Skip to content
2000
Volume 28, Issue 18
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Purpose

The Yiqi Wenyang Huwei Decoction (YWHD) is an herbal formula frequently utilized to treat asthma. Despite its wide usage, the specific mechanism of action remains unknown. Through an in-depth investigation utilizing network pharmacology, molecular docking techniques, and experimental validation, this study aims to uncover the molecular mechanism and material basis of YWHD in the treatment of asthma.

Methods

The compounds and targets of YWHD were gathered from various databases such as TCMSP, PubMed, and CNKI. Additionally, asthma-related targets were obtained by combining the GEO dataset with GeneCards and OMIM databases. The STRING platform was employed to establish protein-protein interactions. GO and KEGG pathway enrichment analyses were conducted using DAVID. Molecular docking was utilized to assess the binding affinity between potential targets and active compounds. The asthma rat model was established through OVA induction, and a lung function meter was used to detect Mch-induced Max Rrs. HE staining was conducted to observe pathological changes, while ELISA was used to detect levels of inflammatory factors IL4, IL6, IL13, and IgE in BLAF. Furthermore, qPCR was used to detect levels of IL-1β, IL-6, JUN, and PTGS2 mRNA, while Western blot assay was employed to measure phosphorylation levels of NF-κB and IKKα.

Results

A comprehensive study revealed that YWHD has 188 active compounds and 250 corresponding targets. After conducting a topological analysis of the PPI network, the study identified 14 high-activity targets, including JUN, PTGS2, IL6, IL1B, CXCL8, MMP9, IL10, ALB, TGFB1, CCL2, IFNG, IL4, MAPK3, and STAT3. Further, GO and KEGG pathway enrichment analysis indicated that YWHD targets inflammation-related genes and regulates IL-17 and NF-kappa B signaling pathways. Animal studies have shown that YWHD can effectively minimize airway Max Rrs, reduce the levels of inflammatory factors IL4, IL13, IL6, and IgE in BLAF, and improve airway inflammation in rats with asthma. Molecular experiments have also demonstrated that YWHD achieves this by down-regulating the expression levels of IL-1β, IL-6, JUN, and PTGS2 mRNA, inhibiting the phosphorylation modification levels of NF-κB and IKKα, and reducing the levels of inflammatory cytokines IL4, IL13, IL6, and IgE in BALF of rats. Interestingly, molecular docking has revealed that the active compounds in YWHD have a strong binding ability to the screening targets.

Conclusion

This research endeavor systematically explicated the active constituents, prospective targets, and signaling pathways of YWHD for asthmatic intervention. The study provides an innovative notion and dependable resource for comprehending the molecular mechanism and pharmaceutical screening of YWHD in the context of asthma treatment.

This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/cchts/10.2174/0113862073293081240606111739
2024-11-28
2025-12-17
Loading full text...

Full text loading...

/deliver/fulltext/cchts/28/18/CCHTS-28-18-02.html?itemId=/content/journals/cchts/10.2174/0113862073293081240606111739&mimeType=html&fmt=ahah

