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Yazdi M, Nafari A, Azadpour M, Alaee M, Hadipour Moradi F, Choghakhori R, et al . Protective Effects of Cinnamic Acid Against Hyperglycemia Induced Oxidative Stress and Inflammation in HepG2 Cells. rbmb.net 2023; 12 (1) :1-12
URL: http://rbmb.net/article-1-914-en.html
Department of Biochemistry, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran & Medicinal plants and natural products research center, Hamadan university of medical sciences, Hamadan, Iran.
Abstract:   (1295 Views)
Background: Cinnamic acid, a phenylpropanoid acid, has been investigated as a potential alternative therapy for diabetes and its complications in some studies. 

Methods: In the first stage, the viability of HepG2 cells at different concentrations of glucose and CA was assessed by MTT assay. Oxidative stress markers) CAT, GPx, GSH, and MDA) were measured spectrophotometrically. After RNA extraction, the effect of different concentrations of CA on the expression of DPP4 and inflammatory factors (IL-6, NF- κB) in HepG2 cells was assessed using real-time PCR.

Results: In HepG2 cells, CA increased catalase and glutathione peroxidase activity and GSH production in a dose-dependent manner in the presence of high glucose concentrations, with the greatest effect seen at a concentration of 75 mg/ml. Also, it reduced the amount of MDA in high-glucose HepG2 cells. Furthermore, CA decreased the expression of DPP4, NF- κB, and IL-6 genes in HepG2 cells in the presence of high glucose levels.

Conclusions: The results of our study indicated that CA reduced hyperglycemia-induced complications in HepG2 cells by decreasing inflammatory gene expression, including IL-6 and NF- κB and inhibiting the expression of DPP4, and limiting oxidative stress.
Full-Text [PDF 462 kb]   (920 Downloads)    
Type of Article: Original Article | Subject: Biochemistry
Received: 2022/04/13 | Accepted: 2022/04/21 | Published: 2023/08/15

References
1. De P, Baltas M, Bedos-Belval F. Cinnamic acid derivatives as anticancer agents-a review. Curr Med Chem. 2011;18(11):1672-703. [DOI:10.2174/092986711795471347] [PMID]
2. Akao Y, Maruyama H, Matsumoto K, Ohguchi K, Nishizawa K, Sakamoto T, et al. Cell growth inhibitory effect of cinnamic acid derivatives from propolis on human tumor cell lines. Biol Pharm Bull. 2003;26(7):1057-9. [DOI:10.1248/bpb.26.1057] [PMID]
3. Lee EJ, Kim SR, Kim J, Kim YC. Hepatoprotective phenylpropanoids from Scrophularia buergeriana roots against CCl4-induced toxicity: action mechanism and structure-activity relationship. Planta Med. 2002;68(05):407-11. [DOI:10.1055/s-2002-32081] [PMID]
4. Lee H-S. Tyrosinase inhibitors of Pulsatilla cernua root-derived materials. J Agric Food Chem. 2002;50(6):1400-3. [DOI:10.1021/jf011230f] [PMID]
5. Liu IM, Hsu FL, Chen CF, Cheng JT. Antihyperglycemic action of isoferulic acid in streptozotocin‐induced diabetic rats. Br J Pharmacol.2000;129(4):631-6. [DOI:10.1038/sj.bjp.0703082] [PMID] [PMCID]
6. Sova M. Antioxidant and antimicrobial activities of cinnamic acid derivatives. Mini Rev Med Chem. 2012;12(8):749-67. [DOI:10.2174/138955712801264792] [PMID]
7. Wiesner J, Mitsch A, Wißner P, Jomaa H, Schlitzer M. Structure-activity relationships of novel anti-malarial agents. Part 2: Cinnamic acid derivatives. Bioorg Med Chem Lett. 2001;11(3):423-4. [DOI:10.1016/S0960-894X(00)00684-3] [PMID]
8. Zhang L, Ji Z. Synthesis, antiinflammatory and anticancer activity of cinnamic acids, their derivatives and analogues. Yao xue xue bao= Acta pharmaceutica Sinica. 1992;27(11):817-23.
9. Buse JB, Wexler DJ, Tsapas A, Rossing P, Mingrone G, Mathieu C, et al. 2019 update to: management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes care. 2020;43(2):487-93. [DOI:10.2337/dci19-0066] [PMID] [PMCID]
10. Wolff S. Diabetes mellitus and free radicals: free radicals, transition metals and oxidative stress in the aetiology of diabetes mellitus and complications. Br Med Bull. 1993;49(3):642-52. [DOI:10.1093/oxfordjournals.bmb.a072637] [PMID]
11. Wei W, Liu Q, Tan Y, Liu L, Li X, Cai L. Oxidative stress, diabetes, and diabetic complications. Hemoglobin. 2009;33(5):370-7. [DOI:10.3109/03630260903212175] [PMID]
12. Kwiecien S, Jasnos K, Magierowski M, Sliwowski Z, Pajdo R, Brzozowski B, et al. Lipid peroxidation, reactive oxygen species and antioxidative factors in the pathogenesis of gastric mucosal lesions and mechanism of protection against oxidative stress-induced gastric injury. J Physiol Pharmacol. 2014;65(5):613-22.
13. Kazakos K. Incretin Effect: Glp-1, Gip, Dpp4. D Diabetes Res Clin Pract. 2011;93:S32-S6. [DOI:10.1016/S0168-8227(11)70011-0] [PMID]
14. Goyal R, Faizy AF, Siddiqui SS, Singhai M. Evaluation of TNF-α and IL-6 levels in obese and non-obese diabetics: pre-and postinsulin effects. N Am J Med Sci. 2012;4(4):180. [DOI:10.4103/1947-2714.94944] [PMID] [PMCID]
15. Borst SE. The role of TNF-α in insulin resistance. Endocrine. 2004;23(2):177-82. [DOI:10.1385/ENDO:23:2-3:177] [PMID]
16. Mohammadi M, Gozashti MH, Aghadavood M, Mehdizadeh MR, Hayatbakhsh MM. Clinical Significance of Serum IL-6 and TNF-α Levels in Patients with Metabolic Syndrome. Rep Biochem Mol Biol. 2017;6(1):74-79.
17. Senn JJ, Klover PJ, Nowak IA, Mooney RA. Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes. 2002;51(12):3391-9. [DOI:10.2337/diabetes.51.12.3391] [PMID]
18. Patel S, Santani D. Role of NF-κB in the pathogenesis of diabetes and its associated complications. Pharmacol Rep. 2009;61(4):595-603. [DOI:10.1016/S1734-1140(09)70111-2] [PMID]
19. Khosrowbeygi A, Ahmadvand H. Circulating levels of homocysteine in preeclamptic women. Bangladesh Med Res Counc Bull. 2011;37(3):106-9. [DOI:10.3329/bmrcb.v37i3.6196] [PMID]
20. Luc K, Schramm-Luc A, Guzik T, Mikolajczyk T. Oxidative stress and inflammatory markers in prediabetes and diabetes. J Physiol Pharmacol. 2019;70(6):809-24.
21. Kumar SM, Haridoss M, Swaminathan K, Gopal RK, Clemens D, Dey A. The effects of changes in glutathione levels through exogenous agents on intracellular cysteine content and protein adduct formation in chronic alcohol-treated VL17A cells. Toxicol Mech Methods. 2017;27(2):128-35. [DOI:10.1080/15376516.2016.1268229] [PMID]
