Login Register Cart 0
Generic placeholder image

Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

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

The Inefficiency of Low-concentration Curcumin Intervention in Ameliorating Chronic-stage Pulmonary Fibrosis

Author(s): Fathimath Muneesa Moideen and Yashodhar Prabhakar Bhandary*

Volume 20, Issue 2, 2024

Published on: 11 September, 2023

Article ID: e100823219619 Pages: 7

DOI: 10.2174/1573407219666230810094839

Price: $65

conference banner
Abstract

Background: Curcumin, a polyphenol compound, is reported to exhibit ameliorative effects in acute lung injury and different organ fibrosis models. We have previously demonstrated that curcumin, at a dose of 75 mg/kg, could modulate inflammatory mediators and fibrinolytic system proteins in the inflammatory stage as well as fibroproliferative stage in a mouse model of bleomycin (BLM) induced pulmonary fibrosis. In this study, we investigated the efficacy of the same dose of curcumin in resolving the established fibrotic stage in a mouse model of BLM-induced pulmonary fibrosis.

Methods: We prepared the fibrosis model by intranasal administration of BLM (2 mg/kg). Curcumin intervention was performed by intraperitoneal injection on 16th to 20th days post BLM exposure. The control group was administered with normal saline. The mice were sacrificed on the 21st day post BLM exposure.

Results: Histological analysis of the lung tissue samples indicated that curcumin (75 mg/kg) could not reverse the fibrotic features induced by BLM. We also performed RT-PCR and western blot to examine the molecular changes induced by BLM and curcumin. It was observed that curcumin could neither reduce the expressions of fibrotic markers nor restore the normal expressions of proteins in the fibrinolytic system.

Conclusion: Our data suggest that a low dose of curcumin is not effective in ameliorating the fibrotic stage of BLM-induced pulmonary fibrosis. An increased dose or a formulation that increases the bioavailability of curcumin could probably exhibit promising effects against pulmonary fibrosis in the future.

Keywords: Curcumin, pulmonary fibrosis, fibrinolytic system, bleomycin, acute lung injury, inflammatory mediators.

