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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

General Research Article

In vitro and Molecular Docking Analysis of Quercetin as an Anti-inflammatory and Antioxidant

Author(s): Alireza Bastin, Maryam Teimouri, Sanaz Faramarz, Maryam Shabani, Amir Hossein Doustimotlagh and Asie Sadeghi*

Volume 29, Issue 11, 2023

Published on: 11 April, 2023

Page: [883 - 891] Pages: 9

DOI: 10.2174/1381612829666230330084043

Price: $65

Abstract

Introduction: Quercetin (3,3′,4′,5,7-pentahydroxyflavone) is a dietary flavonoid with good antioxidant and anti-inflammatory properties.

Aims: The present study aims to determine these effects in peripheral blood mononuclear cells (PBMCs) evoked by lipopolysaccharides (LPS).

Methods: The mRNA expression and protein secretion of inflammatory mediators were evaluated by enzyme- linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (PCR), respectively. Western blotting was utilized for assessing p65-NF-κB phosphorylation. Ransod kits evaluated the glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity in the cell lysates. Ultimately, the molecular docking approach was performed to investigate the biological activity of Quercetin against NF-κB pathway proteins and antioxidant enzymes.

Results: The findings revealed that quercetin significantly attenuated the expression and secretion of inflammatory mediators and p65-NF-κB phosphorylation in LPS-induced PBMCs. Additionally, quercetin dose-dependently improved the activities of SOD and GPx enzymes and decreased LPS-mediated oxidative stress in PBMCs. Moreover, quercetin has a considerable binding affinity to IκKb, the core element of the NF-κB pathway and the antioxidant enzyme SOD.

Conclusion: The data show that quercetin plays a vital role in ameliorating inflammation and oxidative stress caused by LPS in PBMCs.

