Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

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

Author(s): Miaomiao Xie, Tingting Liu, Jie Yin, Jing Liu, Liu Yang, Ting Li, Chen Xia and Yanbo Fan*

Volume 27, Issue 1, 2024

Published on: 15 June, 2023

Page: [69 - 77] Pages: 9

DOI: 10.2174/1386207326666230503105935

open access plus

Abstract

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.

« Previous Next »
Graphical Abstract

[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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.3390/ijms20010123] [PMID: 30598019]
[6]
Grey, A.; Katelaris, C.H. Dupilumab in the treatment of asthma. Immunotherapy, 2019, 11(10), 859-872.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/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.
[http://dx.doi.org/10.1378/chest.122.5.1543] [PMID: 12426251]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy