Kechuanning Gel Plaster Exerts Anti-inflammatory and Immunomodulatory Effects on Ovalbumin-induced Asthma Model Rats via ERK Pathway


Цитировать

Полный текст

Аннотация

Background:We aimed to evaluate the therapeutic effects of Kechuanning gel plaster on ovalbumin (OVA)-induced rat model of asthma.

Methods:Rats were injected with OVA to induce asthma, and Kechuanning gel plaster was administered after the OVA challenge. The immune cell counts in the bronchial alveolar lavage fluid (BALF) were calculated after Kechuanning gel plaster administration. The levels of immune factors in BALF and serum OVA-specific IgE levels were analyzed. Western blot analysis and immunohistochemistry were carried out to analyze the following proteins: C-FOS, C-JUN, RAS p21 protein activator 1 (RASA1), matrix metalloproteinase 9 (MMP9), RAF1, p-MEK1, tissue inhibitor of metalloproteinase-1 (TIMP1), and p-extracellular signal-regulated kinase 1 (ERK1).

Results:Administration of Kechuanning gel plaster led to decreased immune cell counts, inflammatory cytokines (interleukin (IL)-1β, IL13, and IL17), and OVA-specific IgE expression. Compared to the normal group, the C-FOS, C-JUN, RASA1, MMP9, RAF1, MEK1, TIMP1, and p- ERK1 expressions in the model group were significantly increased, whereas Kechuanning gel plaster administration decreased C-JUN, MMP9, TIMP1, RAF1, MEK1, p-ERK1, C-FOS, and RASA1 protein levels.

Conclusion:Kechuanning gel plaster exerted its therapeutic effects on OVA-induced asthma model rats through the ERK signaling pathway. Kechuanning gel plaster could be considered as a potential alternative therapeutic agent for the management of asthma.