References

  1. El-HusseiniZ.W. GosensR. DekkerF. KoppelmanG.H. The genetics of asthma and the promise of genomics-guided drug target discovery.Lancet Respir. Med.20208101045105610.1016/S2213‑2600(20)30363‑5 32910899
    [Google Scholar]
  2. McIntyreA. BusseW.W. Asthma exacerbations: The Achilles heel of asthma care.Trends Mol. Med.202228121112112710.1016/j.molmed.2022.09.001 36208987
    [Google Scholar]
  3. HuangK. YangT. XuJ. YangL. ZhaoJ. ZhangX. BaiC. KangJ. RanP. ShenH. WenF. ChenY. SunT. ShanG. LinY. XuG. WuS. WangC. WangR. ShiZ. XuY. YeX. SongY. WangQ. ZhouY. LiW. DingL. WanC. YaoW. GuoY. XiaoF. LuY. PengX. ZhangB. XiaoD. WangZ. ChenZ. BuX. ZhangH. ZhangX. AnL. ZhangS. ZhuJ. CaoZ. ZhanQ. YangY. LiangL. TongX. DaiH. CaoB. WuT. ChungK.F. HeJ. WangC. Prevalence, risk factors, and management of asthma in China: A national cross-sectional study.Lancet20193941019640741810.1016/S0140‑6736(19)31147‑X 31230828
    [Google Scholar]
  4. LinJ. WangW. TangH. HuoJ. GuY. LiuR. ChenP. YuanY. YangX. XuJ. SunD. LiN. JiangS. ChenY. WangC. YangL. LiuX. YangD. ZhangW. ChenZ. LinQ. LiuC. ZhouJ. ZhouX. HuC. JiangP. ZhouW. ZhangJ. CaiS. QiuC. HuangM. HuangY. LiuH. Asthma management using the mobile asthma evaluation and management system in China.Allergy Asthma Immunol. Res.2022141859810.4168/aair.2022.14.1.85 34983109
    [Google Scholar]
  5. RabyK.L. MichaeloudesC. TonkinJ. ChungK.F. BhavsarP.K. Mechanisms of airway epithelial injury and abnormal repair in asthma and COPD.Front. Immunol.202314120165810.3389/fimmu.2023.1201658 37520564
    [Google Scholar]
  6. PotaczekD.P. MietheS. SchindlerV. AlhamdanF. GarnH. Role of airway epithelial cells in the development of different asthma phenotypes.Cell. Signal.20206910952310.1016/j.cellsig.2019.109523 31904412
    [Google Scholar]
  7. KhanM.A. Regulatory T cells mediated immunomodulation during asthma: A therapeutic standpoint.J. Transl. Med.202018145610.1186/s12967‑020‑02632‑1 33267824
    [Google Scholar]
  8. JiT. LiH. T-helper cells and their cytokines in pathogenesis and treatment of asthma.Front. Immunol.202314114920310.3389/fimmu.2023.1149203 37377958
    [Google Scholar]
  9. NabeT. Steroid-resistant asthma and neutrophils.Biol. Pharm. Bull.2020431313510.1248/bpb.b19‑00095 31902928
    [Google Scholar]
  10. LambrechtB.N. HammadH. FahyJ.V. The Cytokines of Asthma.Immunity201950497599110.1016/j.immuni.2019.03.018
    [Google Scholar]
  11. HudeyS.N. LedfordD.K. CardetJ.C. Mechanisms of non-type 2 asthma.Curr. Opin. Immunol.20206612312810.1016/j.coi.2020.10.002 33160187
    [Google Scholar]
  12. BrownM.A. JabeenM. BharjG. HinksT.S.C. Non-typeable Haemophilus influenzae airways infection: The next treatable trait in asthma?Eur. Respir. Rev.20223116522000810.1183/16000617.0008‑2022 36130784
    [Google Scholar]
  13. KermaniN. VersiA. GayA. VlasmaJ. JayalathaA.K.S. KoppelmanG.H. NawijnM. FaizA. van den BergeM. AdcockI.M. ChungK.F. Gene signatures in U-BIOPRED severe asthma for molecular phenotyping and precision medicine: Time for clinical use.Expert Rev. Respir. Med.2023171196597110.1080/17476348.2023.2278606 37997709
    [Google Scholar]
  14. XiangS.D. YuQ.Q. YuJ.W. YuT. YeC. XueH.R. Study on the mechanism of prevention and treatment of asthma by the method of benefiting qi for warming yang and protecting defensive qi based on the signaling pathway of mTOR-mediated autophagy.Zhonghua Zhongyiyao Zazhi20213667756777