« Previous
[1]
Hussain T, Tan B, Yin Y, Blachier F, Tossou MC, Rahu N. Oxidative stress and inflammation: What polyphenols can do for us? Oxid Med Cell Longev 2016; 2016.
[http://dx.doi.org/10.1155/2016/7432797]
[2]
Rastogi S, Haldar C. Comparative effect of melatonin and quercetin in counteracting LPS induced oxidative stress in bone marrow mononuclear cells and spleen of Funambulus pennanti. Food Chem Toxicol 2018; 120: 243-52.
[http://dx.doi.org/10.1016/j.fct.2018.06.062] [PMID: 29964085]
[3]
Biswas SK. Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox? Oxid Med Cell Longev 2016; 2016: 5698931.
[http://dx.doi.org/10.1155/2016/5698931]
[4]
Hsueh YJ, Chen YN, Tsao YT, Cheng CM, Wu WC, Chen HC. The pathomechanism, antioxidant biomarkers, and treatment of oxidative stress-related eye diseases. Int J Mol Sci 2022; 23(3): 1255.
[http://dx.doi.org/10.3390/ijms23031255] [PMID: 35163178]
[5]
Liguori I, Russo G, Curcio F, et al. Oxidative stress, aging, and diseases. Clin Interv Aging 2018; 13: 757-72.
[http://dx.doi.org/10.2147/CIA.S158513] [PMID: 29731617]
[6]
Karak P. Biological activities of flavonoids: An overview. Int J Pharm Sci Res 2019; 10: 1567-74.
[7]
Panche AN, Diwan AD, Chandra SR. Flavonoids: An overview. J Nutr Sci 2016; 5: e47.
[http://dx.doi.org/10.1017/jns.2016.41] [PMID: 28620474]
[8]
Bastin A, Sadeghi A, Nematollahi MH, Abolhassani M, Mohammadi A, Akbari H. The effects of malvidin on oxidative stress parameters and inflammatory cytokines in LPS-induced human THP-1 cells. J Cell Physiol 2021; 236(4): 2790-9.
[http://dx.doi.org/10.1002/jcp.30049] [PMID: 32914418]
[9]
Lee HN, Shin SA, Choo GS, et al. Anti-inflammatory effect of quercetin and galangin in LPS-stimulated RAW264.7 macrophages and DNCB-induced atopic dermatitis animal models. Int J Mol Med 2018; 41(2): 888-98.
[PMID: 29207037]
[10]
Ginwala R, Bhavsar R, Chigbu DI, Jain P, Khan ZK. Potential role of flavonoids in treating chronic inflammatory diseases with a special focus on the anti-inflammatory activity of apigenin. Antioxidants 2019; 8(2): 35.
[http://dx.doi.org/10.3390/antiox8020035] [PMID: 30764536]
[11]
Parasuraman S, Anand David AV, Arulmoli R. Overviews of biological importance of quercetin: A bioactive flavonoid. Pharmacogn Rev 2016; 10(20): 84-9.
[http://dx.doi.org/10.4103/0973-7847.194044] [PMID: 28082789]
[12]
Long Y, Wang G, Li K, et al. Oxidative stress and NF-κB signaling are involved in LPS induced pulmonary dysplasia in chick embryos. Cell Cycle 2018; 17(14): 1757-71.
[http://dx.doi.org/10.1080/15384101.2018.1496743] [PMID: 30010471]
[13]
Sakai J, Cammarota E, Wright JA, et al. Lipopolysaccharide-induced NF-κB nuclear translocation is primarily dependent on MyD88, but TNFα expression requires TRIF and MyD88. Sci Rep 2017; 7(1): 1428-8.
[http://dx.doi.org/10.1038/s41598-017-01600-y] [PMID: 28469251]
[14]
Liu H, Hao J, Wu C, et al. Eupatilin alleviates lipopolysaccharide-induced acute lung injury by inhibiting inflammation and oxidative stress. Med Sci Monit 2019; 25: 8289-96.
[http://dx.doi.org/10.12659/MSM.917406] [PMID: 31680664]
[15]
Remko M. Theoretical study of molecular structure, pKa, lipophilicity, solubility, absorption, and polar surface area of some hypoglycemic agents. J Mol Struct Theochem 2009; 897(1-3): 73-82.
[http://dx.doi.org/10.1016/j.theochem.2008.11.021]
[16]
De Benedetti PG, Quartieri S, Rastelli A. A theoretical study of the structure-activity relationship in sulpha drugs. J Mol Struct Theochem 1981; 85(1-2): 45-51.
[http://dx.doi.org/10.1016/0166-1280(81)85048-8]
[17]
Luzhkov VB. Electronic parameters and molecular mechanisms of biological action of nitroxyl radicals. J Mol Struct Theochem 1985; 121: 165-72.
[http://dx.doi.org/10.1016/0166-1280(85)80056-7]
[18]
Poustforoosh A, Hashemipour H, Pardakhty A, Pour MK. Preparation of nano-micelles of meloxicam for transdermal drug delivery and simulation of drug release: A computational supported experimental study. Can J Chem Eng 2022; 100(11): 3428-36.
[http://dx.doi.org/10.1002/cjce.24339]
[19]
Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010; 31(2): 455-61.
[PMID: 19499576]
[20]
Bultinck P, De Winter H, Langenaeker W, Tollenare JP. Computational medicinal chemistry for drug discovery. Boca Raton, Florida, US: CRC Press 2003.
[http://dx.doi.org/10.1201/9780203913390]
[21]
Sadeghi A, Rostamirad A, Seyyedebrahimi S, Meshkani R. Curcumin ameliorates palmitate-induced inflammation in skeletal muscle cells by regulating JNK/NF-kB pathway and ROS production. Inflammopharmacology 2018; 26(5): 1265-72.
[http://dx.doi.org/10.1007/s10787-018-0466-0] [PMID: 29644554]
[22]
Sadeghi A, Shabani M, Alizadeh S, Meshkani R. Interplay between oxidative stress and autophagy function and its role in inflammatory cytokine expression induced by palmitate in skeletal muscle cells. Cytokine 2020; 125: 154835.
[http://dx.doi.org/10.1016/j.cyto.2019.154835] [PMID: 31479873]
[23]
Bastin AR, Nazari-Robati M, Sadeghi H, Doustimotlagh AH, Sadeghi A. Trehalose and N-acetyl cysteine alleviate inflammatory cytokine production and oxidative stress in LPS-stimulated human peripheral blood mononuclear cells. Immunol Invest 2022; 51(4): 963-79.
[http://dx.doi.org/10.1080/08820139.2021.1891095] [PMID: 33632046]
[24]
Bastin AR, Sadeghi A, Abolhassani M, Doustimotlagh AH, Mohammadi A. Malvidin prevents lipopolysaccharide-induced oxidative stress and inflammation in human peripheral blood mononuclear cells. IUBMB Life 2020; 72(7): 1504-14.
[http://dx.doi.org/10.1002/iub.2286] [PMID: 32268009]
[25]
Sadeghi A, Bastin AR, Ghahremani H, Doustimotlagh AH. The effects of rosmarinic acid on oxidative stress parameters and inflammatory cytokines in lipopolysaccharide-induced peripheral blood mononuclear cells. Mol Biol Rep 2020; 47(5): 3557-66.
[http://dx.doi.org/10.1007/s11033-020-05447-x] [PMID: 32350743]
[26]
Poustforoosh A, Hashemipour H, Tüzün B, Pardakhty A, Mehrabani M, Nematollahi MH. Evaluation of potential anti-RNA-dependent RNA polymerase (RdRP) drugs against the newly emerged model of COVID-19 RdRP using computational methods. Biophys Chem 2021; 272: 106564.
[http://dx.doi.org/10.1016/j.bpc.2021.106564] [PMID: 33711743]
[27]
Poustforoosh A, Faramarz S, Nematollahi MH, et al. 3D-QSAR, molecular docking, molecular dynamics, and ADME/T analysis of marketed and newly designed flavonoids as inhibitors of Bcl-2 family proteins for targeting U-87 glioblastoma. J Cell Biochem 2022; 123(2): 390-405.
[http://dx.doi.org/10.1002/jcb.30178] [PMID: 34791695]
[28]
Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: How are they linked? Free Radic Biol Med 2010; 49(11): 1603-16.
[http://dx.doi.org/10.1016/j.freeradbiomed.2010.09.006] [PMID: 20840865]
[29]
Biswas S, Das R, Ray Banerjee E. Role of free radicals in human inflammatory diseases. AIMS Biophys 2017; 4(4): 596-614.
[http://dx.doi.org/10.3934/biophy.2017.4.596]
[30]
Reynés B, Díaz-Rúa R, Cifre M, Oliver P, Palou A. Peripheral blood mononuclear cells as a potential source of biomarkers to test the efficacy of weight-loss strategies. Obesity 2015; 23(1): 28-31.
[http://dx.doi.org/10.1002/oby.20918] [PMID: 25294800]
[31]
Cifre M, Díaz-Rúa R, Varela-Calviño R, et al. Human peripheral blood mononuclear cell in vitro system to test the efficacy of food bioactive compounds: Effects of polyunsaturated fatty acids and their relation with BMI. Mol Nutr Food Res 2017; 61(4): 1600353.
[http://dx.doi.org/10.1002/mnfr.201600353] [PMID: 27873461]
[32]
Busquets-Cortés C, Capó X, Bibiloni M, et al. Peripheral blood mononuclear cells antioxidant adaptations to regular physical activity in elderly people. Nutrients 2018; 10(10): 1555.
[http://dx.doi.org/10.3390/nu10101555] [PMID: 30347790]
[33]
Liao YR, Lin JY. Quercetin intraperitoneal administration ameliorates lipopolysaccharide-induced systemic inflammation in mice. Life Sci 2015; 137: 89-97.
[http://dx.doi.org/10.1016/j.lfs.2015.07.015] [PMID: 26209141]
[34]
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; 2(2): 427-32.
[http://dx.doi.org/10.5114/aoms.2015.50975] [PMID: 25995762]
[35]
Khan A, Ali T, Rehman SU, et al. Neuroprotective effect of quercetin against the detrimental effects of LPS in the adult mouse brain. Front Pharmacol 2018; 9: 1383-3.
[http://dx.doi.org/10.3389/fphar.2018.01383] [PMID: 30618732]
[36]
Rasmi Y, Bagheri M, Faramarz-Gaznagh S, et al. Transcriptional activity of tumor necrosis factor-alpha gene in peripheral blood mononuclear cells in patients with coronary slow flow. ARYA Atheroscler 2017; 13(4): 196-201.
[PMID: 29147131]
