Skip to content
2000
image of Elucidating the Mechanism of Xiaoqinglong Decoction in Chronic Urticaria Treatment: An Integrated Approach of Network Pharmacology, Bioinformatics Analysis, Molecular Docking, and Molecular Dynamics Simulations

Abstract

Introduction

Xiaoqinglong Decoction (XQLD) is a traditional Chinese medicinal formula commonly used to treat chronic urticaria (CU). However, its underlying therapeutic mechanisms remain incompletely characterized. This study employed an integrated approach combining network pharmacology, bioinformatics, molecular docking, and molecular dynamics simulations to identify the active components, potential targets, and related signaling pathways involved in XQLD's therapeutic action against CU, thereby providing a mechanistic foundation for its clinical application.

Methods

The active components of XQLD and their corresponding targets were identified using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. CU-related targets were retrieved from the OMIM and GeneCards databases. Subsequently, core components and targets were determined via protein-protein interaction (PPI) network analysis and component-target-pathway network construction. Topological analyses were performed using Cytoscape software to prioritize core nodes within these networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database to identify enriched biological processes and signaling pathways. Molecular docking was performed to evaluate binding interactions between key components and core targets, while molecular dynamics (MD) simulations were employed to assess the stability of the component-target complexes with the lowest binding energy. Finally, CU-related targets of XQLD were validated using datasets from the Gene Expression Omnibus (GEO) database.

Results

A total of 135 active components and 249 potential targets of XQLD were identified, alongside 1,711 CU-related targets. Core components, such as quercetin, kaempferol, beta-sitosterol, naringenin, stigmasterol, and luteolin, exhibited high degree values in the constructed networks. The core targets identified included AKT1, TNF, IL6, TP53, PTGS2, CASP3, BCL2, ESR1, PPARG, and MAPK3. GO and KEGG pathway enrichment analyses revealed the PI3K-Akt signaling pathway as a central regulatory mechanism. Molecular docking studies demonstrated strong binding affinities between active components and core targets, with the stigmasterol-AKT1 complex exhibiting the lowest binding energy (-11.4 kcal/mol) and high stability in MD simulations. Validation using GEO datasets identified 12 core genes shared between CU-related targets and XQLD-associated targets, including PTGS2 and IL6, which were also prioritized as core targets in the network pharmacology analyses.

Discussion

This study comprehensively integrates multidisciplinary approaches to clarify the potential molecular mechanisms of XQLD in treating CU, highlighting its multitarget and multipathway synergistic effects. Molecular docking and dynamics simulations confirm the stable interaction between stigmasterol and the core target AKT1. Additionally, GEO dataset analysis verifies the pathogenic relevance of targets such as PTGS2 and IL6, significantly enhancing the credibility of our findings. These results provide a modern scientific basis for the traditional therapeutic effects of XQLD on CU and have important implications for developing multitarget treatments for this condition. However, this study mainly relies on database mining and computational simulations. Further in vitro and in vivo experimental validations are needed to confirm the predicted component-target-pathway interactions.

Conclusion

This study identifies the active components, potential targets, and pathways through which XQLD exerts therapeutic effects on CU. These findings provide a theoretical foundation for further mechanistic studies and support their clinical application in the treatment of CU.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cad/10.2174/0115734099391401250701045509
2025-07-16
2025-09-11