    [Google Scholar]
  15. YuQ.Q. BaoM.J. YuT. YuJ.W. SunP. YeC. XueH.R. Effect of Yiqi Wenyang Huwei Decoction on IL-6/STAT3 signaling pathway in Th17 cells of asthmatic rats.Zhonghua Zhongyiyao Zazhi20213649944997
    [Google Scholar]
  16. YuT. DingM. YuQ.Q. YuJ.W. YeC. SunP. XueH.R. Effects of Yiqi Wenyang Huwei Decoction on lung tissue inflammation and intestinal flora in asthmatic rats.Zhonghua Zhongyiyao Zazhi20223719241928
    [Google Scholar]
  17. HuoM.Q. PengS. RenY. ShuZ. ZhangY.L. QiaoY.J. Discovery and application of Chinese medicine efficacy markers based on systematic herbalism.Zhongguo Zhongyao Zazhi2020453245325010.19540/j.cnki.cjcmm.20200210.402 32726036
    [Google Scholar]
  18. ChanH.H.L. NgT. Traditional chinese medicine (TCM) and allergic diseases.Curr. Allergy Asthma Rep.202020116710.1007/s11882‑020‑00959‑9 32875353
    [Google Scholar]
  19. ChenY. WangJ. WuL. ZhangY. ChenH. ZhangZ. Efficacy of Chinese herbal medicine on nasal itching in children with allergic rhinitis: A systematic review and meta-analysis.Front. Pharmacol.202314124091710.3389/fphar.2023.1240917 37680707
    [Google Scholar]
  20. ChenY.J. Shimizu BassiG. WangY. YangY.Q. Research hotspot and frontier analysis of traditional Chinese medicine in asthma using bibliometric methods from 1991 to 2021.J. Allergy Clin. Immunol. Glob.20221418519710.1016/j.jacig.2022.07.004 37779535
    [Google Scholar]
  21. WangW. YaoQ. TengF. CuiJ. DongJ. WeiY. Active ingredients from Chinese medicine plants as therapeutic strategies for asthma: Overview and challenges.Biomed. Pharmacother.202113711138310.1016/j.biopha.2021.111383 33761604
    [Google Scholar]
  22. MaY. ZhouK. FanJ. SunS. Traditional Chinese medicine: Potential approaches from modern dynamical complexity theories.Front. Med.2016101283210.1007/s11684‑016‑0434‑2 26809465
    [Google Scholar]
  23. ChengL.H. ChenL.Y. ShouB.Y. LuoY.Y. CuiY.R. LiuR.H. Molecular mechanism of Dalbergia cochinchinensis heartwood in regulation of energy metabolism to treat myocardial ischemia based on network pharmacology and experimental validation.Zhongguo Zhongyao Zazhi202247246696670810.19540/j.cnki.cjcmm.20220902.702 36604920
    [Google Scholar]
  24. ZhaoL. ZhangH. LiN. ChenJ. XuH. WangY. LiangQ. Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula.J. Ethnopharmacol.202330911630610.1016/j.jep.2023.116306 36858276
    [Google Scholar]
  25. ZhangP. ZhangD. ZhouW. WangL. WangB. ZhangT. LiS. Network pharmacology: Towards the artificial intelligence-based precision traditional Chinese medicine.Brief. Bioinform.2023251bbad51810.1093/bib/bbad518 38197310
    [Google Scholar]
  26. JinD. ZhangJ. ZhangY. AnX. ZhaoS. DuanL. ZhangY. ZhenZ. LianF. TongX. Network pharmacology-based and molecular docking prediction of the active ingredients and mechanism of ZaoRenDiHuang capsules for application in insomnia treatment.Comput. Biol. Med.202113510456210.1016/j.compbiomed.2021.104562 34174759
    [Google Scholar]
  27. LiuZ.W. LuoZ.H. MengQ.Q. ZhongP.C. HuY.J. ShenX.L. Network pharmacology-based investigation on the mechanisms of action of Morinda officinalis How. in the treatment of osteoporosis.Comput. Biol. Med.202012710407410.1016/j.compbiomed.2020.104074 33126122
    [Google Scholar]