Об авторах

Miaomiao Xie

, Wuhan Hospital of Traditional Chinese Medicine,

Email: info@benthamscience.net

Tingting Liu

, Wuhan Hospital of Traditional Chinese Medicine

Email: info@benthamscience.net

Jie Yin

Wuhan, Hubei 430065, Hubei University of Chinese Medicine

Email: info@benthamscience.net

Jing Liu

, Wuhan Hospital of Traditional Chinese Medicin

Email: info@benthamscience.net

Liu Yang

, Wuhan Hospital of Traditional Chinese Medicine

Email: info@benthamscience.net

Ting Li

, Wuhan Hospital of Traditional Chinese Medicine

Email: info@benthamscience.net

Chen Xia

, Wuhan Hospital of Traditional Chinese Medicine

Email: info@benthamscience.net

Yanbo Fan

, Wuhan Hospital of Traditional Chinese Medicine

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

Список литературы

  1. Liu, F.; Shang, Y.X. Sirtuin 6 attenuates epithelial–mesenchymal transition by suppressing the TGF-β1/Smad3 pathway and c-Jun in asthma models. Int. Immunopharmacol., 2020, 82, 106333.
  2. Barcik, W.; Boutin, R.C.T.; Sokolowska, M.; Finlay, B.B. The role of lung and gut microbiota in the pathology of asthma. Immunity, 2020, 52(2), 241-255. doi: 10.1016/j.immuni.2020.01.007 PMID: 32075727
  3. Côté, A.; Godbout, K.; Boulet, L.P. The management of severe asthma in 2020. Biochem. Pharmacol., 2020, 179, 114112.
  4. Guo, M.; Liu, Y.; Han, X.; Han, F.; Zhu, J.; Zhu, S.; Chen, B. Tobacco smoking aggravates airway inflammation by upregulating endothelin-2 and activating the c-Jun amino terminal kinase pathway in asthma. Int. Immunopharmacol., 2019, 77, 10591.
  5. Frati, F.; Salvatori, C.; Incorvaia, C.; Bellucci, A.; Di Cara, G.; Marcucci, F.; Esposito, S. The role of the microbiome in asthma: The gut–lung axis. Int. J. Mol. Sci., 2018, 20(1), 123. doi: 10.3390/ijms20010123 PMID: 30598019
  6. Grey, A.; Katelaris, C.H. Dupilumab in the treatment of asthma. Immunotherapy, 2019, 11(10), 859-872. doi: 10.2217/imt-2019-0008 PMID: 31218914
  7. Gibson, P.G.; Yang, I.A.; Upham, J.W.; Reynolds, P.N.; Hodge, S.; James, A.L.; Jenkins, C.; Peters, M.J.; Marks, G.B.; Baraket, M.; Powell, H.; Taylor, S.L.; Leong, L.E.X.; Rogers, G.B.; Simpson, J.L. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet, 2017, 390(10095), 659-668. doi: 10.1016/S0140-6736(17)31281-3 PMID: 28687413
  8. Wang, J.; Wong, Y.K.; Liao, F. What has traditional Chinese medicine delivered for modern medicine? Expert Rev. Mol. Med., 2018, 20, e4.
  9. Du, H.Z.; Hou, X.Y.; Miao, Y.H.; Huang, B.S.; Liu, D.H. Traditional Chinese Medicine: an effective treatment for 2019 novel coronavirus pneumonia (NCP). Chin. J. Nat. Med., 2020, 18(3), 206-210. doi: 10.1016/S1875-5364(20)30022-4 PMID: 32245590
  10. Hempen, C.H.; Hummelsberger, J. Traditional Chinese medicine (TCM)—what is myth and what is the state of evidence today? Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz, 2020, 63(5), 570-576. doi: 10.1007/s00103-020-03132-9 PMID: 32266491
  11. Feng, Y.; Fang, Y.; Wang, Y.; Hao, Y. Acupoint therapy on diabetes mellitus and its common chronic complications: A review of its mechanisms. Biomed Res. Int., 2018, 2018, 3128378.
  12. Su, L.; Meng, L.; Chen, R.; Wu, W.; Peng, B.; Man, L. Acupoint application for asthma therapy in adults: A systematic review and meta-analysis of randomized controlled trials. Forsch. Komplementmed., 2016, 23(1), 16-21.
  13. Si, X.; Chen, S.; Guan, D.; Wang, J. The study of the effect on ige gerum of asthmatic rats treated with kechuanning paste. Gansu J. Trad. Chinese Med., 2007, 20(1), 2.
  14. Fan, Y.; Wang, W.; He, Z.; Li, J.; Ding, N.; Lu, L.; Zhang, J.; Xie, M. Transcriptome analysis of traditional chinese medicine ‘Kechuanning Plaster’ in the treatment of asthma. Comb. Chem. High Throughput Screen., 2023, 26(4), 778-788. PMID: 35611785
