Main Article Content
Curcumol, asthma, PDGF-BB, ERK/CREB pathway, airway smooth muscle cells
Background: Curcumol, possessing antiviral, antifungal, antimicrobial, anticancer, and anti-inflammatory properties, has been widely used in treating cancers and liver fibrosis. The aim of this study was to determine the effect of curcumol on the progression of asthma.
Materials and methods: Curcumol was administrated to platelet-derived growth factor (PDGF)-BB-stimulated airway smooth muscle cells (ASMCs). The proliferation of ASMCs was assessed by MTT and EdU incorporation assays. The apoptosis of ASMCs was measured by flow cytometry and Western blotting. The migration of ASMCs was evaluated by Transwell migration assay and Western blotting. The regulatory effects of curcumol on extracellular signal-regulated protein kinase (ERK)/cAMP response element-binding protein (CREB) pathway was evaluated by Western blotting.
Results: The proliferation and migration of ASMCs induced by PDGF-BB was suppressed, and the apoptosis of ASMCs was elevated by curcumol in a dose-dependent manner. The activation of ERK/CREB pathway induced by PDGF-BB was suppressed by curcumol.
Conclusion: Curcumol could suppress ERK/CREB pathway to inhibit proliferation and migration and promote apoptosis of PDGF-BB-stimulated ASMCs. These findings suggest that curcumol may act as a potential drug for asthma treatment.
2. Wu TD, Brigham EP, McCormack MC. Asthma in the primary care setting. Med Clin North Am. 2019;103(3):435–52. 10.1016/j.mcna.2018.12.004
3. Tanaka K, Arakawa M, Miyake Y. Perinatal smoking exposure and risk of asthma in the first three years of life: A prospective prebirth cohort study. Allergologia et Immunopathologia. 2020;48(6):530–6. 10.1016/j.aller.2020.03.008
4. Boulet LP, Boulay M. Asthma-related comorbidities. Exp Rev Resp Med. 2011;5(3):377–93. 10.1586/ers.11.34
5. Liu G, Cooley MA, Nair PM, Donovan C, Hsu AC, Jarnicki AG, et al. Airway remodelling and inflammation in asthma are dependent on the extracellular matrix protein fibulin-1c. J Pathol. 2017;243(4):510–23. 10.1002/path.4979
6. Yeganeh B, Xia C, Movassagh H, Koziol-White C, Chang Y, Al-Alwan L, et al. Emerging mediators of airway smooth muscle dysfunction in asthma. Pulm Pharmacol Ther. 2013;26(1):105–11. 10.1016/j.pupt.2012.06.011
7. Redhu NS, Shan L, Movassagh H, Gounni AS. Thymic stromal lymphopoietin induces migration in human airway smooth muscle cells. Sci Rep. 2013;3:2301. 10.1038/srep02301
8. Salter B, Pray C, Radford K, Martin JG, Nair P. Regulation of human airway smooth muscle cell migration and relevance to asthma. Respir Res. 2017;18(1):156. 10.1186/s12931-017-0640-8
9. Zhao L, Shi X, Wang N, Liu C, Wang J. YAP1, targeted by miR-375, enhanced the pro-angiogenesis of airway smooth muscle cells in asthma via STAT3 activation. Cell Cycle (Georgetown, TX). 2020;19(11):1275–84. 10.1080/15384101.2020.1746874
10. Liu W, Kong H, Zeng X, Wang J, Wang Z, Yan X, et al. Iptakalim inhibits PDGF-BB-induced human airway smooth muscle cells proliferation and migration. Exp Cell Res. 2015;336(2):204–10. 10.1016/j.yexcr.2015.06.020
11. Stamatiou R, Paraskeva E, Gourgoulianis K, Molyvdas PA, Hatziefthimiou A. Cytokines and growth factors promote airway smooth muscle cell proliferation. ISRN Inflamm. 2012;2012:731472. 10.5402/2012/731472
12. Karpova AY, Abe MK, Li J, Liu PT, Rhee JM, Kuo WL, et al. MEK1 is required for PDGF-induced ERK activation and DNA synthesis in tracheal myocytes. Am J Physiol. 1997;272(3, Pt 1):L558–65. 10.1152/ajplung.1997.272.3.L558
13. Krymskaya VP, Penn RB, Orsini MJ, Scott PH, Plevin RJ, Walker TR, et al. Phosphatidylinositol 3-kinase mediates mitogen-induced human airway smooth muscle cell proliferation. Am J Physiol. 1999;277(1):L65–78. 10.1152/ajplung.1999.277.1.L65
14. Zuyderduyn S, Sukkar MB, Fust A, Dhaliwal S, Burgess JK. Treating asthma means treating airway smooth muscle cells. Eur Respir J. 2008;32(2):265–74. 10.1183/09031936.00051407
15. Kwah JH, Peters AT. Asthma in adults: Principles of treatment. Allergy Asthma Proc. 2019;40(6):396–402. 10.2500/aap.2019.40.4256
16. Azman S, Sekar M, Bonam SR, Gan SH, Wahidin S, Lum PT, et al. Traditional medicinal plants conferring protection against ovalbumin-induced asthma in experimental animals: A review. J Asthma Allergy. 2021;14:641–62. 10.2147/JAA.S296391
17. Wei W, Rasul A, Sadiqa A, Sarfraz I, Hussain G, Nageen B, et al. Curcumol: From plant roots to cancer roots. Int J Biol Sci. 2019;15(8):1600–9. 10.7150/ijbs.34716
18. Mozzini Monteiro T, Ferrera Costa H, Carvalho Vieira G, Rodrigues Salgado PR, da Silva Stiebbe Salvadori MG, de Almeida RN, et al. Anti-asthmatic and anxiolytic effects of Herissantia tiubae, a Brazilian medicinal plant. Immun Inflamm Dis. 2016;4(2):201–12. 10.1002/iid3.107
19. Sim JH, Lee HS, Lee S, Park DE, Oh K, Hwang KA, et al. Anti-asthmatic activities of an ethanol extract of Aster yomena in an ovalbumin-induced murine asthma model. J Med Food. 2014;17(5):606–11. 10.1089/jmf.2013.2939
20. Yan D, Deng S, Gan W, Li S, Li Y. Curcumol attenuates epithelial-mesenchymal transition of nasopharyngeal carcinoma cells via TGF-β1. Mol Med Rep. 2018;17(6):7513–20. 10.3892/mmr.2018.8817
21. Huang LZ, Wang J, Lu FT, Yang FC, Chen X, Hong X, et al. Mechanism study on anti-proliferative effects of curcumol in human hepatocarcinoma HepG2 cells. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi. China J Chin Mater Med. 2013;38(11):1812–5.
