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

Ying      Liu; Min      Hao; Xinyue      Fang; Yifei      Qian; Yahui      Wang; Shuai      Yan

doi:10.2174/0113816128298780240329075340

Abstract

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.

« Previous

[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.
 [http://dx.doi.org/10.1111/ddg.14125] [PMID: 32469472]

[2]
Dietrich CF, Hoch F. Analekzem. Ther Umsch  2021; 78(9): 509-12.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/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.
 [http://dx.doi.org/10.2174/1381612829666230216095659] [PMID: 36803762]

Rights & Permissions Print Cite

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/0113816128298780240329075340	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286

Current Pharmaceutical Design

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

Abstract Play Pause

Related Journals

Related Books

Abstract