  15. Fan, Y.; Wang, W.; Du, X.; Wang, J. Optimization of matrix formula for qingre zhitong cataplasm. China Pharmacist., 2016, 19(4), 693-694.
  16. Sun, L.Z.; Elsayed, S.; Aasen, T.B.; Van Do, T.; Aardal, N.P.; Florvaag, E.; Vaali, K. Comparison between ovalbumin and ovalbumin peptide 323-339 responses in allergic mice: Humoral and cellular aspects. Scand. J. Immunol., 2010, 71(5), 329-335. doi: 10.1111/j.1365-3083.2010.02382.x PMID: 20500683
  17. Gao, P.; Zhao, Z.; Zhang, C.; Wang, C.; Long, K.; Guo, L.; Li, B. The therapeutic effects of traditional Chinese medicine Fusu agent in LPS-induced acute lung injury model rats. Drug Des. Devel. Ther., 2018, 12, 3867-3878.
  18. Li, W.J.; Zhao, Y.; Gao, Y.; Dong, L.L.; Wu, Y.F.; Chen, Z.H.; Shen, H.H. Lipid metabolism in asthma: Immune regulation and potential therapeutic target. Cell. Immunol., 2021, 364, 104341.
  19. Royer, D.J.; Cook, D.N. Regulation of immune responses by nonhematopoietic cells in asthma. Cell. Immunol., 2021, 364, 104341.
  20. Zhang, M.; Yu, Q.; Tang, W.; Wu, Y.; Lv, J.; Sun, L.; Shi, G.; Wu, M.; Qu, J.; Di, C.; Xia, Z. Epithelial exosomal contactin-1 promotes monocyte-derived dendritic cell–dominant T-cell responses in asthma. J. Allergy Clin. Immunol., 2021, 148(6), 1545-1558. doi: 10.1016/j.jaci.2021.04.025 PMID: 33957164
  21. Kishida, S.; Kato-Mori, Y.; Okamoto, M.; Hagiwara, K. Anti‐inflammatory effect a specific Lactiplantibacillus plantarum in an ovalbumin‐induced asthma model. Microbiol. Immunol., 2022, 66(9), 442-452. doi: 10.1111/1348-0421.13014 PMID: 35674213
  22. Östling, J.; van Geest, M.; Schofield, J.P.R.; Jevnikar, Z.; Wilson, S.; Ward, J.; Lutter, R.; Shaw, D.E.; Bakke, P.S.; Caruso, M.; Dahlen, S.E.; Fowler, S.J.; Horváth, I.; Krug, N.; Montuschi, P.; Sanak, M.; Sandström, T.; Sun, K.; Pandis, I.; Auffray, C.; Sousa, A.R.; Guo, Y.; Adcock, I.M.; Howarth, P.; Chung, K.F.; Bigler, J.; Sterk, P.J.; Skipp, P.J.; Djukanović, R.; Vaarala, O. IL-17–high asthma with features of a psoriasis immunophenotype. J. Allergy Clin. Immunol., 2019, 144(5), 1198-1213. doi: 10.1016/j.jaci.2019.03.027 PMID: 30998987
  23. Yang, N.; Shang, Y. Ferrostatin-1 and 3-methyladenine ameliorate ferroptosis in ova-induced asthma model and in il-13-challenged beas-2b cells. Oxid. Med. Cell. Longev., 2022, 2022, 9657933.
  24. Lommatzsch, M.; Geißler, K.; Bergmann, K.C.; Virchow, J.C. IgE and anti-IgE in asthma: A chequered history. Pneumologie, 2017, 71(6), 398-405. PMID: 28651294
  25. Yu, F.; Sun, Y.; Yu, J.; Ding, Z.; Wang, J.; Zhang, L.; Zhang, T.; Bai, Y.; Wang, Y. ORMDL3 is associated with airway remodeling in asthma via the ERK/MMP-9 pathway. Mol. Med. Rep., 2017, 15(5), 2969-2976. doi: 10.3892/mmr.2017.6413 PMID: 28358425
  26. Wang, W.; Xu, L.; Zhou, L.; Wan, S.; Jiang, L. Dioscorea nipponica Makino relieves ovalbumin-induced asthma in mice through regulating RKIP-mediated Raf-1/MEK/MAPK/ERK signaling pathway. Biomed Res. Int., 2022, 2022, 8077058.
  27. Feng, L.; Su, J.; Chi, R.; Zhu, Q.; Lv, S.; Liang, W. Effect of amlodipine besylate combined with acupoint application of traditional Chinese medicine nursing on the treatment of renal failure and hypertension by the PI3K/AKT pathway. Int. J. Mol. Med., 2019, 43(4), 1900-1910. doi: 10.3892/ijmm.2019.4104 PMID: 30816438
  28. Ricciardolo, F.L.M.; Sorbello, V.; Silvestri, M.; Giacomelli, M.; Debenedetti, V.M.G.; Malerba, M.; Ciprandi, G.; Rossi, G.A.; Rossi, A.; Bontempelli, M. TNF-alpha, IL-4R-alpha and IL-4 polymorphisms in mild to severe asthma from Italian Caucasians. Int. J. Immunopathol. Pharmacol., 2013, 26(1), 75-84. doi: 10.1177/039463201302600107 PMID: 23527710
  29. Doherty, T.; Broide, D. Cytokines and growth factors in airway remodeling in asthma. Curr. Opin. Immunol., 2007, 19(6), 676-680. doi: 10.1016/j.coi.2007.07.017 PMID: 17720466