  28. YangH.Y. LiuM.L. LuoP. YaoX.S. ZhouH. Network pharmacology provides a systematic approach to understanding the treatment of ischemic heart diseases with traditional Chinese medicine.Phytomedicine202210415426810.1016/j.phymed.2022.154268 35777118
    [Google Scholar]
  29. RuJ. LiP. WangJ. ZhouW. LiB. HuangC. LiP. GuoZ. TaoW. YangY. XuX. LiY. WangY. YangL. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines.J. Cheminform.2014611310.1186/1758‑2946‑6‑13 24735618
    [Google Scholar]
  30. XuX. ZhangW. HuangC. LiY. YuH. WangY. DuanJ. LingY. A novel chemometric method for the prediction of human oral bioavailability.Int. J. Mol. Sci.20121366964698210.3390/ijms13066964 22837674
    [Google Scholar]
  31. BanC. JoM. ParkY.H. KimJ.H. HanJ.Y. LeeK.W. KweonD.H. ChoiY.J. Enhancing the oral bioavailability of curcumin using solid lipid nanoparticles.Food Chem.202030212532810.1016/j.foodchem.2019.125328 31404868
    [Google Scholar]
  32. GrothE.E. WeberM. BahmerT. PedersenF. KirstenA. BörnigenD. RabeK.F. WatzH. AmmerpohlO. GoldmannT. Exploration of the sputum methylome and omics deconvolution by quadratic programming in molecular profiling of asthma and COPD: The road to sputum omics 2.0.Respir. Res.202021127410.1186/s12931‑020‑01544‑4 33076907
    [Google Scholar]
  33. O’BeirneS.L. SalitJ. KanerR.J. CrystalR.G. Strulovici-BarelY. Up-regulation of ACE2, the SARS-CoV-2 receptor, in asthmatics on maintenance inhaled corticosteroids.Respir. Res.202122120010.1186/s12931‑021‑01782‑0 34233672
    [Google Scholar]
  34. GuS. XueY. GaoY. ShenS. ZhangY. ChenK. XueS. PanJ. TangY. ZhuH. WuH. DouD. Mechanisms of indigo naturalis on treating ulcerative colitis explored by GEO gene chips combined with network pharmacology and molecular docking.Sci. Rep.20201011520410.1038/s41598‑020‑71030‑w 32938944
    [Google Scholar]
  35. RebhanM. Chalifa-CaspiV. PriluskyJ. LancetD. GeneCards: Integrating information about genes, proteins and diseases.Trends Genet.199713416310.1016/S0168‑9525(97)01103‑7 9097728
    [Google Scholar]
  36. AmbergerJ.S. BocchiniC.A. SchiettecatteF. ScottA.F. HamoshA. OMIM.org: Online mendelian inheritance in man (OMIM®), an online catalog of human genes and genetic disorders.Nucleic Acids Res.201543D1D789D79810.1093/nar/gku1205 25428349
    [Google Scholar]
  37. SzklarczykD. GableA.L. NastouK.C. LyonD. KirschR. PyysaloS. DonchevaN.T. LegeayM. FangT. BorkP. JensenL.J. von MeringC. The STRING database in 2021: Customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets.Nucleic Acids Res.202149D1D605D61210.1093/nar/gkaa1074 33237311
    [Google Scholar]
  38. ShannonP. MarkielA. OzierO. BaligaN.S. WangJ.T. RamageD. AminN. SchwikowskiB. IdekerT. Cytoscape: A software environment for integrated models of biomolecular interaction networks.Genome Res.200313112498250410.1101/gr.1239303 14597658
    [Google Scholar]
  39. SongW. NiS. FuY. WangY. Uncovering the mechanism of Maxing Ganshi Decoction on asthma from a systematic perspective: A network pharmacology study.Sci. Rep.2018811736210.1038/s41598‑018‑35791‑9 30478434
    [Google Scholar]
  40. ChinC.H. ChenS.H. WuH.H. HoC.W. KoM.T. LinC.Y. cytoHubba: Identifying hub objects and sub-networks from complex interactome.BMC Syst. Biol.20148S4Suppl. 4S1110.1186/1752‑0509‑8‑S4‑S11 25521941
    [Google Scholar]
  41. LiuJ. WuS. XieX. WangZ. LeiQ. Identification of potential crucial genes and key pathways in osteosarcoma.Hereditas202015712910.1186/s41065‑020‑00142‑0 32665038
    [Google Scholar]
  42. HuangD.W. ShermanB.T. LempickiR.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.Nat. Protoc.200941445710.1038/nprot.2008.211 19131956
    [Google Scholar]
  43. RobinsonM.D. McCarthyD.J. SmythG.K. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data.Bioinformatics201026113914010.1093/bioinformatics/btp616 19910308
    [Google Scholar]
  44. GoodsellD.S. ZardeckiC. Di CostanzoL. DuarteJ.M. HudsonB.P. PersikovaI. SeguraJ. ShaoC. VoigtM. WestbrookJ.D. YoungJ.Y. BurleyS.K. RCSB protein data bank: Enabling biomedical research and drug discovery, protein sci.Publ. Protein Soc.2020295265
    [Google Scholar]
  45. StierandK. MaaßP.C. RareyM. Molecular complexes at a glance: Automated generation of two-dimensional complex diagrams.Bioinformatics200622141710171610.1093/bioinformatics/btl150 16632493
    [Google Scholar]
  46. FrickerP.C. GastreichM. RareyM. Automated drawing of structural molecular formulas under constraints.J. Chem. Inf. Comput. Sci.20044431065107810.1021/ci049958u 15154775
    [Google Scholar]
  47. PademN. SaltounC. Classification of asthma.Allergy Asthma Proc.201940638538810.2500/aap.2019.40.4253 31690376
    [Google Scholar]
  48. ZhouB. LiuH. JiaX. The role and mechanisms of traditional chinese medicine for airway inflammation and remodeling in asthma: Overview and progress.Front. Pharmacol.20221391725610.3389/fphar.2022.917256 35910345
    [Google Scholar]
  49. ZhangY. WangX. ZhangH. TangH. HuH. WangS. WongV.K.W. LiY. DengJ. Autophagy modulators from chinese herbal medicines: Mechanisms and therapeutic potentials for asthma.Front. Pharmacol.20211271067910.3389/fphar.2021.710679 34366865
    [Google Scholar]
  50. MengZ. ChenH. DengC. MengS. Potential cellular endocrinology mechanisms underlying the effects of Chinese herbal medicine therapy on asthma.Front. Endocrinol.20221391632810.3389/fendo.2022.916328 36051395
    [Google Scholar]
  51. LiJ. ZhangF. LiJ. The immunoregulatory effects of traditional chinese medicine on treatment of asthma or asthmatic inflammation.Am. J. Chin. Med.20154361059108110.1142/S0192415X15500615 26364661
    [Google Scholar]
  52. LiS. Framework and practice of network-based studies for Chinese herbal formula.J. Chin. Integr. Med.20075548949310.3736/jcim20070501 17854545
    [Google Scholar]
  53. WangY. ChenY.J. XiangC. JiangG.W. XuY.D. YinL.M. ZhouD.D. LiuY.Y. YangY.Q. Discovery of potential asthma targets based on the clinical efficacy of Traditional Chinese Medicine formulas.J. Ethnopharmacol.202025211263510.1016/j.jep.2020.112635 32004629
    [Google Scholar]
  54. LiuJ.X. ZhangY. YuanH.Y. LiangJ. The treatment of asthma using the Chinese Materia Medica.J. Ethnopharmacol.202126911355810.1016/j.jep.2020.113558 33186702
    [Google Scholar]
  55. LiS. ZhangB. Traditional Chinese medicine network pharmacology: Theory, methodology and application.Chin. J. Nat. Med.201311211012010.1016/S1875‑5364(13)60037‑0 23787177
    [Google Scholar]
  56. XuJ. YuZ. LiW. Kaempferol inhibits airway inflammation induced by allergic asthma through NOX4-Mediated autophagy.Hum. Exp. Toxicol.20234210.1177/09603271231154227 36803065
    [Google Scholar]
  57. RajizadehM.A. BejeshkM.A. DoustimotlaghA.H. NajafipourH. EftekhariM. MahmoodiM. AziziM. RostamabadiF. PourghadamyariH. The alleviating impacts of quercetin on inflammation and oxidant-antioxidant imbalance in rats with allergic asthma.Iran. J. Allergy Asthma Immunol.202322213814910.18502/ijaai.v22i2.12675 37496407
    [Google Scholar]
  58. HuangX. ShenQ.K. GuoH.Y. LiX. QuanZ.S. Pharmacological overview of hederagenin and its derivatives.RSC Med. Chem.202314101858188410.1039/D3MD00296A 37859723
    [Google Scholar]
  59. XuJ. YangL. LinT. β-sitosterol targets glucocorticoid receptor to reduce airway inflammation and remodeling in allergic asthma.Pulm. Pharmacol. Ther.20237810218310.1016/j.pupt.2022.102183 36481301
    [Google Scholar]
  60. AntwiA.O. ObiriD.D. OsafoN. Stigmasterol modulates allergic airway inflammation in guinea pig model of ovalbumin-induced asthma.Mediators Inflamm.20172017295393010.1155/2017/2953930
    [Google Scholar]
  61. ChenS. ChenZ. DengY. ZhaS. YuL. LiD. LiangZ. YangK. LiuS. ChenR. Prevention of IL-6 signaling ameliorates toluene diisocyanate-induced steroid-resistant asthma.Allergol. Int.2022711738210.1016/j.alit.2021.07.004 34332882
    [Google Scholar]
  62. WeiW. HuangJ. MaY. MaX. FangL. FangW. HaoC. IL‐1 signaling pathway molecules as key markers in childhood asthma.Pediatr. Allergy Immunol.202132230531310.1111/pai.13388 33025692
    [Google Scholar]
  63. DavisR.J. Signal transduction by the JNK group of MAP kinases.Cell2000103223925210.1016/S0092‑8674(00)00116‑1 11057897
    [Google Scholar]
  64. ZekeA. MishevaM. ReményiA. BogoyevitchM.A. SignalingJ.N.K. JNK signaling: Regulation and functions based on complex protein-protein partnerships.Microbiol. Mol. Biol. Rev.201680379383510.1128/MMBR.00043‑14 27466283
    [Google Scholar]
  65. BaoC. LiuC. LiuQ. HuaL. HuJ. LiZ. XuS. Liproxstatin-1 alleviates LPS/IL-13-induced bronchial epithelial cell injury and neutrophilic asthma in mice by inhibiting ferroptosis.Int. Immunopharmacol.202210910877010.1016/j.intimp.2022.108770 35483233
    [Google Scholar]
  66. SongJ. ZhangH. TongY. WangY. XiangQ. DaiH. WengC. WangL. FanJ. ShuaiY. LaiC. FangX. ChenM. BaoJ. ZhangW. Molecular mechanism of interleukin-17A regulating airway epithelial cell ferroptosis based on allergic asthma airway inflammation.Redox Biol.20236810297010.1016/j.redox.2023.102970 38035662
    [Google Scholar]
  67. VicovanA.G. PetrescuD.C. CretuA. GhiciucC.M. ConstantinescuD. IftimiE. StrugariuG. AncutaC.M. CaratașuC.C. SolcanC. StafieC.S. Targeting common inflammatory mediators in experimental severe asthma and acute lung injury.Pharmaceuticals202417333810.3390/ph17030338 38543124
    [Google Scholar]
  68. TullyJ.E. HoffmanS.M. LahueK.G. NolinJ.D. AnathyV. LundbladL.K.A. DaphtaryN. AliyevaM. BlackK.E. DixonA.E. PoynterM.E. IrvinC.G. Janssen-HeiningerY.M.W. Epithelial NF-κB orchestrates house dust mite-induced airway inflammation, hyperresponsiveness, and fibrotic remodeling.J. Immunol.2013191125811582110.4049/jimmunol.1301329 24227776
    [Google Scholar]
/content/journals/cchts/10.2174/0113862073293081240606111739
Loading
/content/journals/cchts/10.2174/0113862073293081240606111739
Loading

Data & Media loading...

Supplements

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

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