Graphical Abstract

[1]
Maher, T.M.; Bendstrup, E.; Dron, L.; Langley, J.; Smith, G.; Khalid, J.M.; Patel, H.; Kreuter, M. Global incidence and prevalence of idiopathic pulmonary fibrosis. Respir. Res., 2021, 22(1), 197.
[http://dx.doi.org/10.1186/s12931-021-01791-z] [PMID: 34233665]
[2]
Flaherty, K.R.; Wells, A.U.; Cottin, V.; Devaraj, A.; Walsh, S.L.F.; Inoue, Y.; Richeldi, L.; Kolb, M.; Tetzlaff, K.; Stowasser, S.; Coeck, C.; Clerisme-Beaty, E.; Rosenstock, B.; Quaresma, M.; Haeufel, T.; Goeldner, R.G.; Schlenker-Herceg, R.; Brown, K.K. Nintedanib in progressive fibrosing interstitial lung diseases. N. Engl. J. Med., 2019, 381(18), 1718-1727.
[http://dx.doi.org/10.1056/NEJMoa1908681] [PMID: 31566307]
[3]
Vancheri, C.; Kreuter, M.; Richeldi, L.; Ryerson, C.J.; Valeyre, D.; Grutters, J.C.; Wiebe, S.; Stansen, W.; Quaresma, M.; Stowasser, S.; Wuyts, W.A. Nintedanib with add-on pirfenidone in idiopathic pulmonary fibrosis. Results of the injourney trial. Am. J. Respir. Crit. Care Med., 2018, 197(3), 356-363.
[http://dx.doi.org/10.1164/rccm.201706-1301OC] [PMID: 28889759]
[4]
Kunnumakkara, A.B.; Bordoloi, D.; Padmavathi, G.; Monisha, J.; Roy, N.K.; Prasad, S.; Aggarwal, B.B. Curcumin, the golden nutraceutical: Multitargeting for multiple chronic diseases. Br. J. Pharmacol., 2017, 174(11), 1325-1348.
[http://dx.doi.org/10.1111/bph.13621] [PMID: 27638428]
[5]
Zhang, D.; Huang, C.; Yang, C.; Liu, R.J.; Wang, J.; Niu, J.; Brömme, D. Antifibrotic effects of curcumin are associated with overexpression of cathepsins K and L in bleomycin treated mice and human fibroblasts. Respir. Res., 2011, 12(1), 154.
[http://dx.doi.org/10.1186/1465-9921-12-154] [PMID: 22126332]
[6]
Saidi, A.; Kasabova, M.; Vanderlynden, L.; Wartenberg, M.; Kara-Ali, G.H.; Marc, D.; Lecaille, F.; Lalmanach, G. Curcumin inhibits the TGF-β1-dependent differentiation of lung fibroblasts via PPARγ-driven upregulation of cathepsins B and L. Sci. Rep., 2019, 9(1), 491.
[http://dx.doi.org/10.1038/s41598-018-36858-3] [PMID: 30679571]
[7]
Smith, M.R.; Gangireddy, S.R.; Narala, V.R.; Hogaboam, C.M.; Standiford, T.J.; Christensen, P.J.; Kondapi, A.K.; Reddy, R.C. Curcumin inhibits fibrosis-related effects in IPF fibroblasts and in mice following bleomycin-induced lung injury. Am. J. Physiol. Lung Cell. Mol. Physiol., 2010, 298(5), L616-L625.
[http://dx.doi.org/10.1152/ajplung.00002.2009] [PMID: 20061443]
[8]
Fathimath Muneesa, M.; Barki, R.R.; Shaikh, S.B.; Bhandary, Y.P. Curcumin intervention during progressive fibrosis controls inflammatory cytokines and the fibrinolytic system in pulmonary fibrosis. Toxicol. Appl. Pharmacol., 2022, 449, 116116.
[http://dx.doi.org/10.1016/j.taap.2022.116116] [PMID: 35716765]
[9]
Marton, L.T.; Pescinini-E-Salzedas, L.M.; Côrtes Camargo, M.E.; Barbalho, S.M.; Santos Haber, J.F.D.; Vargas Sinatora, R.; Penteado Detregiachi, C.R.; S Girio, R.J.; Vieira Buchaim, D.; Dos Santos Bueno, P.C. The effects of curcumin on diabetes mellitus: A systematic review. Front Endocrinol., 2021, 12, 669448.
[http://dx.doi.org/10.3389/fendo.2021.669448] [PMID: 34012421]
[10]
Hashemi, M.; Mirzaei, S.; Barati, M.; Hejazi, E.S.; Kakavand, A.; Entezari, M.; Salimimoghadam, S.; Kalbasi, A.; Rashidi, M.; Taheriazam, A.; Sethi, G. Curcumin in the treatment of urological cancers: Therapeutic targets, challenges and prospects. Life Sci., 2022, 309, 120984.
[http://dx.doi.org/10.1016/j.lfs.2022.120984] [PMID: 36150461]
[11]
