinzi L, Rastelli G. Molecular docking: Shifting paradigms in drug discovery. Int J Mol Sci 2019; 20(18): 4331. doi: 10.3390/ijms20184331 PMID: 31487867
  11. Ferreira L, dos Santos R, Oliva G, Andricopulo A. Molecular docking and structure-based drug design strategies. Molecules 2015; 20(7): 13384-421. doi: 10.3390/molecules200713384 PMID: 26205061
  12. Lin Y, Shen C, Wang F, Fang Z, Shen G. Network pharmacology and molecular docking study on the potential mechanism of Yi-Qi-Huo-xue-tong-luo formula in treating diabetic peripheral neuropathy. J Diabetes Res 2021; 2021: 1-16. doi: 10.1155/2021/9941791 PMID: 34159207
  13. Li X, Wei S, Niu S, et al. Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of Huanglian Jiedu Decoction against sepsis. Comput Biol Med 2022; 144: 105389. doi: 10.1016/j.compbiomed.2022.105389 PMID: 35303581
  14. Liu Y, Yu L, Zhang J, Xie D, Zhang X, Yu J. Network pharmacology-based and molecular docking-based analysis of suanzaoren decoction for the treatment of Parkinson’s disease with sleep disorder. BioMed Res Int 2021; 2021: 1-12. doi: 10.1155/2021/1752570 PMID: 34660782
  15. Xu L, Zhang J, Wang Y, Zhang Z, Wang F, Tang X. Uncovering the mechanism of Ge-Gen-Qin-Lian decoction for treating ulcerative colitis based on network pharmacology and molecular docking verification. Biosci Rep 2021; 41(2): BSR20203565. doi: 10.1042/BSR20203565 PMID: 33409535
  16. Ru J, Li P, Wang J, et al. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J Cheminform 2014; 6(1): 13. doi: 10.1186/1758-2946-6-13 PMID: 24735618
  17. Xu Y, Yu Y, Wang Q, et al. Active components of Bupleurum chinense and Angelica biserrata showed analgesic effects in formalin induced pain by acting on Nav1.7. J Ethnopharmacol 2021; 269: 113736. doi: 10.1016/j.jep.2020.113736 PMID: 33359917
  18. Daina A, Michielin O, Zoete V. SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Res 2019; 47(W1): W357-64. doi: 10.1093/nar/gkz382 PMID: 31106366
  19. Otasek D, Morris JH, Bouças J, Pico AR, Demchak B. Cytoscape automation: Empowering workflow-based network analysis. Genome Biol 2019; 20(1): 185. doi: 10.1186/s13059-019-1758-4 PMID: 31477170
  20. Wang J, Peng W, Wu FX. Computational approaches to predicting essential proteins: A survey. Proteomics Clin Appl 2013; 7(1-2): 181-92. doi: 10.1002/prca.201200068 PMID: 23165920
  21. Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010; 31(2): 455-61. doi: 10.1002/jcc.21334 PMID: 19499576
  22. Liu J, Liu J, Tong X, et al. Network pharmacology prediction and molecular docking-based strategy to discover the potential pharmacological mechanism of huai hua san against ulcerative colitis. Drug Des Devel Ther 2021; 15: 3255-76. doi: 10.2147/DDDT.S319786 PMID: 34349502
  23. Que W, Wu Z, Chen M, et al. Molecular mechanism of Gelsemium elegans (gardner and Champ.) benth. Front Pharmacol 2022; 12: 792932. doi: 10.3389/fphar.2021.792932 PMID: 35046814
  24. Rittner HL, Machelska H, Stein C. Leukocytes in the regulation of pain and analgesia. J Leukoc Biol 2005; 78(6): 1215-22. doi: 10.1189/jlb.0405223 PMID: 16204636
  25. Koo HJ, Yoon WJ, Sohn EH, et al. The analgesic and anti-inflammatory effects of Litsea japonica fruit are mediated via suppression of NF-κB and JNK/p38 MAPK activation. Int Immunopharmacol 2014; 22(1): 84-97. doi: 10.1016/j.intimp.2014.06.007 PMID: 24968348
  26. Valério DA, Georgetti SR, Magro DA, et al. Quercetin reduces inflammatory pain: Inhibition of oxidative stress and cytokine production. J Nat Prod 2009; 72(11): 1975-9. doi: 10.1021/np900259y PMID: 19899776
  27. Ye G, Lin C, Zhang Y, et al. Quercetin alleviates neuropathic pain in the rat CCI model by mediating AMPK/MAPK pathway. J Pain Res 2021; 14: 1289-301. doi: 10.2147/JPR.S298727 PMID: 34040433
  28. Chang S, Li X, Zheng Y, et al. Kaempferol exerts a neuroprotective effect to reduce neuropathic pain through TLR4/NF‐ĸB signaling pathway. Phytother Res 2022; 36(4): 1678-91. doi: 10.1002/ptr.7396 PMID: 35234314
  29. Santos Passos FR, Pereira EWM, Heimfarth L, et al. Role of peripheral and central sensitization in the anti-hyperalgesic effect of hecogenin acetate, an acetylated sapogenin, complexed with β-cyclodextrin: Involvement of NFκB and p38 MAPK pathways. Neuropharmacology 2021; 186: 108395. doi: 10.1016/j.neuropharm.2020.108395 PMID: 33516738
  30. Carballo-Villalobos AI, González-Trujano ME, Pellicer F, Alvarado-Vásquez N, López-Muñoz FJ. Central and peripheral anti-hyperalgesic effects of diosmin in a neuropathic pain model in rats. Biomed Pharmacother 2018; 97: 310-20. doi: 10.1016/j.biopha.2017.10.077 PMID: 29091880