22. Liu H, Wang J, Tao Y, Li X, Qin J, Bai Z, et al. Curcumol inhibits colorectal cancer proliferation by targeting miR-21 and modulated PTEN/PI3K/Akt pathways. Life Sci. 2019;221:354–61. 10.1016/j.lfs.2019.02.049
23. Tang QL, Guo JQ, Wang QY, Lin HS, Yang ZP, Peng T, et al. Curcumol induces apoptosis in SPC-A-1 human lung adenocarcinoma cells and displays anti-neoplastic effects in tumor bearing mice. Asian Pacific J Cancer Prev (APJCP). 2015;16(6):2307–12. 10.7314/APJCP.2015.16.6.2307
24. Jia Y, Gao L, Yang X, Zhang F, Chen A, Wang S, et al. Blockade of periostin-dependent migration and adhesion by curcumol via inhibition of nuclear factor kappa B signaling in hepatic stellate cells. Toxicology. 2020;440:152475. 10.1016/j.tox.2020.152475
25. Jia S, Guo P, Lu J, Huang X, Deng L, Jin Y, et al. Curcumol ameliorates lung inflammation and airway remodeling via inhibiting the abnormal activation of the Wnt/β-catenin pathway in chronic asthmatic mice. Drug Design Dev Ther. 2021;15:2641–51. 10.2147/DDDT.S292642
26. Hashem S, Nisar S, Sageena G, Macha MA, Yadav SK, Krishnankutty R, et al. Therapeutic effects of curcumol in several diseases; an overview. Nutr Cancer. 2021;73(2):181–95. 10.1080/01635581.2020.1749676
27. Lee JH, Johnson PR, Roth M, Hunt NH, Black JL. ERK activation and mitogenesis in human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2001;280(5):L1019–29. 10.1152/ajplung.2001.280.5.L1019
28. Deng Y, Zhang Y, Wu H, Shi Z, Sun X. Knockdown of FSTL1 inhibits PDGF-BB-induced human airway smooth muscle cell proliferation and migration. Mol Med Rep. 2017;15(6):3859–64. 10.3892/mmr.2017.6439
29. Li G, Jiang Q, Xu K. CREB family: A significant role in liver fibrosis. Biochimie. 2019;163:94–100. 10.1016/j.biochi.2019.05.014
30. Zirnask H, Pöllanen P, Suutre S, Kuuslahti M, Kotsar A, Pakarainen T, et al. Expression oF cAMP and creb in the human penis. J Men’s Health. 2019;15(4):12–7. 10.22374/jomh.v15i4.145
31. Crowley LC, Marfell BJ, Scott AP, Waterhouse NJ. Quantitation of apoptosis and necrosis by annexin V binding, propidium iodide uptake, and flow cytometry. Cold Spring Harb Protoc. 2016;2016(11). 10.1101/pdb.prot087288
32. Gallo-Oller G, Ordoñez R, Dotor J. A new background subtraction method for Western blot densitometry band quantification through image analysis software. J Immunol Methods. 2018;457:1–5. 10.1016/j.jim.2018.03.004
33. Pang X, Qiao J. Galectin-1 inhibits PDGF-BB-induced proliferation and migration of airway smooth muscle cells through the inactivation of PI3K/Akt signaling pathway. Biosci Rep. 2020;40(6): BSR20193899. 10.1042/BSR20193899
34. Dong Q, Jie Y, Ma J, Li C, Xin T, Yang D. Renal tubular cell death and inflammation response are regulated by the MAPK-ERK-CREB signaling pathway under hypoxia-reoxygenation injury. J recept Signal transduct Res. 2019;39(5–6):383–91. 10.1080/10799893.2019.1698050
35. Li R, Xin T, Li D, Wang C, Zhu H, Zhou H. Therapeutic effect of Sirtuin 3 on ameliorating nonalcoholic fatty liver disease: The role of the ERK-CREB pathway and Bnip3-mediated mitophagy. Redox Biol. 2018;18:229–43. 10.1016/j.redox.2018.07.011
36. Koga Y, Tsurumaki H, Aoki-Saito H, Sato M, Yatomi M, Takehara K, et al. Roles of cyclic AMP response element binding activation in the ERK1/2 and p38 MAPK signalling pathway in central nervous system, cardiovascular system, osteoclast differentiation and mucin and cytokine production. Int J Mol Sci. 2019;20(6):1346. 10.3390/ijms20061346