Network Pharmacology Combined with Molecular Docking Approach to Investigate the Mechanism of ChuShiWeiLing Decoction against Perianal Eczema


Цитировать

Полный текст

Аннотация

Background:ChuShiWeiLing Decoction (CSWLD) is a famous classical Chinese prescription for the treatment of eczema with desirable effect in clinical practice. It has gradually exerted good curative effects on perianal eczema (PE) in recent years, but its specific mechanism is not elucidated yet.

Objective:This research explores the underlying pharmacological mechanism of CSWLD in addressing PE through network pharmacology combined with molecular docking strategy.

Methods:The key chemical compounds and potential target genes of CSWLD were screened by bioinformatics. The major targets of CSWLD were discovered using network modules. Functional annotation of Gene Ontology (GO) was undertaken, as well as pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Molecular docking of core protein-ligand interactions was modeled using AutoDock software. Pymol software was used to perform a molecular dynamics simulation for the ideal core protein-ligand that was discovered by molecular docking.

Results:A total of 2,853 active compounds and 922 targets of CSWLD were collected. The target with a higher degree was identified through the PPI network, namely TNF, IL6, ALB, STAT3, EGFR, TLR4, CXCL8 and PTPRC. GO and KEGG analyses suggested that CSWLD treatment of PE mainly involves cellular activation, activation of leukocytes, and adhesion among leukocytes. The molecular docking results showed that wogonin, hederagenin and quercetin of CSWLD could bind to IL-6 and TNF, respectively.

Conclusion:Our results indicated that the bioactives, potential targets, and molecular mechanism of CSWLD against PE.

Об авторах

Ying Liu

Department of Anorectal Surgery, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine

Email: info@benthamscience.net

Min Hao

School of Pharmaceutical Sciences, Zhejiang Chinese Medical University

Email: info@benthamscience.net

Xinyue Fang

School of Pharmaceutical Sciences, Zhejiang Chinese Medical University

Email: info@benthamscience.net

Yifei Qian

Department of Chemistry, University of Wisconsin-Madison

Email: info@benthamscience.net

Yahui Wang

Department of Anorectal Surgery, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine

Email: info@benthamscience.net

Shuai Yan

Department of Anorectal Surgery, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine

Автор, ответственный за переписку.
Email: info@benthamscience.net

Список литературы

  1. Weyandt G, Breitkopf C, Werner RN, et al. German S1 guidelines for the diagnosis and treatment of perianal dermatitis (anal eczema). J Dtsch Dermatol Ges 2020; 18(6): 648-57. doi: 10.1111/ddg.14125 PMID: 32469472
  2. Dietrich CF, Hoch F. Analekzem. Ther Umsch 2021; 78(9): 509-12. doi: 10.1024/0040-5930/a001303 PMID: 34704478
  3. Schauber J, Weisenseel P, Ruzicka T. Topical treatment of perianal eczema with tacrolimus 0·1%. Br J Dermatol 2009; 161(6): 1384-6. doi: 10.1111/j.1365-2133.2009.09345.x PMID: 19575757
  4. Kränke B, Trummer M, Brabek E, Komericki P, Turek TD, Aberer W. Etiologic and causative factors in perianal dermatitis: Results of a prospective study in 126 patients. Wien Klin Wochenschr 2006; 118(3-4): 90-4. doi: 10.1007/s00508-006-0529-x PMID: 16703252
  5. Cheng YL, Wu YL, Li WL. Research progress on epidemiological investigation of anorectal diseases in China. Chin J Coloproctol 2022; 42(6): 74-6. doi: 10.3969/j.issn.1000-1174.2022.06.033
  6. Silverberg JI, Gelfand JM, Margolis DJ, et al. Symptoms and diagnosis of anxiety and depression in atopic dermatitis in U.S. adults. Br J Dermatol 2019; 181(3): 554-65. doi: 10.1111/bjd.17683 PMID: 30838645
  7. Liu H, Xiao J, Wu J. Investigation and analysis of the psychological status and quality of life of patients with chronic eczema. Chin J Dermatol Venereol 2012; 26: 332-3.
  8. Schauber J. Topical therapy of perianal eczema. Hautarzt 2010; 61(1): 33-8. doi: 10.1007/s00105-009-1812-3 PMID: 19967332
  9. Agulló-Pérez AD, Hervella-Garcés M, Oscoz-Jaime S, Azcona-Rodríguez M, Larrea-García M, Yanguas-Bayona JI. Perianal dermatitis. Dermatitis 2017; 28(4): 270-5. doi: 10.1097/DER.0000000000000274 PMID: 28338543
  10. Lenhard BH. On the clinical picture of anal eczema – diagnosis and therapy. Wien Med Wochenschr 2004; 154(3-4): 88-91. doi: 10.1007/s10354-004-0046-3 PMID: 15038582
  11. Gao W, Qiao X, Zhu J, Jin X, Wei Y. Clinical efficacy of tacrolimus ointment + 3% boric acid lotion joint Chinese Angelica decoction in chronic perianal eczema. Comput Math Methods Med 2021; 2021: 1-5. doi: 10.1155/2021/1016108 PMID: 34721653
  12. Weng M, Fang Z. Observation on treating perianal eczema of the Shire type with the Kushen Chushi plaster Clin Res. Zhong Yi Xue 2020; 12(11): 121-3. doi: 10.3969/j.issn.1674-7860.2020.11.046
  13. Han J. Observation on the efficacy of chushi weiling decoction combined with acupuncture in the treatment of eczema of immunological disorders. Guide Chin Med 2019; 17(28): 161. doi: 10.15912/j.cnki.gocm.2019.28.130
  14. Du JX, An CC, Xun JF. Study on the treatment of eczema by chushiweiling decoction. Modern J Integr Trad and West Med 2020; 29(30): 3410-2. doi: 10.3969/j.issn.1008-8849.2020.30.025
  15. Wu J, Zhao YM. Clinical effect of Dehumidification Weiling decoction combined with acupuncture on subacute eczema with dampness of immunological disorders. Inner Mongolia Trad Chin Med 2022; 41(3): 43-4. doi: 10.16040/j.cnki.cn15-1101.2022.03.040
  16. Liu M. The effect of the Chushi Weiling decoction on seborrheic dermatitis. Clin Res Trad Chin Med 2021; 13(22): 111-3. doi: 10.3969/j.issn.1674-7860.2021.22.035
  17. Cao T, Tan CC, Peng B. Clinical application of dehumidifying Weiling decoction in dermatology. J Clin Rational Drug Use 2020; 13(13): 110-3. doi: 10.15887/j.cnki.13-1389/r.2020.13.061
  18. Liu GH, Wang QL, Han XH. Clinical study on Chushi Weiling decoction combined with fire needle in the treatment of chronic eczema with immunological disorders. Int J Trad Chin Med 2022; 44(9): 1001-5. doi: 10.3760/cma.j.cn115398-20220402-00018
  19. Li JX, Jia XQ, He LY. Treatment of perianal eczema from ‘rheumatism heat stasis’. Int J Trad Chin Med 2022; 44(10): 1182-4. doi: 10.3760/cma.j.cn115398-20211013-00118
  20. Tan LL. ChuShi weiling decoction in treating 200 cases of chronic eczema. West J Trad Chin Med 2018; 31(12): 66-8.
