Integration of metabolomics and transcriptomics reveals the therapeutic mechanism underlying Chelidonium majus L. in the treatment of allergic asthma.
Chelidonium majus L
Allergic asthma
Energy metabolism
Inflammation
Metabolomics
Transcriptomics
Journal
Chinese medicine
ISSN: 1749-8546
Titre abrégé: Chin Med
Pays: England
ID NLM: 101265109
Informations de publication
Date de publication:
26 Apr 2024
26 Apr 2024
Historique:
received:
06
07
2023
accepted:
07
04
2024
medline:
27
4
2024
pubmed:
27
4
2024
entrez:
26
4
2024
Statut:
epublish
Résumé
Chelidonium majus is a well-known traditional Chinese medicine, and has been reported of the effect in relieving cough and asthma. However, the mechanism of action is still unknown. Asthmatic SD rats were first sensitized and established through ovalbumin (OVA) motivation. Subsequently, Hematoxylin and eosin (H&E) staining, Masson's trichrome (Masson) staining, Periodic acid-Schiff (PAS) staining and inflammatory cytokines assay of interleukin (IL)-4, IL-6, IL-17 were implemented to evaluate the protective effects of Chelidonium majus on asthma. Then, the effects of Chelidonium majus and their molecular mechanisms of action on asthma were detected based on the integration of transcriptomics and metabolomics analyses. After administration with Chelidonium majus, the histological injuries of inflammation, collagen deposition and mucus secretion in lungs were attenuated and the serum inflammatory cytokines perturbations were also converted. Furthermore, integrated analysis revealed that after Chelidonium majus treatment, 7 different expression genes (DEGs) (Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9) and 9 metabolic biomarkers (ADP, Xanthosine, Hypoxanthine, Inosine, prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a), phosphatidylserine, Creatine and LysoPC (10:0)) were discovered to be connected with the enrichment metabolic pathways, including Purine metabolism, Arachidonic acid metabolism, Arginine and proline metabolism and Glycerophospholipid metabolism. The obtained metabolic biomarkers and DEGs were mainly related to energy metabolism and inflammation, and may be potential therapeutic targets. Chelidonium majus relieved OVA-induced asthma in rats by regulating the Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9 genes expression to restore the disorders in energy metabolism and inflammation.
Sections du résumé
BACKGROUND
BACKGROUND
Chelidonium majus is a well-known traditional Chinese medicine, and has been reported of the effect in relieving cough and asthma. However, the mechanism of action is still unknown.
METHODS
METHODS
Asthmatic SD rats were first sensitized and established through ovalbumin (OVA) motivation. Subsequently, Hematoxylin and eosin (H&E) staining, Masson's trichrome (Masson) staining, Periodic acid-Schiff (PAS) staining and inflammatory cytokines assay of interleukin (IL)-4, IL-6, IL-17 were implemented to evaluate the protective effects of Chelidonium majus on asthma. Then, the effects of Chelidonium majus and their molecular mechanisms of action on asthma were detected based on the integration of transcriptomics and metabolomics analyses.
RESULTS
RESULTS
After administration with Chelidonium majus, the histological injuries of inflammation, collagen deposition and mucus secretion in lungs were attenuated and the serum inflammatory cytokines perturbations were also converted. Furthermore, integrated analysis revealed that after Chelidonium majus treatment, 7 different expression genes (DEGs) (Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9) and 9 metabolic biomarkers (ADP, Xanthosine, Hypoxanthine, Inosine, prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a), phosphatidylserine, Creatine and LysoPC (10:0)) were discovered to be connected with the enrichment metabolic pathways, including Purine metabolism, Arachidonic acid metabolism, Arginine and proline metabolism and Glycerophospholipid metabolism. The obtained metabolic biomarkers and DEGs were mainly related to energy metabolism and inflammation, and may be potential therapeutic targets.
CONCLUSION
CONCLUSIONS
Chelidonium majus relieved OVA-induced asthma in rats by regulating the Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9 genes expression to restore the disorders in energy metabolism and inflammation.
Identifiants
pubmed: 38671520
doi: 10.1186/s13020-024-00932-y
pii: 10.1186/s13020-024-00932-y
doi:
Types de publication
Journal Article
Langues
eng
Pagination
65Subventions
Organisme : Jilin Scientific and Technological Development Program
ID : 192485YY010358427
Informations de copyright
© 2024. The Author(s).
