Home > Journals > SCIREA Journal of Clinical Medicine > Archive > Paper Information

Protective Mechanisms of Quercetin in Various Lung-induced Injuries

Volume 7, Issue 3, June 2022    |    PP. 206-223    |PDF (567 K)|    Pub. Date: June 4, 2022
DOI: 10.54647/cm32844    13 Downloads     237 Views  

Wahyu Choirur Rizky, Sulaiman Al Rajhi Colleges, Saudi Arabia
Muhammad Candragupta Jihwaprani, Sulaiman Al Rajhi Colleges, Saudi Arabia
Mazhar Mushtaq, Sulaiman Al Rajhi Colleges, Saudi Arabia

Acute respiratory distress syndrome (ARDS) remains to be a paramount healthcare issue, frequently resulting in respiratory failure and death. Recently, the rapidly expanding knowledge about the pathophysiology of novel severe acute respiratory syndrome (nSARS-CoV-2) infection provides a significant insight regarding the implication of cytokines storm, which mainly causes an acute lung injury (ALI) in COVID-19 patients and directs the disease severity. As hypoxemia worsens, ALI can progress into ARDS leading to a high mortality rate. Despite advances in clinical care, the lungs of a subset of ARDS survivors show persistent fibrotic changes triggered by an imbalance between higher reactive oxidative species and lower anti-oxidative substrates. Clinical evidence have shown the pneumoprotective effects of quercetin in certain pulmonary conditions. Albeit many studies evaluating quercetin's anti-inflammatory action on bacterial lipopolysaccharide-induced models have been done, anti-inflammatory studies using viral-induced models or its surrogate are still lacking. In this review, the authors discuss the possible molecular mechanism of quercetin in targeting specific pathways in lung injury and its sequelae, including pulmonary fibrosis that is induced both by infectious and pneumotoxic agents.

Quercetin, acute lung injury, acute respiratory distress syndrome, anti-inflammatory, pulmonary fibrosis, pneumoprotective

Cite this paper
Wahyu Choirur Rizky, Muhammad Candragupta Jihwaprani, Mazhar Mushtaq, Protective Mechanisms of Quercetin in Various Lung-induced Injuries, SCIREA Journal of Clinical Medicine. Vol. 7 , No. 3 , 2022 , pp. 206 - 223 . https://doi.org/10.54647/cm32844