  • From This Site

    /content/journals/cad/10.2174/0115734099391401250701045509
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. He L. Yi W. Huang X. Long H. Lu Q. Chronic Urticaria: Advances in Understanding of the Disease and Clinical Management. Clin. Rev. Allergy Immunol. 2021 61 3 424 448 10.1007/s12016‑021‑08886‑x 34529248
    [Google Scholar]
  2. Kolkhir P. Giménez-Arnau A.M. Kulthanan K. Peter J. Metz M. Maurer M. Urticaria. Nat. Rev. Dis. Primers 2022 8 1 61 10.1038/s41572‑022‑00389‑z 36109590
    [Google Scholar]
  3. Sánchez-Borges M. Ansotegui I.J. Baiardini I. Bernstein J. Canonica G.W. Ebisawa M. Gomez M. Gonzalez-Diaz S.N. Martin B. Morais-Almeida M. Ortega Martell J.A. The challenges of chronic urticaria part 1: Epidemiology, immunopathogenesis, comorbidities, quality of life, and management. World Allergy Organ. J. 2021 14 6 100533 10.1016/j.waojou.2021.100533 34221215
    [Google Scholar]
  4. Zuberbier T. Balke M. Worm M. Edenharter G. Maurer M. Epidemiology of urticaria: A representative cross-sectional population survey. Clin. Exp. Dermatol. 2010 35 8 869 873 10.1111/j.1365‑2230.2010.03840.x 20456386
    [Google Scholar]
  5. Fricke J. Ávila G. Keller T. Weller K. Lau S. Maurer M. Zuberbier T. Keil T. Prevalence of chronic urticaria in children and adults across the globe: Systematic review with meta‐analysis. Allergy 2020 75 2 423 432 10.1111/all.14037 31494963
    [Google Scholar]
  6. Zuberbier T. Abdul Latiff A.H. Abuzakouk M. Aquilina S. Asero R. Baker D. Ballmer-Weber B. Bangert C. Ben-Shoshan M. Bernstein J.A. Bindslev-Jensen C. Brockow K. Brzoza Z. Chong Neto H.J. Church M.K. Criado P.R. Danilycheva I.V. Dressler C. Ensina L.F. Fonacier L. Gaskins M. Gáspár K. Gelincik A. Giménez-Arnau A. Godse K. Gonçalo M. Grattan C. Grosber M. Hamelmann E. Hébert J. Hide M. Kaplan A. Kapp A. Kessel A. Kocatürk E. Kulthanan K. Larenas-Linnemann D. Lauerma A. Leslie T.A. Magerl M. Makris M. Meshkova R.Y. Metz M. Micallef D. Mortz C.G. Nast A. Oude-Elberink H. Pawankar R. Pigatto P.D. Ratti Sisa H. Rojo Gutiérrez M.I. Saini S.S. Schmid-Grendelmeier P. Sekerel B.E. Siebenhaar F. Siiskonen H. Soria A. Staubach-Renz P. Stingeni L. Sussman G. Szegedi A. Thomsen S.F. Vadasz Z. Vestergaard C. Wedi B. Zhao Z. Maurer M. The international EAACI/GA2LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy 2022 77 3 734 766 10.1111/all.15090 34536239
    [Google Scholar]
  7. Eun S.J. Lee J.Y. Kim D.Y. Yoon H.S. Natural course of new-onset urticaria: Results of a 10-year follow-up, nationwide, population-based study. Allergol. Int. 2019 68 1 52 58 10.1016/j.alit.2018.05.011 29945815
    [Google Scholar]
  8. Tawil S. Irani C. Kfoury R. Abramian S. Salameh P. Weller K. Maurer M. Ezzedine K. Association of chronic urticaria with psychological distress: A multicentre cross-sectional study. Acta Derm. Venereol. 2023 103 adv00865 10.2340/actadv.v102.2939 36129251
    [Google Scholar]
  9. Gonçalo M. Gimenéz-Arnau A. Al-Ahmad M. Ben-Shoshan M. Bernstein J.A. Ensina L.F. Fomina D. Galvàn C.A. Godse K. Grattan C. Hide M. Katelaris C.H. Khoshkhui M. Kocatürk E. Kulthanan K. Medina I. Nasr I. Peter J. Staubach P. Wang L. Weller K. Maurer M. The global burden of chronic urticaria for the patient and society. Br. J. Dermatol. 2021 184 2 226 236 10.1111/bjd.19561 32956489
    [Google Scholar]
  10. Wedi B. Traidl S. Anti-IgE for the treatment of chronic urticaria. ImmunoTargets Ther. 2021 10 27 45 10.2147/ITT.S261416 33628747
    [Google Scholar]
  11. Elieh-Ali-Komi D. Metz M. Kolkhir P. Kocatürk E. Scheffel J. Frischbutter S. Terhorst-Molawi D. Fox L. Maurer M. Chronic urticaria and the pathogenic role of mast cells. Allergol. Int. 2023 72 3 359 368 10.1016/j.alit.2023.05.003 37210251
    [Google Scholar]
  12. Zuberbier T. Ensina L.F. Giménez-Arnau A. Grattan C. Kocatürk E. Kulthanan K. Kolkhir P. Maurer M. Chronic urticaria: Unmet needs, emerging drugs, and new perspectives on personalised treatment. Lancet 2024 404 10450 393 404 10.1016/S0140‑6736(24)00852‑3 39004090
    [Google Scholar]
  13. Fine L.M. Bernstein J.A. Guideline of chronic urticaria beyond. Allergy Asthma Immunol. Res. 2016 8 5 396 403 10.4168/aair.2016.8.5.396 27334777
    [Google Scholar]
  14. Johal K.J. Saini S.S. Current and emerging treatments for chronic spontaneous urticaria. Ann. Allergy Asthma Immunol. 2020 125 4 380 387 10.1016/j.anai.2019.08.465 31494233
    [Google Scholar]
  15. Yosipovitch G. Biazus Soares G. Mahmoud O. Current and emerging therapies for chronic spontaneous urticaria: A narrative review. Dermatol. Ther. 2023 13 8 1647 1660 10.1007/s13555‑023‑00972‑6 37386330
    [Google Scholar]
  16. Marín-Cabañas I. Berbegal-de Gracia L. de León-Marrero F. Hispán P. Silvestre J.F. Management of chronic spontaneous urticaria in routine clinical practice following the EAACI/GA(2)LEN/EDF/WAO guidelines. Actas Dermosifiliogr. 2017 108 4 346 353 10.1016/j.adengl.2017.03.014 28219634
    [Google Scholar]
  17. Li J. Han Y. Therapeutic effect of modified Xiaoqinglong Decoction on cough-variant asthma and immunological functioning in children. Am. J. Transl. Res. 2023 15 2 1360 1366 36915768
    [Google Scholar]
  18. Ren Y. Li X. Zhang Y. Yan Z. Xiaoqinglong decoction suppresses childhood cough variant asthma and inhibited the body inflammatory response by regulating IL-6/STAT3 signalling pathway. Ann. Med. Surg. 2023 85 11 5469 5477 10.1097/MS9.0000000000001326 37915641
    [Google Scholar]
  19. Wang L. Feng X. Wang B. Yang Y. Zhang T. Zhang X. Adjuvant treatment with xiaoqinglong formula for bronchial asthma in acute attack: A systematic review of randomized controlled trials. Evid. Based Complement. Alternat. Med. 2020 2020 1 8468219 10.1155/2020/8468219 33014114
    [Google Scholar]
  20. Wang L. Zheng X. Hui Y. Wang B. Yang Y. Feng X. Zhang T. Ma L. Zhang X. Adjuvant treatment with Xiaoqinglong formula for bronchial asthma. Medicine 2019 98 35 e17053 10.1097/MD.0000000000017053 31464965
    [Google Scholar]
  21. Yang H. Zhang C. Gan W. Chen J. Wu J. Xiao W. Yang Y. Zhao K. Sun Z. Xie X. Huang Q. A randomized controlled trial study protocol for Xiao-Qing-Long decoction in the treatment of refractory asthma. Medicine 2020 99 5 e18911 10.1097/MD.0000000000018911 32000396
    [Google Scholar]
  22. Zhang L. Yan J. Liu M. Hu J. Yu X. Fan A. Ren H. Effect of Minor Green-Blue Dragon Decoction on The Expression of IL-4, IFN-γ, IL-10 In The TSLP-Activated Dcs System. Zhonghua Zhongyiyao Xuekan 2018 36 6 1316 1319
    [Google Scholar]
  23. Liu W. Gu X. Treatment of chronic urticaria with Xiaoqinglong Decoction: A report of 19 cases. J. Dermatol. Venereol 1998 20 1 27 28
    [Google Scholar]
  24. Jiang L. Treatment of chronic urticaria with Xiaoqinglong Decoction: A case report. Contin Med. Educ. 2016 30 10 163 164
    [Google Scholar]
  25. Jia C. Li W. Liang Y. Han S. Experience of Han Shirong used Xiaoqinglong decoction to treat urticaria. Shaanxi J. Tradit Chin Med. 2023 44 8 1109 1112
    [Google Scholar]
  26. Sun J. Zhang A. Zhao J. Qin S. Analysis of the composition and indications of Xiaoqinglong Decoction. World Latest Med. Inform. 2019 19 93 278 279
    [Google Scholar]
  27. Zhang B. Zhao M. Clinical thinking and action mechanism analysis of Xiaoqinglong Decoction. Acta. Chin. Med. 2015 30 5 663 664
    [Google Scholar]
  28. Zhang P. Zhang D. Zhou W. Wang L. Wang B. Zhang T. Li S. Network pharmacology: Towards the artificial intelligence-based precision traditional Chinese medicine. Brief. Bioinform. 2023 25 1 bbad518 10.1093/bib/bbad518 38197310