  21. Yan S, Ye BR, Lu LJ. Clinical evaluation of modified chushi weiling decoction combined with Zhiyang decoction in the treatment of perianal eczema. Shenzhen J Integr Tradit Chin West Med 2022; 32(8): 61-4. doi: 10.16458/j.cnki.1007-0893.2022.08.018
  22. Zhang R, Zhu X, Bai H, Ning K. Network pharmacology databases for traditional Chinese medicine: Review and assessment. Front Pharmacol 2019; 10: 123. doi: 10.3389/fphar.2019.00123 PMID: 30846939
  23. Li S, Zhang B. Traditional Chinese medicine network pharmacology: Theory, methodology and application. Chin J Nat Med 2013; 11(2): 110-20. doi: 10.1016/S1875-5364(13)60037-0 PMID: 23787177
  24. Hao DC, Xiao PG. Network pharmacology: A Rosetta Stone for traditional Chinese medicine. Drug Dev Res 2014; 75(5): 299-312. doi: 10.1002/ddr.21214 PMID: 25160070
  25. 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
  26. Burley SK, Bhikadiya C, Bi C, et al. RCSB Protein Data Bank (RCSB.org): delivery of experimentally-determined PDB structures alongside one million computed structure models of proteins from artificial intelligence/machine learning. Nucleic Acids Res 2023; 51(D1): D488-508. doi: 10.1093/nar/gkac1077 PMID: 36420884
  27. Eberhardt J, Santos-Martins D, Tillack AF, Forli S. Auto-Dock Vina 1.2.0: New docking methods, expanded force field, and python bindings. J Chem Inf Model 2021; 61(8): 3891-8. doi: 10.1021/acs.jcim.1c00203 PMID: 34278794
  28. Kim S. Getting the most out of PubChem for virtual screening. Expert Opin Drug Discov 2016; 11(9): 843-55. doi: 10.1080/17460441.2016.1216967 PMID: 27454129
  29. Li X, Tian Y, Wu H, Wang T. Network pharmacology and molecular docking to unveil the mechanism of Shudihuang against amyotrophic lateral sclerosis. Curr Pharm Des 2023; 29(19): 1535-45. doi: 10.2174/1381612829666230621105552 PMID: 37345246
  30. O’Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. Open Babel: An open chemical toolbox. J Cheminform 2011; 3(1): 33. doi: 10.1186/1758-2946-3-33 PMID: 21982300
  31. Kalliolias GD, Ivashkiv LB. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat Rev Rheumatol 2016; 12(1): 49-62. doi: 10.1038/nrrheum.2015.169 PMID: 26656660
  32. Lee A, Qiao Y, Grigoriev G, et al. Tumor necrosis factor α induces sustained signaling and a prolonged and unremitting inflammatory response in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 2013; 65(4): 928-38. doi: 10.1002/art.37853 PMID: 23335080
  33. Feldmann M. Translating molecular insights in autoimmunity into effective therapy. Annu Rev Immunol 2009; 27(1): 1-27. doi: 10.1146/annurev-immunol-082708-100732 PMID: 19007330
  34. McEver RP. Selectins: initiators of leucocyte adhesion and signalling at the vascular wall. Cardiovasc Res 2015; 107(3): 331-9. doi: 10.1093/cvr/cvv154 PMID: 25994174
  35. Bui TM, Wiesolek HL, Sumagin R. ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis. J Leukoc Biol 2020; 108(3): 787-99. doi: 10.1002/JLB.2MR0220-549R PMID: 32182390
  36. Shi H, Wan G, Wang T, et al. Prevalence and influencing risk factors of eczema among preschool children in Urumqi city: a cross-sectional survey. BMC Pediatr 2021; 21(1): 347. doi: 10.1186/s12887-021-02819-5 PMID: 34399722
  37. Belloni B, Andres C, Ollert M, Ring J, Mempel M. Novel immunological approaches in the treatment of atopic eczema. Curr Opin Allergy Clin Immunol 2008; 8(5): 423-7. doi: 10.1097/ACI.0b013e32830fb8fd PMID: 18769195
  38. Zhang M, Zhou J, Wang L, et al. Caffeic acid reduces cutaneous tumor necrosis factor alpha (TNF-α), IL-6 and IL-1β levels and ameliorates skin edema in acute and chronic model of cutaneous inflammation in mice. Biol Pharm Bull 2014; 37(3): 347-54. doi: 10.1248/bpb.b13-00459 PMID: 24583856
  39. Cohen JN, Bowman S, Laszik ZG, North JP. Clinicopathologic overlap of psoriasis, eczema, and psoriasiform dermatoses: A retrospective study of T helper type 2 and 17 subsets, interleukin 36, and β-defensin 2 in spongiotic psoriasiform dermatitis, sebopsoriasis, and tumor necrosis factor α inhibitor–associated dermatitis. J Am Acad Dermatol 2020; 82(2): 430-9. doi: 10.1016/j.jaad.2019.08.023 PMID: 31859047
