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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2019

Open Access 01-12-2019 | Bronchial Asthma | Research article

Inhibition of airway remodeling and inflammatory response by Icariin in asthma

Authors: Lingli Hu, Lulu Li, Hongying Zhang, Qiuping Li, Shan Jiang, Jian Qiu, Jing Sun, Jingcheng Dong

Published in: BMC Complementary Medicine and Therapies | Issue 1/2019

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Abstract

Background

Icariin (ICA) is the major active ingredient extracted from Chinese herbal medicine Epimedium, which has the effects of improving cardiovascular function, inducing tumor cell differentiation and increasing bone formation. It is still rarely reported that ICA can exert its therapeutic potential in asthma via anti-airway remodeling. The point of the study was to estimate the role of ICA in anti-.
airway remodeling and its possible mechanism of action in a mouse ovalbumin.
(OVA)-induced asthma model.

Methods

Hematoxylin and Eosin Staining were performed for measuring airway remodeling related indicators. ELISA, Western blot and Immunohistochemistr-.
y (IHC) were used for analyzing the level of protein. RT-PCR was used for analyzing the level of mRNA.

Results

On days 1 and 8, mice were sensitized to OVA by intraperitoneal injection. From day 16 to day 43, previously sensitized mice were exposed to OVA once daily by nebulizer. Interventions were performed orally with ICA (ICA low, medium and high dose groups) or dexamethasone 1 h prior to each OVA exposure. ICA improves pulmonary function, attenuates pulmonary inflammation and airway remodeling in mice exposed to OVA. Histological and Western blot analysis of the lungs show that ICA suppressed transforming growth factor beta 1 and vascular endothelial growth factor expression. Increase in interleukin 13 and endothelin-1 in serum and bronchoalveolar lavage fluid in OVA-induced asthmatic mice are also decreased by ICA. ICA attenuates airway smooth muscle cell proliferation, as well as key factors in the MAPK/Erk pathway.