    [Google Scholar]
  29. Pinzi L. Rastelli G. Molecular docking: Shifting paradigms in drug discovery. Int. J. Mol. Sci. 2019 20 18 4331 10.3390/ijms20184331 31487867
    [Google Scholar]
  30. Wu X. Xu L.Y. Li E.M. Dong G. Application of molecular dynamics simulation in biomedicine. Chem. Biol. Drug Des. 2022 99 5 789 800 10.1111/cbdd.14038 35293126
    [Google Scholar]
  31. Han X. Zhang A. Meng Z. Wang Q. Liu S. Wang Y. Tan J. Guo L. Li F. Bioinformatics analysis based on extracted ingredients combined with network pharmacology, molecular docking and molecular dynamics simulation to explore the mechanism of Jinbei oral liquid in the therapy of idiopathic pulmonary fibrosis. Heliyon 2024 10 18 e38173 10.1016/j.heliyon.2024.e38173 39364246
    [Google Scholar]
  32. Ru J. Li P. Wang J. Zhou W. Li B. Huang C. Li P. Guo Z. Tao W. Yang Y. Xu X. Li Y. Wang Y. Yang L. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform. 2014 6 1 13 10.1186/1758‑2946‑6‑13 24735618
    [Google Scholar]
  33. Li W.H. Han J.R. Ren P.P. Xie Y. Jiang D.Y. Exploration of the mechanism of Zisheng Shenqi decoction against gout arthritis using network pharmacology. Comput. Biol. Chem. 2021 90 107358 10.1016/j.compbiolchem.2020.107358 33243703
    [Google Scholar]
  34. UniProt Consortium T. UniProt: The universal protein knowledgebase. Nucleic Acids Res. 2018 46 5 2699 10.1093/nar/gky092 29425356
    [Google Scholar]
  35. Amberger J.S. Hamosh A. Searching online mendelian inheritance in man (OMIM): A knowledgebase of human genes and genetic phenotypes. Curr. Protoc Bioinformatics 2017 58 1 2.1 12 10.1002/cpbi.27 28654725
    [Google Scholar]
  36. Safran M. Dalah I. Alexander J. Rosen N. Iny Stein T. Shmoish M. Nativ N. Bahir I. Doniger T. Krug H. Sirota-Madi A. Olender T. Golan Y. Stelzer G. Harel A. Lancet D. GeneCards Version 3: The human gene integrator. Database 2010 2010 0 baq020 10.1093/database/baq020 20689021
    [Google Scholar]
  37. 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 10.1101/gr.1239303 14597658
    [Google Scholar]
  38. Bardou P. Mariette J. Escudié F. Djemiel C. Klopp C. jvenn: An interactive Venn diagram viewer. BMC Bioinformatics 2014 15 1 293 10.1186/1471‑2105‑15‑293 25176396
    [Google Scholar]
  39. Szklarczyk D. Gable A.L. Lyon D. Junge A. Wyder S. Huerta-Cepas J. Simonovic M. Doncheva N.T. Morris J.H. Bork P. Jensen L.J. Mering C. STRING v11: Protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019 47 D1 D607 D613 10.1093/nar/gky1131 30476243
    [Google Scholar]
  40. Jiao X. Sherman B.T. Huang D.W. Stephens R. Baseler M.W. Lane H.C. Lempicki R.A. DAVID-WS: A stateful web service to facilitate gene/protein list analysis. Bioinformatics 2012 28 13 1805 1806 10.1093/bioinformatics/bts251 22543366
    [Google Scholar]
  41. Chen L. Yang A. Li Y. Liu X. Jiang W. Hu K. Molecular mechanism of oroxyli semen against triple-negative breast cancer verified by bioinformatics and in vitro experiments. Medicine 2023 102 37 e34835 10.1097/MD.0000000000034835 37713894
    [Google Scholar]
  42. Kim S. Chen J. Cheng T. Gindulyte A. He J. He S. Li Q. Shoemaker B.A. Thiessen P.A. Yu B. Zaslavsky L. Zhang J. Bolton E.E. PubChem in 2021: New data content and improved web interfaces. Nucleic Acids Res. 2021 49 D1 D1388 D1395 10.1093/nar/gkaa971 33151290
    [Google Scholar]
  43. Kouranov A. Xie L. de la Cruz J. Chen L. Westbrook J. Bourne P.E. Berman H.M. The RCSB PDB information portal for structural genomics. Nucleic Acids Res. 2006 34 90001 D302 D305 10.1093/nar/gkj120 16381872
    [Google Scholar]