Références
Holgate ST, Davies DE, Powell RM, Howarth PH, Haitchi HM, Holloway JW. Local genetic and environmental factors in asthma disease pathogenesis: chronicity and persistence mechanisms. Eur Respir J. 2007;29(4):793–803. https://doi.org/10.1183/09031936.00087506 .
doi: 10.1183/09031936.00087506
pubmed: 17400878
Zhang Y, Jing Y, Qiao J, Luan B, Wang X, Wang L, et al. Activation of the mTOR signaling pathway is required for asthma onset. Sci Rep. 2017;7(1):4532. https://doi.org/10.1038/s41598-017-04826-y .
doi: 10.1038/s41598-017-04826-y
pmcid: 5495772
pubmed: 28674387
Gillissen A, Paparoupa M. Inflammation and infections in asthma. Clin Respir J. 2015;9(3):257–69. https://doi.org/10.1111/crj.12135 .
doi: 10.1111/crj.12135
pubmed: 24725460
Corren J. Role of interleukin-13 in asthma. Curr Allergy Asthma Rep. 2013;13(5):415–20. https://doi.org/10.1007/s11882-013-0373-9 .
doi: 10.1007/s11882-013-0373-9
pubmed: 24026573
Erle DJ, Sheppard D. The cell biology of asthma. J Cell Biol. 2014;205(5):621–31. https://doi.org/10.1083/jcb.201401050 .
doi: 10.1083/jcb.201401050
pmcid: 4050726
pubmed: 24914235
Ji NF, Xie YC, Zhang MS, Zhao X, Cheng H, Wang H, et al. Ligustrazine corrects Th1/Th2 and Treg/Th17 imbalance in a mouse asthma model. Int Immunopharmacol. 2014;21(1):76–81. https://doi.org/10.1016/j.intimp.2014.04.015 .
doi: 10.1016/j.intimp.2014.04.015
pubmed: 24785327
Mukherjee AA, Kandhare AD, Rojatkar SR, Bodhankar SL. Ameliorative effects of Artemisia pallens in a murine model of ovalbumin-induced allergic asthma via modulation of biochemical perturbations. Biomed Pharmacother. 2017;94:880–9. https://doi.org/10.1016/j.biopha.2017.08.017 .
doi: 10.1016/j.biopha.2017.08.017
pubmed: 28810518
Bateman ED, Hurd SS, Barnes PJ, Bousquet J, Drazen JM, FitzGerald JM, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J. 2008;31(1):143–78. https://doi.org/10.1183/13993003.51387-2007 .
doi: 10.1183/13993003.51387-2007
pubmed: 18166595
Chapoval SP, García LN, Leimgruber C, Nicola JP, Quintar AA, Maldonado CA. Neonatal endotoxin stimulation is associated with a long-term bronchiolar epithelial expression of innate immune and anti-allergic markers that attenuates the allergic response. PloS One. 2020;15(5): e0226233. https://doi.org/10.1371/journal.pone.0226233 .
doi: 10.1371/journal.pone.0226233
Ji W, Zhang Q, Shi H, Dong R, Ge D, Du X, et al. The mediatory role of Majie cataplasm on inflammation of allergic asthma through transcription factors related to Th1 and Th2. Chin Med. 2020;24(15):53. https://doi.org/10.1186/s13020-020-00334-w .
doi: 10.1186/s13020-020-00334-w
Hsu WH, Lin LJ, Lu CK, Kao ST, Lin YL. Effect of You-Gui-Wan on house dust mite-induced mouse allergic asthma via regulating amino acid metabolic disorder and gut dysbiosis. Biomolecules. 2021;11(6):821. https://doi.org/10.3390/biom11060812 .
doi: 10.3390/biom11060812
Chinese Pharmacopoeia Commission. Pharmacopoeia of the People’s Republic of China. Beijing: China Medical Science Press; 2020. p. 292.
Park JE, Cuong TD, Hung TM, Lee I, Na M, Kim JC, et al. Alkaloids from Chelidonium majus and their inhibitory effects on LPS-induced NO production in RAW264.7 cells. Bioorg Med Chem Lett. 2011;21(23):6960–3. https://doi.org/10.1016/j.bmcl.2011.09.128 .
doi: 10.1016/j.bmcl.2011.09.128
pubmed: 22024033
Kuenzel J, Geisler K, Strahl O, Grundtner P, Beckmann MW, Dittrich R. Chelidonium majus and its effects on uterine contractility in a perfusion model. Eur J Obstet Gynecol Reprod Biol. 2013;169(2):213–7. https://doi.org/10.1016/j.ejogrb.2013.03.014 .
