Protective Effects of Tricin Against Oxldl-Stimulated Inflammatory and Oxidative Stress Responses in RAW 264.7 Cells
Main Article Content
Abstract
Oxidized low density lipoprotein (OxLDL) induced macrophage activation plays a major role in inflammatory and oxidative stress mediated disorders. The present study investigated the protective effect of tricin against OxLDL stimulated inflammatory and oxidative stress responses in RAW 264.7 cells. RAW 264.7 macrophages were pretreated with tricin (15 µM) or quercetin (25 µM) 1 h prior to OxLDL stimulation (50 µg/ml) and incubated for 24 h. DAPI staining revealed nuclear condensation and altered nuclear morphology in OxLDL treated cells, indicating cellular stress and inflammatory injury, whereas tricin treatment cells preserved nuclear integrity and reduced cellular damage. OxLDL stimulation significantly increased, total COX activity, PGE₂ levels MPO activity, MDA levels, and the pro-inflammatory cytokines TNF-α and IL-1β, while reducing SOD activity and anti- inflammatory cytokines IL-10 and TGF-β. Tricin treatment markedly suppressed total COX activity, PGE₂ production, MPO activity, lipid peroxidation, and inflammatory cytokine levels, while restoring antioxidant defence through increased SOD activity and anti-inflammatory cytokine levels. The findings of the present study demonstrated that tricin possesses significant anti-inflammatory and antioxidant activities against OxLDL-induced macrophage injury and may serve as a promising natural therapeutic agent for OxLDL associated inflammatory disorders.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
I. Ahmed AU. An overview of inflammation: mechanism and consequences. Front Biol. 2011;6(4):274–281. https://doi.org/10.1007/s11515-011-1123-9.
II. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal. 2014;20(7):1126–1167. https://doi.org/10.1089/ars.2012.5149.
III. Yu XH, Fu YC, Zhang DW, Yin K, Tang CK. Foam cells in atherosclerosis. Clin Chim Acta. 2013;424:245–252. https://doi.org/10.1016/j.cca.2013.06.006.
IV. Poznyak AV, Nikiforov NG, Markin AM, Kashirskikh DA, Myasoedova VA, Gerasimova EV, et al. Overview of OxLDL and its impact on cardiovascular health: focus on atherosclerosis. Front Pharmacol. 2020;11:613780. https://doi.org/10.3389/fphar.2020.613780.
V. Mushenkova NV, Bezsonov EE, Orekhova VA, Popkova TV, Starodubova AV, Orekhov AN. Recognition of oxidized lipids by macrophages and its role in atherosclerosis development. Biomedicines. 2021;9(8):915. https://doi.org/10.3390/biomedicines9080915.
VI. Li XX, Chen SG, Yue GGL, Kwok HF, Lee JKM, Zheng T, et al. Natural flavone tricin exerted anti-inflammatory activity in macrophage via NF-κB pathway and ameliorated acute colitis in mice. Phytomedicine. 2021;90:153625. https://doi.org/10.1016/j.phymed.2021.153625.
VII. Lara-Guzmán OJ, Gil-Izquierdo Á, Medina S, Osorio E, Álvarez-Quintero R, Zuluaga N, et al. Oxidized LDL triggers changes in oxidative stress and inflammatory biomarkers in human macrophages. Redox Biol. 2018;15:1–11. https://doi.org/10.1016/j.redox.2017.12.017.
VIII. Shalini V, Jayalekshmi A, Helen A. Mechanism of anti-inflammatory effect of tricin, a flavonoid isolated from Njavara rice bran in LPS induced hPBMCs and carrageenan induced rats. Mol Immunol. 2015;66(2):229–239. https://doi.org/10.1016/j.molimm.2015.03.004.
IX. Li B, Ji Y, Yi C, Wang X, Liu C, Wang C, et al. Rutin inhibits OxLDL-mediated macrophage inflammation and foam cell formation by inducing autophagy and modulating PI3K/AKT signaling. Molecules. 2022;27(13):4201. https://doi.org/10.3390/molecules27134201.
X. Havel RJ, Eder HA, Bragdon JH. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955;34:1345–1353. https://doi.org/10.1172/JCI103182.
XI. Nguyen-Khoa T, Massy ZA, Witko-Sarsat V, Canteloup S, Kebede M, Lacour B, et al. Oxidized low-density lipoprotein induces macrophage respiratory burst via its protein moiety: a novel pathway in atherogenesis? Biochem Biophys Res Commun. 1999;263(3):804–809. https://doi.org/10.1006/bbrc.1999.1438.
XII. Shalini V, Bhaskar S, Kumar KS, Mohanlal S, Jayalekshmy A, Helen A, et al. Molecular mechanisms of anti-inflammatory action of the flavonoid, tricin from Njavara rice (Oryza sativa L.) in human peripheral blood mononuclear cells: Possible role in the inflammatory signaling. Int Immunopharmacol. 2012;14(1):32–38. https://doi.org/10.1016/j.intimp.2012.06.005.
XIII. Bhaskar S, Kumar KS, Krishnan K, Antony H. Quercetin alleviates hypercholesterolemic diet induced inflammation during progression and regression of atherosclerosis in rabbits. Nutrition. 2013;29(1):219–229. https://doi.org/10.1016/j.nut.2012.01.019.
XIV. Kapuscinski J. DAPI: a DNA-specific fluorescent probe. Biotech Histochem. 1995;70(5):220–233. https://doi.org/10.3109/10520299509108199.
XV. Engvall E, Perlmann P. Enzyme-linked immunosorbent assay (ELISA): quantitative assay of immunoglobulin G. Immunochemistry. 1971;8(9):871–874. https://doi.org/10.1016/0019-2791(71)90454-X.
XVI. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265–275. https://doi.org/10.1016/S0021-9258(19)52451-6.
XVII. Shimizu T, Kondo K, Hayaishi O. Role of prostaglandin endoperoxides in the serum thiobarbituric acid reaction. Arch Biochem Biophys. 1981;206(1):271–276. https://doi.org/10.1016/0003-9861(81)90091-6.
XVIII. Bradley PP, Christensen RD, Rothstein G. Cellular and extracellular myeloperoxidase in pyogenic inflammation. Blood. 1982;60(3):618–622. https://doi.org/10.1182/blood.V60.3.618.618.
XIX. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351–358. https://doi.org/10.1016/0003-2697(79)90738-3.
XX. Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys. 1984;21(2):130–132.
XXI. Steel RGD, Torrie JH, Dickey DA. Principles and Procedures of Statistics: A Biometrical Approach. 3rd ed. New York: McGraw-Hill; 1997.
XXII. Zhang H, Zhai Z, Zhou H, Li Y, Li X, Lin Y, et al. Puerarin inhibits OxLDL-induced macrophage activation and foam cell formation in human THP-1 macrophage. Biomed Res Int. 2015;2015:403616. https://doi.org/10.1155/2015/403616.