Abstract
Background: Diabetic nephropathy can lead to renal diseases; oxidative stress and mitochondrial dysfunction have critical roles in its development.
Objectives: In this study, the effect of syringic acid (SYR), a natural phenolic acid, on diabetic nephropathy and mitochondrial biogenesis was examined. Methods: Diabetes was induced in rats by injecting streptozotocin. SYR (25, 50 and 100 mg/kg/day) was orally administered for 6 weeks. SYR effects on factors, such as antioxidant activities and mRNA expression level of mitochondrial biogenesis indexes, were evaluated. Results: In SYR-treated rats, blood glucose and ALP level were significantly reduced. SYR increased kidney GSH content in the diabetic group. Elevated renal catalase and superoxide dismutase activities in diabetic rats were restored to normal levels after treatment. SYR significantly reduced the renal TBARS level, which had increased in diabetic rats. This compound also significantly upregulated renal mRNA expression of PGC-1α and NRF-1, and increased mtDNA/nDNA ratio in diabetic rats. These values were reduced in the non-treated diabetic group. The results show improvement of histopathological damages of kidney in the SYR treated group in comparison with the diabetic group. Conclusion: According to the results, SYR alters renal antioxidant defense mechanisms. Also, it could be considered as a novel approach by targeting mitochondria in renal diabetic complications.Keywords: Syringic acid, diabetes, nephropathy, oxidative stress, biogenesis, mitochondrial dysfunction.
Graphical Abstract
[1]
Ye H-Y, Li Z-Y, Zheng Y, Chen Y, Zhou Z-H, Jin J. The attenuation of chlorogenic acid on oxidative stress for renal injury in streptozotocin-induced diabetic nephropathy rats. Arch Pharm Res 2016; 39(7): 989-97.
[2]
Duran-Salgado MB, Rubio-Guerra AF. Diabetic nephropathy and inflammation. World J Diabetes 2014; 5(3): 393.
[3]
Arora MK, Sarup Y, Tomar R, Singh M, Kumar P. Amelioration of diabetes-induced diabetic nephropathy by aloe vera: Implication of oxidative stress and hyperlipidemia. J Diet Suppl 2018; 1-18.
[4]
Bhargava P, Schnellmann RG. Mitochondrial energetics in the kidney. Nat Rev Nephrol 2017; 13(10): 629.
[5]
5. Y Li Y, Zhang L, Wang X, Wu W, Qin R. Effect of Syringic acid on antioxidant biomarkers and associated inflammatory markers in mice model of asthma. Drug Dev Res 2019; 80: 253-61.
[6]
Cikman O, Soylemez O, Ozkan OF, et al. Antioxidant activity of syringic acid prevents oxidative stress in l-arginine–induced acute pancreatitis: an experimental study on rats. Int surgery 2015; 100(5): 891-6.
[7]
Tanaka T, Kawaguchi N, Zaima N, Moriyama T, Fukuta Y, Shirasaka N. Antiosteoporotic activity of a syringic acid diet in ovariectomized mice. J Nat Med 2017; 71(4): 632-41.
[8]
Itoh A, Isoda K, Kondoh M, et al. Hepatoprotective effect of syringic acid and vanillic acid on CCl-induced liver injury. Biol Pharm Bulletin 2010; 33(6): 983-7.
[9]
Shi C, Sun Y, Zheng Z, et al. Antimicrobial activity of syringic acid against Cronobacter sakazakii and its effect on cell membrane. Food Chem 2016; 197: 100-6.
[10]
Ham JR, Lee H-I, Choi R-Y, Sim M-O, Seo K-I, Lee M-K. Anti-steatotic and anti-inflammatory roles of syringic acid in high-fat diet-induced obese mice. Food & Function 2016; 7(2): 689-97.
[11]
Arumugam B, Balagangadharan K, Selvamurugan N. Syringic acid, a phenolic acid, promotes osteoblast differentiation by stimulation of Runx2 expression and targeting of Smad7 by miR-21 in mouse mesenchymal stem cells. J Cell Commun Signal 2018; 12(3): 561-73.
[12]
Ha SJ, Lee J, Park J, et al. Syringic acid prevents skin carcinogenesis via regulation of NoX and EGFR signaling. Biochem Pharmacol 2018; 154: 435-45.
[13]
Muthukumaran J, Srinivasan S, Venkatesan RS, Ramachandran V, Muruganathan U. Syringic acid, a novel natural phenolic acid, normalizes hyperglycemia with special reference to glycoprotein components in experimental diabetic rats. J Acute Disease 2013; 2(4): 304-9.
[14]
Sancak EB, Akbas A, Silan C, Cakir DU, Turkon H, Ozkanli SS. Protective effect of syringic acid on kidney ischemia-reperfusion injury. Renal Failure 2016; 38(4): 629-35.
[15]
Sabahi Z, Khoshnood-Mansoorkhani MJ, Rahmani Namadi S, Moein M. Antidiabetic and Synergistic Effects Study of Anthocyanin Fraction from Berberis integerrima Fruit on Streptozotocin-Induced Diabetic Rats Model. Trends Pharm Sci 2016; 2(1): 43-50.
[16]
Khodaei F, Rashedinia M, Heidari R, Rezaei M, Khoshnoud MJ. Ellagic acid improves muscle dysfunction in cuprizone-induced demyelinated mice via mitochondrial Sirt3 regulation. Life Sci 2019; 237: 116954.
[17]
Arabsolghar R, Saberzadeh J, Khodaei F, Borojeni RA, Khorsand M, Rashedinia M. The protective effect of sodium benzoate on aluminum toxicity in PC12 cell line. Res Pharm Sci 2017; 12(5): 391.
[18]
Khodaei F, Kholghipour H, Hosseinzadeh M, Rashedinia M. Effect of sodium benzoate on liver and kidney lipid peroxidation and antioxidant enzymes in mice. J Reports Pharma Sci 2019; 8(2): 217.
[19]
Mima A. Inflammation and oxidative stress in diabetic nephropathy: new insights on its inhibition as new therapeutic targets. J Diabetes Res 2013.
[20]
Choi K-M, Yoo H-S. Amelioration of hyperglycemia-induced nephropathy by 3,3¢-diindolylmethane in diabetic mice. Molecules 2019; 24(24): 4474.
[21]
Kashihara N, Haruna YK, Kondeti VS, Kanwar Y. Oxidative stress in diabetic nephropathy. Curr Med Chem 2010; 17(34): 4256-69.
[22]
Pradeep SR, Srinivasan K. Alleviation of oxidative stress-mediated nephropathy by dietary fenugreek (Trigonella foenum-graecum) seeds and onion (Allium cepa) in streptozotocin-induced diabetic rats. Food & Function 2018.
[23]
Sabahi Z, Khoshnoud MJ, khalvati B, et al. Syringic acid improves oxidative stress and mitochondrial biogenesis in the liver of streptozotocin-induced diabetic rats. Asian Pac J Trop Biomed 2020; 10(3): 111.
[24]
Rodriguez de Sotillo DV, Hadley M. Chlorogenic acid modifies plasma and liver concentrations of: Cholesterol, triacylglycerol, and minerals in (fa/fa) Zucker rats. J Nutr Biochem 2002; 13(12): 717-26.
[25]
Cherng Y-G, Tsai C-C, Chung H-H, Lai Y-W, Kuo S-C, Cheng J-T. Antihyperglycemic action of sinapic acid in diabetic rats. Journal of Agricultural and Food Chemistry 2013; 61(49): 12053-9.
[26]
Choi R, Kim BH, Naowaboot J, et al. Effects of ferulic acid on diabetic nephropathy in a rat model of type 2 diabetes. Exp Mol Med 2011; 43(12): 676-83.
[27]
Punithavathi VR, Prince PSM, Kumar R, Selvakumari J. Antihyperglycaemic, antilipid peroxidative and antioxidant effects of gallic acid on streptozotocin induced diabetic Wistar rats. Eur J Pharmacol 2011; 650(1): 465-71.
[28]
Vinayagam R, Jayachandran M, Xu B. Antidiabetic effects of simple phenolic acids: A comprehensive review. Phytother Res 2016; 30(2): 184-99.
[29]
Jung EH, Ran Kim S, Hwang IK, Youl Ha T. Hypoglycemic effects of a phenolic acid fraction of rice bran and ferulic acid in C57BL/KsJ-db/db mice. J Agri Food Chem 2007; 55(24): 9800-4.
[30]
Wiwanitkit V. High serum alkaline phosphatase levels, a study in 181 Thai adult hospitalized patients. BMC Family practice 2001; 2(1): 2.
[31]
Oh SW, Han KH, Han SY. Associations between renal hyperfiltration and serum alkaline phosphatase. PloS one 2015; 10(4): e0122921.
[32]
Zhang S, Xu H, Yu X, Wu Y, Sui D. Metformin ameliorates diabetic nephropathy in a rat model of low-dose streptozotocin-induced diabetes. Exp Ther Med 2017; 14(1): 383-90.
[34]
Marzieh R, Hosseinzadeh H, Mohsen I, Parisa L, Bibi Marjan R, Khalil A. Effect of exposure to diazinon on adult rat’s brain. Toxicol Ind Health 2013.
[35]
Parhizkar E, Rashedinia M, Karimi M, Alipour S. Design and development of vitamin C-encapsulated proliposome with improved in-vitro and ex-vivo antioxidant efficacy. J microencapsul 2018; 35(3): 301-11.
[36]
Sasikala C, Sudhakar Y. Effect of compounds isolated from Filicium decipiens and Ventilago madraspatana against diabetic nephropathy in streptozotocin induced diabetic rats. Indian J Pharma Edu Res 2015; 49(2): 146-51.
[37]
Ahad A, Ganai AA, Mujeeb M, Siddiqui WA. Ellagic acid, an NF-κB inhibitor, ameliorates renal function in experimental diabetic nephropathy. Chemico-biological interactions 2014; 219: 64-75.
[38]
Sabahi Z, Soltani F, Moein M. Insight into DNA protection ability of medicinal herbs and potential mechanisms in hydrogen peroxide damages model. Asian Pac J Trop Biomed 2018; 8(2): 120-9.
[39]
Vondra K, Rath R, Bass A, Slabochova Z, Teisinger J, Vitek V. Enzyme activities in quadriceps femoris muscle of obese diabetic male patients. Diabetologia 1977; 13(5): 527-9.
[40]
Zamora M, Pardo R, Villena JA. Pharmacological induction of mitochondrial biogenesis as a therapeutic strategy for the treatment of type 2 diabetes. Biochem pharmacol 2015; 98(1): 16-28.
[41]
Rolo AP, Palmeira CM. Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress. Toxicol applied Pharmacol 2006; 212(2): 167-78.
[42]
Palikaras K, Tavernarakis N. Mitochondrial homeostasis: the interplay between mitophagy and mitochondrial biogenesis. Exp Gerontol 2014; 56: 182-8.
[43]
Kang J-W, Hong J-M, Lee S-M. Melatonin enhances mitophagy and mitochondrial biogenesis in rats with carbon tetrachloride-induced liver fibrosis. J Pineal Res 2016; 60(4): 383-93.
[44]
Guo K, Lu J, Huang Y, et al. Protective role of PGC-1α in diabetic nephropathy is associated with the inhibition of ROS through mitochondrial dynamic remodeling. PLoS One 2015; 10(4): e0125176.
[45]
Imasawa T, Obre E, Bellance N, et al. High glucose repatterns human podocyte energy metabolism during differentiation and diabetic nephropathy. FASEB J 2016; 31(1): 294-307.
[46]
Dugan LL, You Y-H, Ali SS, et al. AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J Clin Investig 2013; 123(11)
[47]
Yu J, Auwerx J. Protein deacetylation by SIRT1: An emerging key post-translational modification in metabolic regulation. Pharmacol Res 2010; 62(1): 35-41.
[48]
Rehman H, Krishnasamy Y, Haque K, et al. Green tea polyphenols stimulate mitochondrial biogenesis and improve renal function after chronic cyclosporin a treatment in rats. PLoS One 2013; 8(6): e65029.
[49]
Rasbach KA, Schnellmann RG. Isoflavones promote mitochondrial biogenesis. J Pharmacol Exp Ther 2008; 325(2): 536-43.
[50]
Csiszar A, Labinskyy N, Pinto JT, et al. Resveratrol induces mitochondrial biogenesis in endothelial cells. Am J Physiol - Heart and Circ Physiol 2009; 297(1): H13-20.
Article Metrics
18
1