  44. Uhlenbrock N. Smith S. Weisner J. Landel I. Lindemann M. Le T.A. Hardick J. Gontla R. Scheinpflug R. Czodrowski P. Janning P. Depta L. Quambusch L. Müller M.P. Engels B. Rauh D. Structural and chemical insights into the covalent-allosteric inhibition of the protein kinase Akt. Chem. Sci. 2019 10 12 3573 3585 10.1039/C8SC05212C 30996949
    [Google Scholar]
  45. Li K. Cai J. Jiang Z. Meng Q. Meng Z. Xiao H. Chen G. Qiao C. Luo L. Yu J. Li X. Wei Y. Li H. Liu C. Shen B. Wang J. Feng J. Unveiling novel insights into human IL-6 − IL-6R interaction sites through 3D computer-guided docking and systematic site mutagenesis. Sci. Rep. 2024 14 1 18293 10.1038/s41598‑024‑69429‑w 39112658
    [Google Scholar]
  46. Oltersdorf T. Elmore S.W. Shoemaker A.R. Armstrong R.C. Augeri D.J. Belli B.A. Bruncko M. Deckwerth T.L. Dinges J. Hajduk P.J. Joseph M.K. Kitada S. Korsmeyer S.J. Kunzer A.R. Letai A. Li C. Mitten M.J. Nettesheim D.G. Ng S. Nimmer P.M. O’Connor J.M. Oleksijew A. Petros A.M. Reed J.C. Shen W. Tahir S.K. Thompson C.B. Tomaselli K.J. Wang B. Wendt M.D. Zhang H. Fesik S.W. Rosenberg S.H. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 2005 435 7042 677 681 10.1038/nature03579 15902208
    [Google Scholar]
  47. Lee D. Long S.A. Adams J.L. Chan G. Vaidya K.S. Francis T.A. Kikly K. Winkler J.D. Sung C.M. Debouck C. Richardson S. Levy M.A. DeWolf W.E. Keller P.M. Tomaszek T. Head M.S. Ryan M.D. Haltiwanger R.C. Liang P.H. Janson C.A. McDevitt P.J. Johanson K. Concha N.O. Chan W. Abdel-Meguid S.S. Badger A.M. Lark M.W. Nadeau D.P. Suva L.J. Gowen M. Nuttall M.E. Potent and selective nonpeptide inhibitors of caspases 3 and 7 inhibit apoptosis and maintain cell functionality. J. Biol. Chem. 2000 275 21 16007 16014 10.1074/jbc.275.21.16007 10821855
    [Google Scholar]
  48. De Savi C. Bradbury R.H. Rabow A.A. Norman R.A. de Almeida C. Andrews D.M. Ballard P. Buttar D. Callis R.J. Currie G.S. Curwen J.O. Davies C.D. Donald C.S. Feron L.J.L. Gingell H. Glossop S.C. Hayter B.R. Hussain S. Karoutchi G. Lamont S.G. MacFaul P. Moss T.A. Pearson S.E. Tonge M. Walker G.E. Weir H.M. Wilson Z. Optimization of a novel binding motif to (E)-3-(3,5-Difluoro-4-((1 R, 3 R)-2-(2-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1 H -pyrido[3,4- b]indol-1-yl)phenyl)acrylic acid (AZD9496), a potent and orally bioavailable selective estrogen receptor downregulator and antagonist. J. Med. Chem. 2015 58 20 8128 8140 10.1021/acs.jmedchem.5b00984 26407012
    [Google Scholar]
  49. Kinoshita T. Yoshida I. Nakae S. Okita K. Gouda M. Matsubara M. Yokota K. Ishiguro H. Tada T. Crystal structure of human mono-phosphorylated ERK1 at Tyr204. Biochem. Biophys. Res. Commun. 2008 377 4 1123 1127 10.1016/j.bbrc.2008.10.127 18983981
    [Google Scholar]
  50. Orsi D.L. Ferrara S.J. Siegel S. Friberg A. Bouché L. Pook E. Lienau P. Bluck J.P. Lemke C.T. Akcay G. Stellfeld T. Meyer H. Pütter V. Holton S.J. Korr D. Jerchel-Furau I. Pantelidou C. Strathdee C.A. Meyerson M. Eis K. Goldstein J.T. Discovery and characterization of orally bioavailable 4-chloro-6-fluoroisophthalamides as covalent PPARG inverse-agonists. Bioorg. Med. Chem. 2023 78 117130 10.1016/j.bmc.2022.117130 36542958
    [Google Scholar]
  51. Rowlinson S.W. Kiefer J.R. Prusakiewicz J.J. Pawlitz J.L. Kozak K.R. Kalgutkar A.S. Stallings W.C. Kurumbail R.G. Marnett L.J. A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385. J. Biol. Chem. 2003 278 46 45763 45769 10.1074/jbc.M305481200 12925531
    [Google Scholar]
  52. O’Connell J. Porter J. Kroeplien B. Norman T. Rapecki S. Davis R. McMillan D. Arakaki T. Burgin A. Fox D. Ceska T. Lecomte F. Maloney A. Vugler A. Carrington B. Cossins B.P. Bourne T. Lawson A. Small molecules that inhibit TNF signalling by stabilising an asymmetric form of the trimer. Nat. Commun. 2019 10 1 5795 10.1038/s41467‑019‑13616‑1 31857588