Conclusions

The fact that ICA can alleviate OVA-induced asthma at least partly through inhibition of ASMC proliferation via MAPK/Erk pathway provides a solid theoretical basis for ICA as a replacement therapy for asthma. These data reveal the underlying reasons of the use of ICA-rich herbs in Traditional Chinese Medicine to achieve good results in treating asthma.
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Literature
1.
Halwani R, Al-Muhsen S, Hamid Q. Airway remodeling in asthma. Curr Opin Pharmacol. 2010;10(3):236–45.PubMedCrossRef
2.
3.
Homer RJ, Elias JA. Airway remodeling in asthma: therapeutic implications of mechanisms. Physiology (Bethesda). 2005;20:28–35.
4.
Michalik, M., et al., Asthmatic bronchial fibroblasts demonstrate enhanced potential to differentiate into myofibroblasts in culture. Med Sci Monit, 2009. 15(7): p. Br194–201.
5.
Ito I, et al. Platelet-derived growth factor and transforming growth factor-beta modulate the expression of matrix metalloproteinases and migratory function of human airway smooth muscle cells. Clin Exp Allergy. 2009;39(9):1370–80.PubMedCrossRef
6.
Clauss M. Molecular biology of the VEGF and the VEGF receptor family. Semin Thromb Hemost. 2000;26(5):561–9.PubMedCrossRef
7.
Hoshino M, Takahashi M, Aoike N. Expression of vascular endothelial growth factor, basic fibroblast growth factor, and angiogenin immunoreactivity in asthmatic airways and its relationship to angiogenesis. J Allergy Clin Immunol. 2001;107(2):295–301.PubMedCrossRef
8.
Lee YC, Lee HK. Vascular endothelial growth factor in patients with acute asthma. J Allergy Clin Immunol. 2001;107(6):1106.PubMedCrossRef
9.
Lee CG, et al. Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung. Nat Med. 2004;10(10):1095–103.PubMedPubMedCentralCrossRef
10.
Ammit AJ, Panettieri RA Jr. Airway smooth muscle cell hyperplasia: a therapeutic target in airway remodeling in asthma? Prog Cell Cycle Res. 2003;5:49–57.PubMed
11.
12.
Bjorck T, Gustafsson LE, Dahlen SE. Isolated bronchi from asthmatics are hyperresponsive to adenosine, which apparently acts indirectly by liberation of leukotrienes and histamine. Am Rev Respir Dis. 1992;145(5):1087–91.PubMedCrossRef
13.
Amrani Y, et al. Bronchial hyperresponsiveness: insights into new signaling molecules. Curr Opin Pharmacol. 2004;4(3):230–4.PubMedCrossRef
14.
Schuliga M, et al. Transforming growth factor-beta-induced differentiation of airway smooth muscle cells is inhibited by fibroblast growth factor-2. Am J Respir Cell Mol Biol. 2013;48(3):346–53.PubMedPubMedCentralCrossRef
15.
Doherty T, Broide D. Cytokines and growth factors in airway remodeling in asthma. Curr Opin Immunol. 2007;19(6):676–80.PubMedCrossRef
16.
Molet SM, Hamid QA, Hamilos DL. IL-11 and IL-17 expression in nasal polyps: relationship to collagen deposition and suppression by intranasal fluticasone propionate. Laryngoscope. 2003;113(10):1803–12.PubMedCrossRef
17.
Kelly, M.M., et al., Effects of budesonide and formoterol on allergen-induced airway responses, inflammation, and airway remodeling in asthma. J Allergy Clin Immunol, 2010. 125(2): p. 349–356.e13.
18.
Henderson WR Jr, et al. Reversal of allergen-induced airway remodeling by CysLT1 receptor blockade. Am J Respir Crit Care Med. 2006;173(7):718–28.PubMedCrossRef
19.
Oh YC, et al. Inhibitory effects of Epimedium herb on the inflammatory response in vitro and in vivo. Am J Chin Med. 2015;43(5):953–68.PubMedCrossRef
20.
Liu MH, et al. Icariin protects murine chondrocytes from lipopolysaccharide-induced inflammatory responses and extracellular matrix degradation. Nutr Res. 2010;30(1):57–65.PubMedCrossRef
21.
Sun S, et al. Icariin attenuates high glucose-induced apoptosis, oxidative stress, and inflammation in human umbilical venous endothelial cells. Planta Med. 2019;85(6):473–82.PubMedCrossRef
22.
Sun X, et al. Icariin inhibits LPS-induced cell inflammatory response by promoting GRalpha nuclear translocation and upregulating GRalpha expression. Life Sci. 2018;195:33–43.PubMedCrossRef
23.
Li C, et al. Pharmacological effects and pharmacokinetic properties of icariin, the major bioactive component in Herba Epimedii. Life Sci. 2015;126:57–68.PubMedCrossRef
24.
Li B, et al. Icariin attenuates glucocorticoid insensitivity mediated by repeated psychosocial stress on an ovalbumin-induced murine model of asthma. Int Immunopharmacol. 2014;19(2):381–90.PubMedCrossRef
25.
Xiong W, et al. Roles of the antioxidant properties of icariin and its phosphorylated derivative in the protection against duck virus hepatitis. BMC Vet Res. 2014;10:226.PubMedPubMedCentralCrossRef
26.
27.
28.
Wang YK, Huang ZQ. Protective effects of icariin on human umbilical vein endothelial cell injury induced by H2O2 in vitro. Pharmacol Res. 2005;52(2):174–82.PubMedCrossRef
29.
Song YH, et al. Icariin attenuated oxidative stress induced-cardiac apoptosis by mitochondria protection and ERK activation. Biomed Pharmacother. 2016;83:1089–94.PubMedCrossRef
30.
Xiang J, et al. Effect of icariin on hypoxia/reoxygenation injury in neonatal rat cardiomyocytes. Zhonghua Yi Xue Za Zhi. 2015;95(45):3701–4.PubMed