[ 1 ] Burnham EL, Janssen WJ, Riches DWH, Moss M, Downey GP. The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance. Eur Respir J. 2014;43:276-285. doi: 10.1183/09031936.00196412.
[ 2 ] Zhang J, Huang X, Ding D, et al. Comparative study of acute lung injury in COVID-19 and non-COVID-19 patients. Front Med. 2021;8. doi: 10.3389/fmed.2021.666629.
[ 3 ] Takashima K, Matsushima M, Hashimoto K, et al. Protective effects of intratracheally administered quercetin on lipopolysaccharide-induced acute lung injury. Respir Res. 2014;15(1):1-10. doi: 10.1186/s12931-014-0150-x.
[ 4 ] Huang R, Zhong T, Wu H. Experimental research Quercetin protects against lipopolysaccharide-induced acute lung injury in rats through suppression of inflammation and oxidative stress. Arch Med Sci. 2015;11(2):427-432. doi: 10.5114/aoms.2015.50975.
[ 5 ] Wang X, Li Y, qiang Hu Z, et al. Protective effect of quercetin in LPS-induced murine acute lung injury mediated by cAMP-Epac pathway. Inflammation. 2018;41(3):1093-1103. doi: 10.1007/s10753-018-0761-3.
[ 6 ] Cui W, Hu G, Peng J, Mu L, Liu J, Qiao L. Quercetin exerted protective effects in a rat model of sepsis via inhibition of reactive oxygen species (ROS) and downregulation of high mobility group box 1 (HMGB1) protein expression. Med Sci Monit Int Med J Exp Clin Res. 2019;25:5795. doi: 10.12659/MSM.916044.
[ 7 ] Verma R, Kushwah L, Gohel D, Patel M, Marvania T, Balakrishnan S. Evaluating the ameliorative potential of quercetin against the bleomycin-induced pulmonary fibrosis in Wistar rats. Pulm Med. 2013;2013. doi: 10.1155/2013/921724.
[ 8 ] Veith C, Drent M, Bast A, van Schooten FJ, Boots AW. The disturbed redox-balance in pulmonary fibrosis is modulated by the plant flavonoid quercetin. Toxicol Appl Pharmacol. 2017;336:40-48. doi: 10.1016/j.taap.2017.10.001.
[ 9 ] Rizky WC, Jihwaprani MC, Kindi AA, Ansori ANM, Mushtaq M. The pharmacological mechanism of quercetin as adjuvant therapy of COVID-19. Life Res. 2022;5(3):3. doi: 10.53388/2022-0205-302
[ 10 ] Kosyreva A, Dzhalilova D, Lokhonina A, Vishnyakova P, Fatkhudinov T. The role of macrophages in the pathogenesis of SARS-CoV-2-associated acute respiratory distress syndrome. Front Immunol. 2021;12:1667. doi: 10.3389/fimmu.2021.682871
[ 11 ] Tremblay LN, Slutsky AS. Ventilator-induced lung injury: from the bench to the bedside. Appl Physiol intensive care Med. 2006:357-366. doi: 10.1007/s00134-005-2817-8
[ 12 ] Parikh SM, Mammoto T, Schultz A, et al. Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in sepsis in humans. PLoS Med. 2006;3(3):e46.doi: 10.1371/journal.pmed.0030046
[ 13 ] Craig TR, Duffy MJ, Shyamsundar M, et al. Extravascular lung water indexed to predicted body weight is a novel predictor of intensive care unit mortality in patients with acute lung injury. Crit Care Med. 2010;38(1):114-120. doi: 10.1097/CCM.0b013e3181b43050.
[ 14 ] O’Sullivan S, Medina C, Ledwidge M, Radomski MW, Gilmer JF. Nitric oxide-matrix metaloproteinase-9 interactions: biological and pharmacological significance: NO and MMP-9 interactions. Biochim Biophys Acta (BBA)-Molecular Cell Res. 2014;1843(3):603-617. doi: 10.1016/j.bbamcr.2013.12.006.
[ 15 ] Guo Y, Ma L, Zhang F, Sun R, Li T. Neutrophil elastase ameliorates matrix metalloproteinase-9 to promote lipopolysaccharide-induced acute lung injury in mice1. Acta Cir Bras. 2016;31:382-388. doi: 10.1590/S0102-865020160060000004.
[ 16 ] Zhao S, Chen F, Yin Q, Wang D, Han W, Zhang Y. Reactive oxygen species interact with NLRP3 inflammasomes and are involved in the inflammation of sepsis: from mechanism to treatment of progression. Front Physiol. 2020;11. doi: 10.3389/fphys.2020.571810.
[ 17 ] Stevens NE, Chapman MJ, Fraser CK, Kuchel TR, Hayball JD, Diener KR. Therapeutic targeting of HMGB1 during experimental sepsis modulates the inflammatory cytokine profile to one associated with improved clinical outcomes. Sci Rep. 2017;7(1):1-14. doi: 10.1038/s41598-017-06205-z.
[ 18 ] Wang L, Chen J, Wang B, et al. Protective effect of quercetin on lipopolysaccharide-induced acute lung injury in mice by inhibiting inflammatory cell influx. Exp Biol Med. 2014;239(12):1653-1662. doi: 10.1177/1535370214537743.