    [Google Scholar]
  53. Wilcken R. Liu X. Zimmermann M.O. Rutherford T.J. Fersht A.R. Joerger A.C. Boeckler F.M. Halogen-enriched fragment libraries as leads for drug rescue of mutant p53. J. Am. Chem. Soc. 2012 134 15 6810 6818 10.1021/ja301056a 22439615
    [Google Scholar]
  54. Toro-Domínguez D. Martorell-Marugán J. López-Domínguez R. García-Moreno A. González-Rumayor V. Alarcón-Riquelme M.E. Carmona-Sáez P. ImaGEO: Integrative gene expression meta-analysis from GEO database. Bioinformatics 2019 35 5 880 882 10.1093/bioinformatics/bty721 30137226
    [Google Scholar]
  55. Maurer M. Staubach P. Raap U. Richter-Huhn G. Baier-Ebert M. Chapman-Rothe N. ATTENTUS, a German online survey of patients with chronic urticaria highlighting the burden of disease, unmet needs and real-life clinical practice. Br. J. Dermatol. 2016 174 4 892 894 10.1111/bjd.14203 26406483
    [Google Scholar]
  56. Ertaş R. Erol K. Hawro T. Yılmaz H. Maurer M. Sexual functioning is frequently and markedly impaired in female patients with chronic spontaneous urticaria. J. Allergy Clin. Immunol. Pract. 2020 8 3 1074 1082 10.1016/j.jaip.2019.10.046 31751760
    [Google Scholar]
  57. Sánchez-Díaz M. Salazar-Nievas M.C. Molina-Leyva A. Arias-Santiago S. Risk factors of quality-of-life and sexual function impairment in chronic spontaneous urticaria patients: Cross-sectional study. Dermatology 2023 239 4 601 608 10.1159/000530518 37019095
    [Google Scholar]
  58. Park S.E. Sexual dysfunction in chronic urticaria: A systematic review. Dermatol. Ther. 2024 10.1007/s13555‑024‑01319‑5 39661249
    [Google Scholar]
  59. Khan S. Chopra C. Mitchell A. Nakonechna A. Yong P. Karim M.Y. Resistant chronic spontaneous urticaria – A case series narrative review of treatment options. Allergy Rhinol. 2022 13 21526575221144951 10.1177/21526575221144951 36578314
    [Google Scholar]
  60. Kolkhir P. Altrichter S. Munoz M. Hawro T. Maurer M. New treatments for chronic urticaria. Ann. Allergy Asthma Immunol. 2020 124 1 2 12 10.1016/j.anai.2019.08.014 31446134
    [Google Scholar]
  61. Gao Z. Jing J. Liu Y. Xiaoqinglong decoction (a traditional Chinese medicine) combined conventional treatment for acute exacerbation of chronic obstructive pulmonary disease. Medicine 2020 99 14 e19571 10.1097/MD.0000000000019571 32243375
    [Google Scholar]
  62. Huang Q. Yang H. Zhang C. Wu J. Xiao W. Zeng Z. Xiaoqinglong decoction protects the lungs of AECOPD mice through the AMPK/mTOR signaling pathway. Evid. Based Complement. Alternat. Med. 2020 2020 1 9865290 10.1155/2020/9865290 32714429
    [Google Scholar]
  63. Liu H.L. Chen H.F. Wu Y.D. Yan Y.J. He X.C. Li Z.Z. Ruan Y. Wu G.L. Xiaoqinglong decoction mitigates nasal inflammation and modulates gut microbiota in allergic rhinitis mice. Front. Microbiol. 2024 15 1290985 10.3389/fmicb.2024.1290985 38812686
    [Google Scholar]
  64. Ruan Y. Fan Y. Xie Y. Ma C. Mo B. Lai Y. Li G. Liu X. Kuang W. Modified Xiaoqinglong decoction alleviates lipopolysaccharide‐induced acute lung injury in mice by regulating arachidonic acid metabolism and exerting anti‐apoptotic and anti‐inflammatory effects. Anat. Rec. 2022 305 7 1672 1681 10.1002/ar.24822 34708578
    [Google Scholar]
  65. Wang R. Wang Y. Yang Q. Liu J. Lu Z. Xu W. Zhu J. Liu H. He W. Yan Y. Ruan Y. Zhou M. Xiaoqinglong decoction improves allergic rhinitis by inhibiting NLRP3-mediated pyroptosis in BALB/C mice. J. Ethnopharmacol. 2024 321 117490 10.1016/j.jep.2023.117490 38030025
    [Google Scholar]
  66. Billowria K. Ali R. Rangra N.K. Kumar R. Chawla P.A. Bioactive flavonoids: A comprehensive review on pharmacokinetics and analytical aspects. Crit. Rev. Anal. Chem. 2024 54 5 1002 1016 10.1080/10408347.2022.2105641 35930461
    [Google Scholar]
  67. Min Y.D. Choi C.H. Bark H. Son H.Y. Park H.H. Lee S. Park J.W. Park E.K. Shin H.I. Kim S.H. Quercetin inhibits expression of inflammatory cytokines through attenuation of NF-κB and p38 MAPK in HMC-1 human mast cell line. Inflamm. Res. 2007 56 5 210 215 10.1007/s00011‑007‑6172‑9 17588137
    [Google Scholar]
  68. Park H.H. Lee S. Son H.Y. Park S.B. Kim M.S. Choi E.J. Singh T.S.K. Ha J.H. Lee M.G. Kim J.E. Hyun M.C. Kwon T.K. Kim Y.H. Kim S.H. Flavonoids inhibit histamine release and expression of proinflammatory cytokines in mast cells. Arch. Pharm. Res. 2008 31 10 1303 1311 10.1007/s12272‑001‑2110‑5 18958421
    [Google Scholar]
  69. Shaik Y. Caraffa A. Ronconi G. Lessiani G. Conti P. Impact of polyphenols on mast cells with special emphasis on the effect of quercetin and luteolin. Cent. Eur. J. Immunol. 2018 43 4 476 481 10.5114/ceji.2018.81347 30799996
    [Google Scholar]
  70. Han N.R. Kim H.M. Jeong H.J. The potential anti-proliferative effect of β-sitosterol on human mast cell line-1 cells. Can. J. Physiol. Pharmacol. 2015 93 11 979 983 10.1139/cjpp‑2015‑0166 26314340
    [Google Scholar]
  71. Ma L. Ma Y. Liu Y. β-Sitosterol protects against food allergic response in BALB/c mice by regulating the intestinal barrier function and reconstructing the gut microbiota structure. Food Funct. 2023 14 10 4456 4469 10.1039/D3FO00772C 37066493
    [Google Scholar]
  72. Abd Rani N.Z. Kumolosasi E. Jasamai M. Jamal J.A. Lam K.W. Husain K. In vitro anti-allergic activity of Moringa oleifera Lam. extracts and their isolated compounds. BMC Complement. Altern. Med. 2019 19 1 361 10.1186/s12906‑019‑2776‑1 31829185
    [Google Scholar]
  73. Han N.R. Moon P.D. Ryu K.J. Kim N.R. Kim H.M. Jeong H.J. Inhibitory effect of naringenin via IL ‐13 level regulation on thymic stromal lymphopoietin‐induced inflammatory reactions. Clin. Exp. Pharmacol. Physiol. 2018 45 4 362 369 10.1111/1440‑1681.12880 29193236
    [Google Scholar]
  74. Moon P.D. Choi I.H. Kim H.M. Naringenin suppresses the production of thymic stromal lymphopoietin through the blockade of RIP2 and caspase-1 signal cascade in mast cells. Eur. J. Pharmacol. 2011 671 1-3 128 132 10.1016/j.ejphar.2011.09.163 21963452
    [Google Scholar]
  75. Murata K. Takano S. Masuda M. Iinuma M. Matsuda H. Anti-degranulating activity in rat basophil leukemia RBL-2H3 cells of flavanone glycosides and their aglycones in citrus fruits. J. Nat. Med. 2013 67 3 643 646 10.1007/s11418‑012‑0699‑y 22903244
    [Google Scholar]
  76. Chen K. Li Y. Zhang X. Ullah R. Tong J. Shen Y. The role of the PI3K/AKT signalling pathway in the corneal epithelium: recent updates. Cell Death Dis. 2022 13 5 513 10.1038/s41419‑022‑04963‑x 35641491
    [Google Scholar]
  77. Biethahn K. Orinska Z. Vigorito E. Goyeneche-Patino D.A. Mirghomizadeh F. Föger N. Bulfone-Paus S. mi RNA ‐155 controls mast cell activation by regulating the PI 3Kγ pathway and anaphylaxis in a mouse model. Allergy 2014 69 6 752 762 10.1111/all.12407 24734904
    [Google Scholar]
  78. Szydłowski M. Jabłońska E. Juszczyński P. FOXO1 transcription factor: A critical effector of the PI3K-AKT axis in B-cell development. Int. Rev. Immunol. 2014 33 2 146 157 10.3109/08830185.2014.885022 24552152
    [Google Scholar]
  79. Pompura S.L. Dominguez-Villar M. The PI3K/AKT signaling pathway in regulatory T-cell development, stability, and function. J. Leukoc. Biol. 2018 103 6 1065 1076 10.1002/JLB.2MIR0817‑349R 29357116
    [Google Scholar]
  80. Zhao J.W. Ping J.D. Wang Y.F. Liu X.N. Li N. Hu Z.L. Ming L. Vitamin D suppress the production of vascular endothelial growth factor in mast cell by inhibiting PI3K/Akt/p38 MAPK/HIF-1α pathway in chronic spontaneous urticaria. Clin. Immunol. 2020 215 108444 10.1016/j.clim.2020.108444 32339669
    [Google Scholar]
  81. Di Lorenzo A. Fernández-Hernando C. Cirino G. Sessa W.C. Akt1 is critical for acute inflammation and histamine-mediated vascular leakage. Proc. Natl. Acad. Sci. USA 2009 106 34 14552 14557 10.1073/pnas.0904073106 19622728
    [Google Scholar]
  82. Green B.D. Jabbour A.M. Sandow J.J. Riffkin C.D. Masouras D. Daunt C.P. Salmanidis M. Brumatti G. Hemmings B.A. Guthridge M.A. Pearson R.B. Ekert P.G. Akt1 is the principal Akt isoform regulating apoptosis in limiting cytokine concentrations. Cell Death Differ. 2013 20 10 1341 1349 10.1038/cdd.2013.63 23787999
    [Google Scholar]
  83. Su W. Tian Y. Wei Y. Hao F. Ji J. Key genes and immune infiltration in chronic spontaneous urticaria: A study of bioinformatics and systems biology. Front. Immunol. 2023 14 1279139 10.3389/fimmu.2023.1279139 38045687
    [Google Scholar]
  84. Rani S. Sharma P. Sharma P.K. Chitkara A. To evaluate the role and relevance of cytokines IL-17, IL-18, IL-23 and TNF-α and their correlation with disease severity in chronic urticaria. Indian Dermatol. Online J. 2020 11 4 594 597 10.4103/idoj.IDOJ_396_19 32832449
    [Google Scholar]
  85. Atwa M.A. Emara A.S. Youssef N. Bayoumy N.M. Serum concentration of IL ‐17, IL ‐23 and TNF ‐α among patients with chronic spontaneous urticaria: Association with disease activity and autologous serum skin test. J. Eur. Acad. Dermatol. Venereol. 2014 28 4 469 474 10.1111/jdv.12124 23451767
    [Google Scholar]
  86. Fang X. Weng Y. Zheng X. Involvement of CCL2 and CH25H Genes and TNF signaling pathways in mast cell activation and pathogenesis of chronic spontaneous urticaria. Front. Immunol. 2023 14 1247432 10.3389/fimmu.2023.1247432 37646031
    [Google Scholar]
  87. Tanaka M. Shirakura K. Takayama Y. Matsui M. Watanabe Y. Yamamoto T. Takahashi J. Tanaka S. Hino N. Doi T. Obana M. Fujio Y. Takayama K. Okada Y. Endothelial ROBO4 suppresses PTGS2/COX-2 expression and inflammatory diseases. Commun. Biol. 2024 7 1 599 10.1038/s42003‑024‑06317‑z 38762541
    [Google Scholar]
  88. Chen Y. Jian X. Zhu L. Yu P. Yi X. Cao Q. Wang J. Xiong F. Li J. PTGS2: A potential immune regulator and therapeutic target for chronic spontaneous urticaria. Life Sci. 2024 344 122582 10.1016/j.lfs.2024.122582 38514006
    [Google Scholar]
  89. Góra A. Przybył M. Świętochowska E. Machura E. Assessment of selected interleukins (IL-6, IL-17A, IL-18, IL-23) and chemokines (RANTES, IP-10) in children with acute and chronic urticaria. Ital. J. Pediatr. 2022 48 1 201 10.1186/s13052‑022‑01395‑3 36539847
    [Google Scholar]
  90. Kuna M. Štefanović M. Ladika Davidović B. Mandušić N. Birkić Belanović I. Lugović-Mihić L. Chronic urticaria biomarkers IL-6, ESR and CRP in correlation with disease severity and patient quality of life—A pilot study. Biomedicines 2023 11 8 2232 10.3390/biomedicines11082232 37626727
    [Google Scholar]
/content/journals/cad/10.2174/0115734099391401250701045509
Loading
Elucidating the Mechanism of Xiaoqinglong Decoction in Chronic Urticaria Treatment: An Integrated Approach of Network Pharmacology, Bioinformatics Analysis, Molecular Docking, and Molecular Dynamics Simulations
Bentham Science Publishers ; https://doi.org/10.2174/0115734099391401250701045509
/content/journals/cad/10.2174/0115734099391401250701045509
/content/journals/cad/10.2174/0115734099391401250701045509
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

file format download Download

  • Article Type:     Research Article
Keywords: network pharmacology ; Xiaoqinglong Decoction (XQLD) ; bioinformatics analysis ; molecular dynamics simulation ; molecular docking ; Chronic urticaria (CU)

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test