[37]
Kany S, Vollrath JT, Relja B. Cytokines in inflammatory disease. Int J Mol Sci 2019; 20(23): 6008.
[http://dx.doi.org/10.3390/ijms20236008] [PMID: 31795299]
[38]
Takashima K, Matsushima M, Hashimoto K, et al. Protective effects of intratracheally administered Quercetin on lipopoly- saccharide-induced acute lung injury. Respir Res 2014; 15(1): 150.
[http://dx.doi.org/10.1186/s12931-014-0150-x] [PMID: 25413579]
[39]
Peng Z, Gong X, Yang Y, et al. Hepatoprotective effect of Quercetin against LPS/ d -GalN induced acute liver injury in mice by inhibiting the IKK/NF-κB and MAPK signal pathways. Int Immunopharmacol 2017; 52: 281-9.
[http://dx.doi.org/10.1016/j.intimp.2017.09.022] [PMID: 28963941]
[40]
Xiong G, Ji W, Wang F, et al. Quercetin inhibits inflammatory response induced by LPS from Porphyromonas gingivalis in human gingival fibroblasts via suppressing NF-κB signaling pathway. Biomed Res Int 2019; 2019: 6282635.
[41]
Xue F, Nie X, Shi J, et al. Quercetin inhibits LPS-induced inflammation and ox-LDL-induced lipid deposition. Front Pharmacol 2017; 8: 40.
[http://dx.doi.org/10.3389/fphar.2017.00040] [PMID: 28217098]
[42]
Giridharan S, Srinivasan M. Mechanisms of NF-κB p65 and strategies for therapeutic manipulation. J Inflamm Res 2018; 11: 407-19.
[http://dx.doi.org/10.2147/JIR.S140188] [PMID: 30464573]
[43]
Bahar E, Kim JY, Yoon H. Quercetin attenuates manganese-induced neuroinflammation by alleviating oxidative stress through regulation of apoptosis, iNOS/NF-κB and HO-1/Nrf2 pathways. Int J Mol Sci 2017; 18(9): 1989.
[http://dx.doi.org/10.3390/ijms18091989] [PMID: 28914791]
[44]
Cheng S-C, Huang W-C, S Pang JH, Wu YH, Cheng CY. Quercetin inhibits the production of IL-1β-induced inflammatory cytokines and chemokines in ARPE-19 cells via the MAPK and NF-κB signaling pathways. Int J Mol Sci 2019; 20(12): 2957.
[http://dx.doi.org/10.3390/ijms20122957] [PMID: 31212975]
[45]
Chen H, Lu C, Liu H, et al. Quercetin ameliorates imiquimod-induced psoriasis-like skin inflammation in mice via the NF-κB pathway. Int Immunopharmacol 2017; 48: 110-7.
[http://dx.doi.org/10.1016/j.intimp.2017.04.022] [PMID: 28499194]
[46]
Gao C, Liu Y, Jiang C, et al. Intensive running enhances NF-κB activity in the mice liver and the intervention effects of Quercetin. Nutrients 2020; 12(9): 2770.
[http://dx.doi.org/10.3390/nu12092770] [PMID: 32932805]
[47]
Wang X, Yu Z, Wang C, et al. Alantolactone, a natural sesquiterpene lactone, has potent antitumor activity against glioblastoma by targeting IKKβ kinase activity and interrupting NF-κB/COX-2- mediated signaling cascades. J Exp Clin Cancer Res 2017; 36(1): 93.
[http://dx.doi.org/10.1186/s13046-017-0563-8]
[48]
Yu Z, Guo W, Ma X, et al. Gamabufotalin, a bufadienolide compound from toad venom, suppresses COX-2 expression through targeting IKKβ/NF-κB signaling pathway in lung cancer cells. Mol Cancer 2014; 13(1): 203.
[http://dx.doi.org/10.1186/1476-4598-13-203]
[49]
Shah SA, Khan M, Jo MH, Jo MG, Amin FU, Kim MO. Melatonin stimulates the SIRT 1/Nrf2 signaling pathway counteracting lipopolysaccharide (LPS)-induced oxidative stress to rescue postnatal rat brain. CNS Neurosci Ther 2017; 23(1): 33-44.
[http://dx.doi.org/10.1111/cns.12588] [PMID: 27421686]
[50]
Xu X, Li H, Hou X, et al. Punicalagin induces Nrf2/HO-1 expression via upregulation of PI3K/AKT pathway and inhibits LPS-induced oxidative stress in RAW264. 7 macrophages. Mediators Inflamm 2015; 2015: 380218.
[51]
Lee YL, Park S, Chen BH, et al. Pretreated quercetin protects gerbil hippocampal CA1 pyramidal neurons from transient cerebral ischemic injury by increasing the expression of antioxidant enzymes. Neural Regen Res 2017; 12(2): 220-7.
[http://dx.doi.org/10.4103/1673-5374.200805] [PMID: 28400803]
[52]
Akkoyun DC, Akyuz A, Dogan M, et al. Quercetin inhibits heart injury in lipopolysaccharide-induced endotoxemic model by suppressing the effects of reactive oxygen species. Anal Quant Cytopathol Histpathol 2016; 38: 183-8.
[53]
Lubos E, Loscalzo J, Handy DE. Glutathione peroxidase-1 in health and disease: From molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal 2011; 15(7): 1957-97.
[http://dx.doi.org/10.1089/ars.2010.3586] [PMID: 21087145]

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