[ 19 ] Chi G, Zhong W, Liu Y, et al. Isorhamnetin protects mice from lipopolysaccharide-induced acute lung injury via the inhibition of inflammatory responses. Inflamm Res. 2016;65(1):33-41. doi: 10.1007/s00011-015-0887-9.
[ 20 ] Kim Y, Park W. Anti‐inflammatory effect of quercetin on RAW 264.7 mouse macrophages induced with polyinosinic‐polycytidylic acid. Molecules. 2016;21(4):450. doi: 10.3390/molecules21040450.
[ 21 ] Timmins JM, Ozcan L, Seimon TA, et al. Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways. J Clin Invest. 2009;119(10):2925-2941. doi: 10.1172/JCI38857.
[ 22 ] Alzohairy MA, Khan AA, Ansari MA, et al. Protective Effect of Quercetin, a Flavonol against Benzo(a)pyrene-Induced Lung Injury via Inflammation, Oxidative Stress, Angiogenesis and Cyclooxygenase-2 Signalling Molecule. Appl Sci. 2021;11(18). doi:10.3390/app11188675
[ 23 ] Chan S-T, Chuang C-H, Yeh C-L, et al. Quercetin supplementation suppresses the secretion of pro-inflammatory cytokines in the lungs of Mongolian gerbils and in A549 cells exposed to benzo [a] pyrene alone or in combination with β-carotene: in vivo and ex vivo studies. J Nutr Biochem. 2012;23(2):179-185. doi: 10.1016/j.jnutbio.2010.11.014.
[ 24 ] Fredenburgh LE, Perrella MA, Mitsialis SA. The role of heme oxygenase-1 in pulmonary disease. Am J Respir Cell Mol Biol. 2007;36(2):158-165. doi: 10.1165/rcmb.2006-0331TR.
[ 25 ] Nakamura T, Matsushima M, Hayashi Y, et al. Attenuation of transforming growth factor–β–stimulated collagen production in fibroblasts by quercetin-induced Heme oxygenase–1. Am J Respir Cell Mol Biol. 2011;44(5):614-620. doi: 10.1165/rcmb.2010-0338OC
[ 26 ] Hayashi Y, Matsushima M, Nakamura T, et al. Quercetin protects against pulmonary oxidant stress via heme oxygenase-1 induction in lung epithelial cells. Biochem Biophys Res Commun. 2012;417(1):169-174. doi: 10.1016/j.bbrc.2011.11.078.
[ 27 ] Tanigawa S, Fujii M, Hou D-X. Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin. Free Radic Biol Med. 2007;42(11):1690-1703. doi: 10.1016/j.freeradbiomed.2007.02.017.
[ 28 ] Schafer M, White T, Iijima K, et al. CELLULAR SENESCENCE DRIVES FIBROTIC PULMONARY DISEASE. Innov Aging. 2017;1(Suppl 1):135. doi: 10.1038/ncomms14532
[ 29 ] Lehmann M, Korfei M, Mutze K, et al. Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo. Eur Respir J. 2017;50(2). doi: 10.1183/13993003.02367-2016
[ 30 ] Hohmann MS, Habiel DM, Coelho AL, Verri Jr WA, Hogaboam CM. Quercetin enhances ligand-induced apoptosis in senescent idiopathic pulmonary fibrosis fibroblasts and reduces lung fibrosis in vivo. Am J Respir Cell Mol Biol. 2019;60(1):28-40. doi: 10.1165/rcmb.2017-0289OC
[ 31 ] Meng L, Lv Z, Yu ZZ, Xu D, Yan X. Protective effect of quercetin on acute lung injury in rats with sepsis and its influence on ICAM-1 and MIP-2 expression. Genet Mol Res. 2016;15(3). doi: 10.4238/gmr.15037265.
[ 32 ] Zhong H, Lin H, Pang Q, et al. Macrophage ICAM-1 functions as a regulator of phagocytosis in LPS induced endotoxemia. Inflamm Res. 2021;70(2):193-203. doi: 10.1007/s00011-021-01437-2
[ 33 ] Chaochao Q, Lou G, Yang Y, et al. Macrophage inflammatory Protein-2 in high mobility group box 1 secretion of macrophage cells exposed to Lipopolysaccharide. Cell Physiol Biochem. 2017;42(3):913-928. doi: 10.1159/000478646
[ 34 ] Ying B, Yang T, Song X, et al. Quercetin inhibits IL-1 beta-induced ICAM-1 expression in pulmonary epithelial cell line A549 through the MAPK pathways. Mol Biol Rep. 2009;36(7):1825-1832. doi: 10.1007/s11033-008-9386-1.
[ 35 ] Chen F, Bower J, Demers L, Shi X. Upstream signal transduction of NF-kB activation. Atlas Genet Cytogenet Oncol Haematol. 2011;6(2):156-170. doi: 10.4267/2042/37857
[ 36 ] Tripathi A, Kumar B, Sagi Id SSK. Prophylactic efficacy of Quercetin in ameliorating the hypoxia induced vascular leakage in lungs of rats. 2019. doi: 10.1371/journal.pone.0219075

Submit A Manuscript
Review Manuscripts
Join As An Editorial Member
Most Views
by Sergey M. Afonin
3057 Downloads 59577 Views
by Jian-Qiang Wang, Chen-Xi Wang, Jian-Guo Wang, HRSCNP Research Team
15 Downloads 45052 Views
by Syed Adil Hussain, Taha Hasan Associate Professor
2418 Downloads 24076 Views
by Omprakash Sikhwal, Yashwant Vyas
2486 Downloads 20230 Views
by Munmun Nath, Bijan Nath, Santanu Roy
2364 Downloads 19950 Views
Upcoming Conferences