doi: 10.1016/j.ejogrb.2013.03.014
pubmed: 23608627
Pan J, Yang Y, Zhang R, Yao H, Ge K, Zhang M, et al. Enrichment of chelidonine from chelidonium majus l. using macroporous resin and its antifungal activity. J Chromatography B. 2017;1070:7–14. https://doi.org/10.1016/j.jchromb.2017.10.029 .
doi: 10.1016/j.jchromb.2017.10.029
Yu M, Cui FX, Jia HM, Zhou C, Yang Y, Zhang HW, et al. Aberrant purine metabolism in allergic asthma revealed by plasma metabolomics. J Pharm Biomed Anal. 2016;120:181–9. https://doi.org/10.1016/j.jpba.2015.12.018 .
doi: 10.1016/j.jpba.2015.12.018
pubmed: 26744988
Ho WE, Xu YJ, Xu F, Cheng C, Peh HY, Tannenbaum SR, et al. Metabolomics reveals altered metabolic pathways in experimental asthma. Am J Respir Cell Mol Biol. 2013;48(2):204–11. https://doi.org/10.1165/rcmb.2012-0246OC .
doi: 10.1165/rcmb.2012-0246OC
pmcid: 5455591
pubmed: 23144334
Zelena E, Dunn WB, Broadhurst D, Francis-McIntyre S, Carroll KM, Begley P, et al. Development of a robust and repeatable UPLC-MS method for the long-term metabolomic study of human serum. Anal Chem. 2009;81(4):1357–64. https://doi.org/10.1021/ac8019366 .
doi: 10.1021/ac8019366
pubmed: 19170513
Want EJ, Masson P, Michopoulos F, Wilson ID, Theodoridis G, Plumb RS, et al. Global metabolic profiling of animal and human tissues via UPLC-MS. Nat Protoc. 2013;8(1):17–32. https://doi.org/10.1038/nprot.2012.135 .
doi: 10.1038/nprot.2012.135
pubmed: 23222455
Liu LW, Xing QQ, Zhao X, Tan M, Lu Y, Dong YM, et al. Proteomic analysis provides insights into the therapeutic effect of GU-BEN-FANG-XIAO decoction on a persistent asthmatic mouse model. Front Pharmacol. 2019;10:441. https://doi.org/10.3389/fphar.2019.00441 .
doi: 10.3389/fphar.2019.00441
pmcid: 6514195
pubmed: 31133848
Xing QQ, Liu LW, Zhao X, Lu Y, Dong YM, Liang ZQ. Serum proteomics analysis based on label-free revealed the protective effect of Chinese herbal formula Gu-Ben-Fang-Xiao. Biomed Pharmacother. 2019;119:109390. https://doi.org/10.1016/j.biopha.2019.109390 .
doi: 10.1016/j.biopha.2019.109390
pubmed: 31520916
Lim JCW, Goh FY, Sagineedu SR, Yong ACH, Sidik SM, Lajis NH, et al. A semisynthetic diterpenoid lactone inhibits NF-κB signalling to ameliorate inflammation and airway hyperresponsiveness in a mouse asthma model. Toxicol Appl Pharmacol. 2016;302:10–22. https://doi.org/10.1016/j.taap.2016.04.004 .
doi: 10.1016/j.taap.2016.04.004
pubmed: 27089844
Kim MS, Radinger M, Gilfillan AM. The multiple roles of phosphoinositide 3-kinase in mast cell biology. Trends Immunol. 2008;29(10):493–501. https://doi.org/10.1016/j.it.2008.07.004 .
doi: 10.1016/j.it.2008.07.004
pmcid: 2706663
pubmed: 18775670
Fruman DA, Bismuth G. Fine tuning the immune response with PI3K. Immunol Rev. 2009;228(1):253–72. https://doi.org/10.1111/j.1600-065X.2008.00750.x .
doi: 10.1111/j.1600-065X.2008.00750.x
pubmed: 19290933
Thomas M, Edwards MJ, Sawicka E, Duggan N, Hirsch E, Wymann MP, et al. Essential role of phosphoinositide 3-kinase gamma in eosinophil chemotaxis within acute pulmonary inflammation. Immunol. 2009;126(3):413–22. https://doi.org/10.1111/j.1365-2567.2008.02908.x .
doi: 10.1111/j.1365-2567.2008.02908.x
Yang CM, Lee IT, Lin CC, Yang YL, Luo SF, Kou YR, et al. Cigarette smoke extract induces COX-2 expression via a PKCalpha/c-Src/EGFR, PDGFR/PI3K/Akt/NF-kappaB pathway and p300 in tracheal smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2009;297(5):L892-902. https://doi.org/10.1152/ajplung.00151.2009 .
doi: 10.1152/ajplung.00151.2009
pubmed: 19717552
Kawahara K, Hohjoh H, Inazumi T, Tsuchiya S, Sugimoto Y. Prostagl and in E2-induced inflammation: Relevance of prostaglandin e receptors. Biochim Biophys Acta. 2015;1851(4):414–21. https://doi.org/10.1016/j.bbalip.2014.07.008 .
doi: 10.1016/j.bbalip.2014.07.008
pubmed: 25038274
Rogerio AP, Dora CL, Andrade EL, Chaves JS, Silva LF, Lemos-Senna E, et al. Anti-inflammatory effect of quercetin-loaded microemulsion in the airways allergic inflammatory model in mice. Pharmacol Res. 2010;61(4):288–97. https://doi.org/10.1016/j.phrs.2009.10.005 .
doi: 10.1016/j.phrs.2009.10.005
pubmed: 19892018
Eltzschig HK. Adenosine: an old drug newly discovered. Anesthesiology. 2009;111(4):904–15. https://doi.org/10.1097/ALN.0b013e3181b060f2 .
doi: 10.1097/ALN.0b013e3181b060f2
pubmed: 19741501
Xu X, Li J, Zhang Y, Zhang L. Arachidonic acid 15-Lipoxygenase: effects of its expression, metabolites, and genetic and epigenetic variations on airway inflammation. Allergy Asthma Immunol Res. 2021;13(5):684–96. https://doi.org/10.4168/aair.2021.13.5.684 .
doi: 10.4168/aair.2021.13.5.684
pmcid: 8419644
pubmed: 34486255
Basu S. Bioactive eicosanoids: role of prostagl and in F2α and F2-isoprostanes in inflammation and oxidative stress related pathology. Mol Cells. 2010;30(5):383–91. https://doi.org/10.1007/s10059-010-0157-1 .
doi: 10.1007/s10059-010-0157-1
pubmed: 21113821
Kwang Je, Baek Jae, Youn Cho, et al. Hypoxia potentiates allergen induction of HIF-1α chemokines, airway inflammation, TGF-β1, and airway remodeling in a mouse model. Clin Immunol. 2013;147:27–37. https://doi.org/10.1016/j.clim.2013.02.004 .
doi: 10.1016/j.clim.2013.02.004
Tsuge K, Inazumi T, Shimamoto A, Sugimoto Y. Molecular mechanisms underlying prostaglandin E2-exacerbated inflammation and immune diseases. Int Immunol. 2019;31(9):597–606. https://doi.org/10.1093/intimm/dxz021 .
doi: 10.1093/intimm/dxz021
pubmed: 30926983
Kang YP, Lee WJ, Hong JY, Lee SB, Park JH, Kim D, et al. Novel approach for analysis of bronchoalveolar lavage fluid (BALF) using HPLC-QTOF-MS-based lipidomics: lipid levels in asthmatics and corticosteroid-treated asthmatic patients. J Proteome Res. 2014;13(9):3919–29. https://doi.org/10.1021/pr5002059 .
doi: 10.1021/pr5002059
pubmed: 25040188
Chang C, Guo ZG, He B, Yao WZ. Metabolic alterations in the sera of Chinese patients with mild persistent asthma: a GC-MS-based metabolomics analysis. Acta Pharmacol Sin. 2015;36(11):1356–66. https://doi.org/10.1038/aps.2015.102 .
doi: 10.1038/aps.2015.102
pmcid: 4635323
pubmed: 26526201
Izquierdo-Garcia JL, Nin N, Ruiz-Cabello J, Rojas Y, de Paula M, Lopez-Cuenca S, et al. A metabolomic approach for diagnosis of experimental sepsis. Intensive Care Med. 2011;37(12):2023–32. https://doi.org/10.1007/s00134-011-2359-1 .
doi: 10.1007/s00134-011-2359-1
pubmed: 21976186
Yu M, Cui FX, Jia HM, Zhou C, Yang Y, Zhang HW, et al. Aberrant purine metabolism in allergic asthma revealed by plasma metabolomics. J Pharm Biomed Anal. 2016;120:181–9. https://doi.org/10.1016/j.jpba.2015.12.018 .
doi: 10.1016/j.jpba.2015.12.018
pubmed: 26744988