  31. Yao Y, Chang B, Li S. Relationship of inflammation with trigeminal neuralgia. J Craniofac Surg 2020; 31(2): e110-3. doi: 10.1097/SCS.0000000000005879 PMID: 31609955
  32. Wang L, Lin J, Li W. Pharmacological mechanism of danggui-sini formula for intervertebral disc degeneration: A network pharmacology study. BioMed Res Int 2021; 2021: 1-12. doi: 10.1155/2021/5165075 PMID: 34805401
  33. Zhang C, Wan H, Ma K, Luan S, Li H. Identification of biomarkers related to neuropathic pain induced by peripheral nerve injury. J Mol Neurosci 2019; 69(4): 505-15. doi: 10.1007/s12031-019-01322-y PMID: 31352588
  34. Hers I, Vincent EE, Tavaré JM. Akt signalling in health and disease. Cell Signal 2011; 23(10): 1515-27. doi: 10.1016/j.cellsig.2011.05.004 PMID: 21620960
  35. Nicholson KM, Anderson NG. The protein kinase B/Akt signalling pathway in human malignancy. Cell Signal 2002; 14(5): 381-95. doi: 10.1016/S0898-6568(01)00271-6 PMID: 11882383
  36. Pan HT, Xi ZQ, Wei XQ, Wang K. A network pharmacology approach to predict potential targets and mechanisms of "Ramulus Cinnamomi (cassiae) - Paeonia lactiflora" herb pair in the treatment of chronic pain with comorbid anxiety and depression. Ann Med 2022; 54(1): 413-25. doi: 10.1080/07853890.2022.2031268 PMID: 35098831
  37. Li D, Chen H, Luo XH, Sun Y, Xia W, Xiong YC. CX3CR1-mediated Akt1 activation contributes to the paclitaxel-induced painful peripheral neuropathy in rats. Neurochem Res 2016; 41(6): 1305-14. doi: 10.1007/s11064-016-1827-y PMID: 26961886
  38. Ge MM, Zhou YQ, Tian XB, et al. Src-family protein tyrosine kinases: A promising target for treating chronic pain. Biomed Pharmacother 2020; 125: 110017. doi: 10.1016/j.biopha.2020.110017 PMID: 32106384
  39. Ma H, Yao C, Ma P, et al. Src activation in the hypothalamic arcuate nucleus may play an important role in pain hypersensitivity. Sci Rep 2019; 9(1): 3827. doi: 10.1038/s41598-019-40572-z PMID: 30846840
  40. Cui CY, Liu X, Peng MH, Liu Q, Zhang Y. Identification of key candidate genes and biological pathways in neuropathic pain. Comput Biol Med 2022; 150: 106135. doi: 10.1016/j.compbiomed.2022.106135 PMID: 36166989
  41. Lee HS, Lee IH, Kang K, Park SI, Kwon TW, Lee DY. An investigation of the molecular mechanisms underlying the analgesic effect of jakyak-gamcho decoction: A network pharmacology study. Evid Based Complement Alternat Med 2020; 2020: 1-20. doi: 10.1155/2020/6628641 PMID: 33343676
  42. Chen P, Lin D, Wang C, et al. Proteomic analysis of emodin treatment in neuropathic pain reveals dysfunction of the calcium signaling pathway. J Pain Res 2021; 14: 613-22. doi: 10.2147/JPR.S290681 PMID: 33707969
  43. Liu W, Lv Y, Ren F. PI3K/Akt pathway is required for spinal central sensitization in neuropathic pain. Cell Mol Neurobiol 2018; 38(3): 747-55. doi: 10.1007/s10571-017-0541-x PMID: 28849293
  44. Li M, Li Z, Ma X, et al. Huangqi guizhi wuwu decoction can prevent and treat oxaliplatin-induced neuropathic pain by TNFα/IL-1β/IL-6/MAPK/NF-kB pathway. Aging 2022; 14(12): 5013-22. doi: 10.18632/aging.203794 PMID: 35759577
  45. Sandireddy R, Yerra VG, Areti A, Komirishetty P, Kumar A. Neuroinflammation and oxidative stress in diabetic neuropathy: Futuristic strategies based on these targets. Int J Endocrinol 2014; 2014: 1-10. doi: 10.1155/2014/674987 PMID: 24883061
  46. Gong G, Guan YY, Zhang ZL, et al. Isorhamnetin: A review of pharmacological effects. Biomed Pharmacother 2020; 128: 110301. doi: 10.1016/j.biopha.2020.110301 PMID: 32502837
  47. Chi G, Zhong W, Liu Y, et al. Isorhamnetin protects mice from lipopolysaccharide-induced acute lung injury via the inhibition of inflammatory responses. Inflamm Res 2016; 65(1): 33-41. doi: 10.1007/s00011-015-0887-9 PMID: 26525359
  48. Qi F, Sun J, Yan J, Li C, Lv X. Anti-inflammatory effects of isorhamnetin on LPS-stimulated human gingival fibroblasts by activating Nrf2 signaling pathway. Microb Pathog 2018; 120: 37-41. doi: 10.1016/j.micpath.2018.04.049 PMID: 29704670
  49. Bakrim S, Benkhaira N, Bourais I, et al. Health benefits and pharmacological properties of stigmasterol. Antioxidants 2022; 11(10): 1912. doi: 10.3390/antiox11101912 PMID: 36290632
  50. Si W, Li X, Jing B, et al. Stigmasterol regulates microglial M1/M2 polarization via the TLR4/NF‐κB pathway to alleviate neuropathic pain. Phytother Res 2023; ptr.8039. doi: 10.1002/ptr.8039

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