Benameur, T.; Soleti, R.; Panaro, M.A.; La Torre, M.E.; Monda, V.; Messina, G.; Porro, C. Curcumin as prospective anti-aging natural compound: Focus on brain. Molecules, 2021, 26(16), 4794.
[http://dx.doi.org/10.3390/molecules26164794] [PMID: 34443381]
[12]
Mouratis, M.A.; Aidinis, V. Modeling pulmonary fibrosis with bleomycin. Curr. Opin. Pulm. Med., 2011, 17(5), 355-361.
[http://dx.doi.org/10.1097/MCP.0b013e328349ac2b] [PMID: 21832918]
[13]
Izbicki, G.; Segel, M.J.; Christensen, T.G.; Conner, M.W.; Breuer, R. Time course of bleomycin-induced lung fibrosis. Int. J. Exp. Pathol., 2002, 83(3), 111-119.
[http://dx.doi.org/10.1046/j.1365-2613.2002.00220.x] [PMID: 12383190]
[14]
Moeller, A.; Ask, K.; Warburton, D.; Gauldie, J.; Kolb, M. The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis? Int. J. Biochem. Cell Biol., 2008, 40(3), 362-382.
[http://dx.doi.org/10.1016/j.biocel.2007.08.011] [PMID: 17936056]
[15]
Gouda, M.M.; Prabhu, A.; Bhandary, Y.P. Curcumin alleviates IL‐17A‐mediated p53‐PAI‐1 expression in bleomycin‐induced alveolar basal epithelial cells. J. Cell. Biochem., 2018, 119(2), 2222-2230.
[http://dx.doi.org/10.1002/jcb.26384] [PMID: 28902433]
[16]
Gouda, M.M.; Bhandary, Y.P. Curcumin down‐regulates IL‐17A mediated p53‐fibrinolytic system in bleomycin induced acute lung injury in vivo. J. Cell. Biochem., 2018, 119(9), 7285-7299.
[http://dx.doi.org/10.1002/jcb.27026] [PMID: 29775223]
[17]
Hu, Y.; Li, M.; Zhang, M.; Jin, Y. Inhalation treatment of idiopathic pulmonary fibrosis with curcumin large porous microparticles. Int. J. Pharm., 2018, 551(1-2), 212-222.
[http://dx.doi.org/10.1016/j.ijpharm.2018.09.031] [PMID: 30227240]
[18]
Chai, Y.; Chen, Y.; Lin, S.; Xie, K.; Wang, C.; Yang, Y.; Xu, F. Curcumin regulates the differentiation of naïve CD4+T cells and activates IL-10 immune modulation against acute lung injury in mice. Biomed. Pharmacother., 2020, 125, 109946.
[http://dx.doi.org/10.1016/j.biopha.2020.109946] [PMID: 32004976]
[19]
Chauhan, P.S.; Dash, D.; Singh, R. Intranasal curcumin inhibits pulmonary fibrosis by Modulating Matrix Metalloproteinase-9 (MMP-9) in ovalbumin-induced chronic asthma. Inflammation, 2017, 40(1), 248-258.
[http://dx.doi.org/10.1007/s10753-016-0475-3] [PMID: 27866296]
[20]
Ma, J.; Ma, S.; Ding, C. Curcumin reduces cardiac fibrosis by inhibiting myofibroblast differentiation and decreasing transforming growth factor β1 and matrix metalloproteinase 9 / tissue inhibitor of metalloproteinase 1. Chin. J. Integr. Med., 2017, 23(5), 362-369.
[http://dx.doi.org/10.1007/s11655-015-2159-5] [PMID: 26956464]
[21]
Gouda, M.M.; Prabhu, A.; Bhandary, Y.P. IL-17A suppresses and curcumin up-regulates Akt expression upon bleomycin exposure. Mol. Biol. Rep., 2018, 45(4), 645-650.
[http://dx.doi.org/10.1007/s11033-018-4199-3] [PMID: 29808357]
[22]
Shaikh, S.B.; Prabhu, A.; Bhandary, Y.P. Curcumin targets p53-fibrinolytic system in TGF-β1 mediated alveolar epithelial mesenchymal transition in alveolar epithelial cells. Endocr. Metab. Immune Disord. Drug Targets, 2020, 21(8), 1441-1452.
[PMID: 32990549]
[23]
Shaikh, S.B.; Prabhakar Bhandary, Y. Effect of curcumin on IL-17A mediated pulmonary AMPK kinase/cyclooxygenase-2 expressions via activation of NFκB in bleomycin-induced acute lung injury in vivo. Int. Immunopharmacol., 2020, 85, 106676.
[http://dx.doi.org/10.1016/j.intimp.2020.106676] [PMID: 32535538]

Rights & Permissions Print Cite
Article Metrics
13
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy