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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Research Article

Procyanidin B2 Protects TR-iBRB2 Cells Against Hyperglyc emia Stress by Attenuating Oxidative Stress and Inflammasome Activation via Regulation of Redoxosomes/NF-kB Signaling

Author(s): Wenjun Zou, Qianyi Lu, Xue Zhu, Ying Pan, Quan Xu* and Ke Wang*

Volume 23, Issue 10, 2023

Published on: 27 October, 2022

Page: [1095 - 1103] Pages: 9

DOI: 10.2174/1566524023666221017120334

Price: $65

Abstract

Background: Microvascular dysfunction is a hallmark of diabetic retinopathy (DR), which may lead to visual impairment and blindness. Procyanidin B2 (PB2) is a subclass of flavonoids and is widely known due to its anti-oxidant and antiinflammatory effects. However, little is known about the effect of PB2 on hyperglycemia stress-induced retinal microvascular dysfunction.

Objective: The purpose of this study was to investigate the effect of PB2 against hyperglycemia stress in rat retinal capillary endothelial cells (TR-iBRB2) as well as the underpinning mechanism.

Methods: Cell viability was determined using MTT assay. ROS, NOX activity analysis, Western blot analysis, and immunofluorescence analysis were applied in the study.

Results: The results showed that PB2 pre-treatment significantly reduced high glucose- induced cytotoxicity in TR-iBRB2 cells by suppressing oxidative stress and inflammasome activation. Mechanistical study revealed that redoxosomes were formed and activated in TR-iBRB2 cells upon hyperglycemia stress, resulting in activation of NF- κB and thus induction of oxidative stress and inflammasomes activation. However, PB2 pre-treatment dose-dependently attenuated the above events, indicating the protective effect of PB2 against hyperglycemia stress was achieved by regulating redoxosomes/ NF-kB signaling.

Conclusion: Our findings may contribute to the potential clinical use of PB2 in treating DR and suggest redoxosomes/NF-kB signaling may be a potential therapeutic target of this disease.

« Previous Next »
[1]
Sivaprasad S, Gupta B, Crosby-Nwaobi R, Evans J. Prevalence of diabetic retinopathy in various ethnic groups: A worldwide perspective. Surv Ophthalmol 2012; 57(4): 347-70.
[http://dx.doi.org/10.1016/j.survophthal.2012.01.004] [PMID: 22542913]
[2]
Duh EJ, Sun JK, Stitt AW. Diabetic retinopathy: Current understanding, mechanisms, and treatment strategies. JCI Insight 2017; 2(14): e93751.
[http://dx.doi.org/10.1172/jci.insight.93751] [PMID: 28724805]
[3]
Sorrentino FS, Matteini S, Bonifazzi C, Sebastiani A, Parmeggiani F. Diabetic retinopathy and endothelin system: Microangi-opathy versus endothelial dysfunction. Eye 2018; 32(7): 1157-63.
[http://dx.doi.org/10.1038/s41433-018-0032-4] [PMID: 29520046]
[4]
Nentwich MM, Ulbig MW. Diabetic retinopathy - ocular complications of diabetes mellitus. World J Diabetes 2015; 6(3): 489-99.
[http://dx.doi.org/10.4239/wjd.v6.i3.489] [PMID: 25897358]
[5]
Cho H, Alwassia AA, Regiatieri CV, et al. Retinal neovascularization secondary to proliferative diabetic retinopathy character-ized by spectral domain optical coherence tomography. Retina 2013; 33(3): 542-7.
[http://dx.doi.org/10.1097/IAE.0b013e3182753b6f] [PMID: 23400083]
[6]
Ishibazawa A, Nagaoka T, Yokota H, et al. Characteristics of retinal neovascularization in proliferative diabetic retinopathy im-aged by optical coherence tomography angiography. Invest Ophthalmol Vis Sci 2016; 57(14): 6247-55.
[http://dx.doi.org/10.1167/iovs.16-20210] [PMID: 27849310]
[7]
Paulus YM, Sodhi A. Anti-angiogenic therapy for retinal disease. Handb Exp Pharmacol 2016; 242: 271-307.
[http://dx.doi.org/10.1007/164_2016_78] [PMID: 27783271]
[8]
Rodríguez-Carrizalez AD, Castellanos-González JA, Martínez-Romero EC, et al. Oxidants, antioxidants and mitochondrial func-tion in non-proliferative diabetic retinopathy. J Diabetes 2014; 6(2): 167-75.
[http://dx.doi.org/10.1111/1753-0407.12076] [PMID: 23875878]
[9]
Rübsam A, Parikh S, Fort P. Role of inflammation in diabetic retinopathy. Int J Mol Sci 2018; 19(4): 942.
[http://dx.doi.org/10.3390/ijms19040942] [PMID: 29565290]
[10]
Oakley FD, Abbott D, Li Q, Engelhardt JF. Signaling components of redox active endosomes: The redoxosomes. Antioxid Redox Signal 2009; 11(6): 1313-33.
[http://dx.doi.org/10.1089/ars.2008.2363] [PMID: 19072143]
[11]
Yin J, Wang K, Zhu X, et al. Procyanidin B2 suppresses hyperglycemia induced renal mesangial cell dysfunction by modulat-ing CAV 1 dependent signaling. Exp Ther Med 2022; 24(2): 496.
[http://dx.doi.org/10.3892/etm.2022.11423] [PMID: 35837062]
[12]
Rodríguez-Ramiro I, Ramos S, Bravo L, Goya L, Martín MÁ. Procyanidin B2 and a cocoa polyphenolic extract inhibit acryla-mide-induced apoptosis in human Caco-2 cells by preventing oxidative stress and activation of JNK pathway. J Nutr Biochem 2011; 22(12): 1186-94.
[http://dx.doi.org/10.1016/j.jnutbio.2010.10.005] [PMID: 21334869]
[13]
Kopustinskiene DM, Savickas A, Vetchý D, Masteikova R, Kasauskas A, Bernatoniene J. Direct effects of (-)-epicatechin and procyanidin B2 on the respiration of rat heart mitochondria. BioMed Res Int 2015; 2015: 1-7.
[http://dx.doi.org/10.1155/2015/232836] [PMID: 25811024]
[14]
Yin W, Li B, Li X, et al. Anti-inflammatory effects of grape seed procyanidin B2 on a diabetic pancreas. Food Funct 2015; 6(9): 3065-71.
[http://dx.doi.org/10.1039/C5FO00496A] [PMID: 26207855]
[15]
Gouvêa CMCP, Avelar MM. Procyanidin B2 cytotoxicity to MCF-7 human breast adenocarcinoma cells. Indian J Pharm Sci 2012; 74(4): 351-5.
[http://dx.doi.org/10.4103/0250-474X.107070] [PMID: 23626391]
[16]
Zhang JQ, Wang XW, Chen JF, et al. Grape seed procyanidin B2 protects porcine ovarian granulosa cells against oxidative stress-induced apoptosis by upregulating let-7a expression. Oxid Med Cell Longev 2019; 2019: 1-17.
[http://dx.doi.org/10.1155/2019/1076512] [PMID: 31827667]
[17]
Yang H, Xiao L, Yuan Y, et al. Procyanidin B2 inhibits NLRP3 inflammasome activation in human vascular endothelial cells. Biochem Pharmacol 2014; 92(4): 599-606.
[http://dx.doi.org/10.1016/j.bcp.2014.10.001] [PMID: 25450671]
[18]
Reddy GB, et al. Antiglycating potential of procyanidin-B2 isolated from cinnamon bark: Prevention or treatment of diabetic ocular complications (cataract & retinopathy). Invest Ophthalmol Vis Sci 2013; 54(15): 1945-5.
[19]
Puppala M. Effect of cinnamon and its procyanidin-B2 on diabetic retinopathy in rats. Indian J Nutr Diet 2019; 56(2): 109-23.
[20]
Zhu X, Xie M, Wang K, et al. The effect of puerarin against IL-1β-mediated leukostasis and apoptosis in retinal capillary endo-thelial cells (TR-iBRB2). Mol Vis 2014; 20: 1815-23.
[PMID: 25593509]
[21]
Hosoya KI, Tomi M, Ohtsuki S, et al. Conditionally immortalized retinal capillary endothelial cell lines (TR-iBRB) expressing differentiated endothelial cell functions derived from a transgenic rat. Exp Eye Res 2001; 72(2): 163-72.
[http://dx.doi.org/10.1006/exer.2000.0941] [PMID: 11161732]
[22]
van Meerloo J, Kaspers GJL, Cloos J. Cell sensitivity assays: The MTT assay. Methods Mol Biol 2011; 731: 237-45.
[http://dx.doi.org/10.1007/978-1-61779-080-5_20] [PMID: 21516412]
[23]
Zheng Q, Ren Y, Reinach PS, et al. Reactive oxygen species activated NLRP3 inflammasomes initiate inflammation in hyper-osmolarity stressed human corneal epithelial cells and environment-induced dry eye patients. Exp Eye Res 2015; 134: 133-40.
[http://dx.doi.org/10.1016/j.exer.2015.02.013] [PMID: 25701684]
[24]
Karamitros CS, Lim J, Konrad M. An Amplex Red-based fluorometric and spectrophotometric assay for l-asparaginase using its natural substrate. Anal Biochem 2014; 445: 20-3.
[http://dx.doi.org/10.1016/j.ab.2013.09.028] [PMID: 24113285]
[25]
Fido RJ, Tatham AS, Shewry PR. Western blotting analysis.Plant Gene Transfer and Expression Protocols. New York: Springer 1996; pp. 423-37.
[26]
Duncan AE. Hyperglycemia and perioperative glucose management. Curr Pharm Des 2012; 18(38): 6195-203.
[http://dx.doi.org/10.2174/138161212803832236] [PMID: 22762467]
[27]
Kowluru RA, Chan PS. Oxidative stress and diabetic retinopathy. Exp Diabetes Res 2007; 2007: 1-12.
[http://dx.doi.org/10.1155/2007/43603] [PMID: 17641741]
[28]
Devi TS, Hosoya KI, Terasaki T, Singh LP. Critical role of TXNIP in oxidative stress, DNA damage and retinal pericyte apopto-sis under high glucose: Implications for diabetic retinopathy. Exp Cell Res 2013; 319(7): 1001-12.
[http://dx.doi.org/10.1016/j.yexcr.2013.01.012] [PMID: 23353834]
[29]
Calderon GD, Juarez OH, Hernandez GE, Punzo SM, De la Cruz ZD. Oxidative stress and diabetic retinopathy: Development and treatment. Eye 2017; 31(8): 1122-30.
[http://dx.doi.org/10.1038/eye.2017.64] [PMID: 28452994]
[30]
Carter BJ, Anklesaria P, Choi S, Engelhardt JF. Redox modifier genes and pathways in amyotrophic lateral sclerosis. Antioxid Redox Signal 2009; 11(7): 1569-86.
[http://dx.doi.org/10.1089/ars.2008.2414] [PMID: 19187001]
[31]
Torok NJ. Dysregulation of redox pathways in liver fibrosis. Am J Physiol Gastrointest Liver Physiol 2016; 311(4): G667-74.
[http://dx.doi.org/10.1152/ajpgi.00050.2016] [PMID: 27562057]
[32]
Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 1999; 91(15): 1310-6.
[http://dx.doi.org/10.1093/jnci/91.15.1310] [PMID: 10433620]
[33]
Morgan MJ, Liu Z. Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res 2011; 21(1): 103-15.
[http://dx.doi.org/10.1038/cr.2010.178] [PMID: 21187859]
[34]
Oakley FD, Smith RL, Engelhardt JF. Lipid rafts and caveolin-1 coordinate interleukin-1beta (IL-1beta)-dependent activation of NFkappaB by controlling endocytosis of Nox2 and IL-1beta receptor 1 from the plasma membrane. J Biol Chem 2009; 284(48): 33255-64.
[http://dx.doi.org/10.1074/jbc.M109.042127] [PMID: 19801678]

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