31.
Nie J, et al. Icariin inhibits beta-amyloid peptide segment 25-35 induced expression of beta-secretase in rat hippocampus. Eur J Pharmacol. 2010;626(2–3):213–8.PubMedCrossRef
32.
Sha D, et al. Icariin inhibits neurotoxicity of beta-amyloid by upregulating cocaine-regulated and amphetamine-regulated transcripts. Neuroreport. 2009;20(17):1564–7.PubMedCrossRef
33.
He W, et al. Immunoregulatory effects of the herba Epimediia glycoside icariin. Arzneimittelforschung. 1995;45(8):910–3.PubMed
34.
Zhao F, Tang YZ, Liu ZQ. Protective effect of icariin on DNA against radical-induced oxidative damage. J Pharm Pharmacol. 2007;59(12):1729–32.PubMedCrossRef
35.
Xiao HB, et al. Icariin regulates PRMT/ADMA/DDAH pathway to improve endothelial function. Pharmacol Rep. 2015;67(6):1147–54.PubMedCrossRef
36.
37.
Pichavant, M., et al., Animal models of airway sensitization. Curr Protoc Immunol, 2007. Chapter 15: p. Unit 15.18.
38.
Hu L, et al. Epigenetic regulation of interleukin 6 by histone acetylation in macrophages and its role in Paraquat-induced pulmonary fibrosis. Front Immunol. 2016;7:696.PubMed
39.
Zhang FQ, et al. Therapeutic efficacy of a co-blockade of IL-13 and IL-25 on airway inflammation and remodeling in a mouse model of asthma. Int Immunopharmacol. 2017;46:133–40.PubMedCrossRef
40.
Ntontsi P, et al. Targeted anti-IL-13 therapies in asthma: current data and future perspectives. Expert Opin Investig Drugs. 2018;27(2):179–86.PubMedCrossRef
41.
42.
Nishiyama, S.K., et al., Vascular function and endothelin-1: tipping the balance between vasodilation and vasoconstriction. J Appl Physiol (1985), 2017. 122(2): p. 354–360.PubMedCrossRef
43.
Janakidevi K, et al. Endothelin-1 stimulates DNA synthesis and proliferation of pulmonary artery smooth muscle cells. Am J Phys. 1992;263(6 Pt 1):C1295–301.CrossRef
44.
Zhang Y, Edvinsson L, Xu CB. Up-regulation of endothelin receptors induced by cigarette smoke--involvement of MAPK in vascular and airway hyper-reactivity. ScientificWorldJournal. 2010;10:2157–66.PubMedPubMedCentralCrossRef
45.
Gregory LG, et al. Endothelin-1 directs airway remodeling and hyper-reactivity in a murine asthma model. Allergy. 2013;68(12):1579–88.PubMedCrossRef
46.
Lan B, et al. Airway epithelial compression promotes airway smooth muscle proliferation and contraction. Am J Physiol Lung Cell Mol Physiol. 2018;315(5):L645–l652.PubMedPubMedCentralCrossRef
47.
Russell MA, et al. Differential effects of interleukin-13 and interleukin-6 on Jak/STAT signaling and cell viability in pancreatic beta-cells. Islets. 2013;5(2):95–105.PubMedPubMedCentralCrossRef
48.
49.
Dezateux C, Stocks J. Lung development and early origins of childhood respiratory illness. Br Med Bull. 1997;53(1):40–57.PubMedCrossRef
50.
Expert Panel Report 3 (EPR-3): Guidelines for the diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol, 2007 120(5 Suppl): p. S94–138.
51.
Opina MT, Moore WC. Phenotype-driven therapeutics in severe asthma. Curr Allergy Asthma Rep. 2017;17(2):10.PubMedCrossRef
52.
Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. American Thoracic Society. Am J Respir Crit Care Med, 2000. 162(6): p. 2341–2351.
53.
Shergis JL, et al. Herbal medicine for adults with asthma: a systematic review. J Asthma. 2016;53(6):650–9.PubMedCrossRef
54.
Gosens R, Grainge C. Bronchoconstriction and airway biology: potential impact and therapeutic opportunities. Chest. 2015;147(3):798–803.PubMedCrossRef
55.
Noble PB, et al. Airway smooth muscle in asthma: linking contraction and mechanotransduction to disease pathogenesis and remodelling. Pulm Pharmacol Ther. 2014;29(2):96–107.PubMedCrossRef
56.
O'Reilly, R., et al., Increased airway smooth muscle in preschool wheezers who have asthma at school age. J Allergy Clin Immunol, 2013. 131(4): p. 1024–32, 1032.e1–16.CrossRef
57.
Manuyakorn W, Howarth PH, Holgate ST. Airway remodelling in asthma and novel therapy. Asian Pac J Allergy Immunol. 2013;31(1):3–10.PubMed
58.
Kroegel C, et al. Endobronchial secretion of interleukin-13 following local allergen challenge in atopic asthma: relationship to interleukin-4 and eosinophil counts. Eur Respir J. 1996;9(5):899–904.PubMedCrossRef
59.
Gawlik R, et al. Concentration of endothelin in plasma and BALF fluid from asthmatic patients. J Physiol Pharmacol. 2006;57(Suppl 4):103–10.PubMed
60.
Sun Y, et al. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J Recept Signal Transduct Res. 2015;35(6):600–4.PubMedCrossRef
61.
Tang DD. Critical role of actin-associated proteins in smooth muscle contraction, cell proliferation, airway hyperresponsiveness and airway remodeling. Respir Res. 2015;16:134.PubMedPubMedCentralCrossRef
Metadata
Title
Inhibition of airway remodeling and inflammatory response by Icariin in asthma
Authors
Lingli Hu
Lulu Li
Hongying Zhang
Qiuping Li
Shan Jiang
Jian Qiu
Jing Sun
Jingcheng Dong
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2019
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-019-2743-x

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