  30. Ramakrishnan, R.K.; Al Heialy, S.; Hamid, Q. Role of IL-17 in asthma pathogenesis and its implications for the clinic. Expert Rev. Respir. Med., 2019, 13(11), 1057-1068. doi: 10.1080/17476348.2019.1666002 PMID: 31498708
  31. Han, M.W.; Kim, S.H.; Oh, I.; Kim, Y.H.; Lee, J. Serum IL-1β can be a biomarker in children with severe persistent allergic rhinitis. Allergy Asthma Clin. Immunol., 2019, 15, 58.
  32. Li, P.; Li, Z.; Zhang, G.; Yang, J.; Chen, J. CD4+CD25+ regulatory T cells decreased CD8+IL-4+cellsin a mouse model of allergic asthma. Iran. J. Allergy Asthma Immunol., 2019, 18(4), 369-378. doi: 10.18502/ijaai.v18i4.1415 PMID: 31522445
  33. Barnes, P.J. Immunology of asthma and chronic obstructive pulmonary disease. Nat. Rev. Immunol., 2008, 8(3), 183-192. doi: 10.1038/nri2254 PMID: 18274560
  34. Wang, J.; Shang, Y.X.; Cai, X.X.; Liu, L.Y. Vasoactive intestinal peptide inhibits airway smooth muscle cell proliferation in a mouse model of asthma via the ERK1/2 signaling pathway. Exp. Cell Res., 2018, 364(2), 168-174. doi: 10.1016/j.yexcr.2018.01.042 PMID: 29408536
  35. Xie, M.; Liu, X.S.; Xu, Y.J.; Zhang, Z.X.; Bai, J.; Ni, W.; Chen, S.X. ERK1/2 signaling pathway modulates the airway smooth muscle cell phenotype in the rat model of chronic asthma. Respiration, 2007, 74(6), 680-690. doi: 10.1159/000108783 PMID: 17890845
  36. Zhang, Y.; Bian, C.; Wu, J.; Zhao, J.; Wang, J.; Liu, T.; Liu, L.; Dong, L. (IL-33 promotes airway remodeling in a mouse model of asthma via ERK1/2 signaling pathway). Xibao Yu Fenzi Mianyixue Zazhi, 2016, 32(5), 590-594. PMID: 27126934
  37. Degirmenci, U.; Wang, M.; Hu, J. Targeting aberrant RAS/RAF/MEK/ERK signaling for cancer therapy. Cells, 2020, 9(1), 198. doi: 10.3390/cells9010198 PMID: 31941155
  38. Asati, V.; Mahapatra, D.K.; Bharti, S.K. PI3K/Akt/mTOR and Ras/Raf/MEK/ERK signaling pathways inhibitors as anticancer agents: Structural and pharmacological perspectives. Eur. J. Med. Chem., 2016, 109, 314-341.
  39. Janson, N.D.; Jehanathan, N.; Jung, S.; Priyathilaka, T.T.; Nam, B.H.; Kim, M.J.; Lee, J. Insight into the molecular function and transcriptional regulation of activator protein 1 (AP-1) components c-Jun/c-Fos ortholog in red lip mullet (Liza haematocheila). Fish Shellfish Immunol., 2019, 93, 597-611.
  40. Nguyen, C.; Teo, J.L.; Matsuda, A.; Eguchi, M.; Chi, E.Y.; Henderson, W.R., Jr; Kahn, M. Chemogenomic identification of Ref-1/AP-1 as a therapeutic target for asthma. Proc. Natl. Acad. Sci. USA, 2003, 100(3), 1169-1173. doi: 10.1073/pnas.0437889100 PMID: 12552119
  41. Desmet, C.; Gosset, P.; Henry, E.; Garzé, V.; Faisca, P.; Vos, N.; Jaspar, F.; Mélotte, D.; Lambrecht, B.; Desmecht, D.; Pajak, B.; Moser, M.; Lekeux, P.; Bureau, F. Treatment of experimental asthma by decoy-mediated local inhibition of activator protein-1. Am. J. Respir. Crit. Care Med., 2005, 172(6), 671-678. doi: 10.1164/rccm.200410-1431OC PMID: 15961692
  42. Gueders, M.M.; Foidart, J.M.; Noel, A.; Cataldo, D.D. Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: Potential implications in asthma and other lung diseases. Eur. J. Pharmacol., 2006, 533(1-3), 133-144. doi: 10.1016/j.ejphar.2005.12.082 PMID: 16487964
  43. Vignola, A.M.; Riccobono, L.; Mirabella, A.; Profita, M.; Chanez, P.; Bellia, V.; Mautino, G.; D’Accardi, P.; Bousquet, J.; Bonsignore, G. Sputum metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis. Am. J. Respir. Crit. Care Med., 1998, 158(6), 1945-1950. doi: 10.1164/ajrccm.158.6.9803014 PMID: 9847290
  44. Mattos, W.; Lim, S.; Russell, R.; Jatakanon, A.; Chung, K.F.; Barnes, P.J. Matrix metalloproteinase-9 expression in asthma: effect of asthma severity, allergen challenge, and inhaled corticosteroids. Chest, 2002, 122(5), 1543-1552. doi: 10.1378/chest.122.5.1543 PMID: 12426251

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML

© Bentham Science Publishers, 2024