22. Adisakwattana S. Cinnamic acid and its derivatives: mechanisms for prevention and management of diabetes and its complications. Nutrients. 2017;9(2):163. [DOI:10.3390/nu9020163] [PMID] [PMCID]
23. Song F, Li H, Sun J, Wang S. Protective effects of cinnamic acid and cinnamic aldehyde on isoproterenol-induced acute myocardial ischemia in rats. J Ethnopharmacol. 2013;150(1):125-30. [DOI:10.1016/j.jep.2013.08.019] [PMID]
24. Liao J-C, Deng J-S, Chiu C-S, Hou W-C, Huang S-S, Shie P-H, Huang G-J. Anti-inflammatory activities of Cinnamomum cassia constituents in vitro and in vivo. Evidence-Based Complementary and Alternative Medicine. 2012;2012. [DOI:10.1155/2012/429320] [PMID] [PMCID]
25. Pontiki E, Hadjipavlou-Litina D. Multi-Target Cinnamic Acids for Oxidative Stress and Inflammation: Design, Synthesis, Biological Evaluation and Modeling Studies. Molecules. 2018;24(1):12. [DOI:10.3390/molecules24010012] [PMID] [PMCID]
26. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J immunol methods. 1983;65(1-2):55-63. [DOI:10.1016/0022-1759(83)90303-4] [PMID]
27. Cheraghi M, Ahmadvand H, Maleki A, Babaeenezhad E, Shakiba S, Hassanzadeh F. Oxidative Stress Status and Liver Markers in Coronary Heart Disease. Rep Biochem Mol Biol. 2019;8(1):49-55.
28. Ani M, Moshtaghie AA, Ahmadvand H. Comparative effects of copper, iron, vanadium and titanium on low density lipoprotein oxidation in vitro. Iran Biomed J. 2007;11(2):113-118.
29. Reck-Peterson SL, Derr ND, Stuurman N. Imaging single molecular motor motility with total internal reflection fluorescence microscopy (TIRFM). Cold Spring Harb Protoc. 2010;2010(3):pdb.prot5399. [DOI:10.1101/pdb.prot5399] [PMID]
30. Röhrborn D, Wronkowitz N, Eckel J. DPP4 in diabetes. Frontiers in immunology. 2015;6:386. [DOI:10.3389/fimmu.2015.00386] [PMID] [PMCID]
31. Adolpho LO, Marin D, Puigpinos A, Mendieta L, Tarragó T, Morel AF, et al. In vitro evaluation of caffeoyl and cinnamoyl derivatives as potential prolyl oligopeptidase inhibitors. Planta medica. 2013;79(16):1531-5. [DOI:10.1055/s-0033-1350897] [PMID]
32. Mehta V, Verma P, Sharma N, Sharma A, Thakur A, Malairaman U. Quercetin, ascorbic acid, caffeine and ellagic acid are more efficient than rosiglitazone, metformin and glimepiride in interfering with pathways leading to the development of neurological complications associated with diabetes: A comparative in-vitro study. Bulletin of Faculty of Pharmacy, Cairo University. 2017;55(1):115-21. [DOI:10.1016/j.bfopcu.2016.12.002]
33. Panahi G, Pasalar P, Zare M, Rizzuto R, Meshkani R. High glucose induces inflammatory responses in HepG2 cells via the oxidative stress-mediated activation of NF-κB, and MAPK pathways in HepG2 cells. Arch Physiol Biochem. 2018;124(5):468-74. [DOI:10.1080/13813455.2018.1427764] [PMID]
34. Gabriele E, Brambilla D, Ricci C, Regazzoni L, Taguchi K, Ferri N, et al. New sulfurated derivatives of cinnamic acids and rosmaricine as inhibitors of STAT3 and NF-κB transcription factors. J Enzyme Inhib Med Chem. 2017;32(1):1012-28. [DOI:10.1080/14756366.2017.1350658] [PMID] [PMCID]
35. Ahmadvand H, Amiri H, Elmi ZD, Bagheri S. Chemical composition and antioxidant properties of Ferula-assa-foetida leaves essential oil. Iran J Pharmacol Ther. 2013;12(2):52-57.
36. Li X, Wen Z, He X, He S. Effects of cinnamic acid on expression of tissue factor induced by TNFα in endothelial cells and its mechanisms. J Chin Med Assoc. 2006;69(5):207-12. [DOI:10.1016/S1726-4901(09)70220-5] [PMID]
37. Chakrabarti S, Jana M, Roy A, Pahan K. Upregulation of suppressor of cytokine signaling 3 in microglia by cinnamic acid. Curr Alzheimer Res. 2018;15(10):894-904. [DOI:10.2174/1567205015666180507104755] [PMID] [PMCID]
38. Subramaniyan SD, kumar Natarajan A. Citral, a monoterpene protect against high glucose induced oxidative injury in HepG2 cell in vitro-an experimental study. J Clin Diagn Res. 2017;11(8):BC10. [DOI:10.7860/JCDR/2017/28470.10377] [PMID] [PMCID]
39. Anlar HG, Bacanli M, Çal T, Aydin S, Ari N, Bucurgat ÜÜ, et al. Effects of cinnamic acid on complications of diabetes. Turk J Med Sci. 2018;48(1):168-77. [DOI:10.3906/sag-1708-8] [PMID]

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