  40. Li P, Chen J, Zhang W, Fu B, Wang W. Transcriptome inference and systems approaches to polypharmacology and drug discovery in herbal medicine. J Ethnopharmacol 2017; 195: 127-36. doi: 10.1016/j.jep.2016.10.020 PMID: 27894972
  41. Lin Y, Chen XJ, He L, et al. Systematic elucidation of the bioactive alkaloids and potential mechanism from Sophora flavescens for the treatment of eczema via network pharmacology. J Ethnopharmacol 2023; 301115799. doi: 10.1016/j.jep.2022.115799 PMID: 36216196
  42. Lucas CD, Dorward DA, Sharma S, et al. Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation. Am J Respir Crit Care Med 2015; 191(6): 626-36. doi: 10.1164/rccm.201408-1565OC PMID: 25629436
  43. Sohail M, Khan FA, Shami HB, Bashir MM. Management of eczema herpeticum in a burn unit. J Pak Med Assoc 2016; 66(11): 1357-61. PMID: 27812048
  44. Imbernón-Moya A, Ortiz-de Frutos FJ, Delgado-Márquez AM. Initial assessment of patients with contact eczema. Dermosyphiliographic minutes 2016; 107: 791-3. doi: 10.1016/j.adengl.2016.08.007
  45. Peluso I, Raguzzini A, Serafini M. Effect of flavonoids on circulating levels of TNF-α and IL-6 in humans: A systematic review and meta-analysis. Mol Nutr Food Res 2013; 57(5): 784-801. doi: 10.1002/mnfr.201200721 PMID: 23471810
  46. Nguyen LTH, Oh TW, Nguyen UT, Choi MJ, Yang IJ, Shin HM. A natural compound mixture containing arctigenin, hederagenin, and baicalein alleviates atopic dermatitis in mice by regulating hpa axis and immune activity. Evid Based Complement Alternat Med 2020; 2020: 1-13. doi: 10.1155/2020/1970349 PMID: 32714398
  47. Lee JH, Lim JY, Jo EH, et al. Chijabyukpi-tang inhibits pro-inflammatory cytokines and chemokines via the Nrf2/HO-1 signaling pathway in TNF-α/IFN-γ-Stimulated HaCaT cells and ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in mice. Front Pharmacol 2020; 11: 1018. doi: 10.3389/fphar.2020.01018 PMID: 32733250
  48. Zimmermann M, Koreck A, Meyer N, et al. TNF-like weak inducer of apoptosis (TWEAK) and TNF-α cooperate in the induction of keratinocyte apoptosis. J Allergy Clin Immunol 2011; 127(1): 200. -207. e10, 207.e1-207.e10. doi: 10.1016/j.jaci.2010.11.005 PMID: 21211655
  49. Nakamura M, Lee K, Singh R, et al. Eczema as an adverse effect of anti-TNFα therapy in psoriasis and other Th1-mediated diseases: A review. J Dermatolog Treat 2017; 28(3): 237-41. doi: 10.1080/09546634.2016.1230173 PMID: 27571340
  50. Deubelbeiss C, Kolios AGA, Anzengruber F, et al. TNFα and IL‐17A are differentially expressed in psoriasis‐like vs eczema‐like drug reactions to TNFα antagonists. J Cutan Pathol 2018; 45(1): 23-8. doi: 10.1111/cup.13055 PMID: 29023827
  51. Zhu Y, Xian X, Wang Z, et al. Research progress on the relationship between atherosclerosis and inflammation. Biomolecules 2018; 8(3): 80. doi: 10.3390/biom8030080 PMID: 30142970
  52. Xun Z, Lin J, Yu Q, et al. Taurocholic acid inhibits the response to interferon-α therapy in patients with HBeAg-positive chronic hepatitis B by impairing CD8+ T and NK cell function. Cell Mol Immunol 2021; 18(2): 461-71. doi: 10.1038/s41423-020-00601-8 PMID: 33432062
  53. Wang S, Wang Y, Han B, et al. Huanglian ointment alleviates eczema by maintaining the balance of c-Jun and JunB and inhibiting AGE-RAGE-mediated proinflammation signaling pathway. Phytomedicine 2022; 105154372. doi: 10.1016/j.phymed.2022.154372 PMID: 35932609
  54. Csiszar A, Ungvari Z. Endothelial dysfunction and vascular inflammation in Type 2 diabetes: Interaction of AGE/RAGE and TNF-α signaling. Am J Physiol Heart Circ Physiol 2008; 295(2): H475-6. doi: 10.1152/ajpheart.00644.2008 PMID: 18599592
  55. 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; 144105389. doi: 10.1016/j.compbiomed.2022.105389 PMID: 35303581
  56. Wang W, Li M, Si H, Jiang Z. Network pharmacology and integrated molecular docking study on the mechanism of the therapeutic effect of fangfeng decoction in osteoarthritis. Curr Pharm Des 2023; 29(5): 379-92. doi: 10.2174/1381612829666230216095659 PMID: 36803762

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML
Скачать

© Bentham Science Publishers, 2024