Grape Seed Proanthocyanidins Ameliorate Diabetic Nephropathy via Modulation of Levels of AGE, RAGE and CTGF

Abstract

Background: Diabetic nephropathy (DN) is the most common cause of end-stage renal failure. Grape seed proanthocyanidin extracts (GSPE) are powerful antioxidants. However, the role of GSPE on advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE) and expression of connective tissue growth factor (CTGF) in DN has not been elucidated. Using streptozotocin-induced diabetic rats, we evaluated the effects of GSPE in DN. Methods: Wistar rats were induced into diabetes using streptozotocin injections and diabetic rats were treated with GSPE (dosage: 500 mg·kg^–1·day^–1) for 24 weeks. The renal pathological changes were examined with PAS staining and electron microscope. The mRNA and protein expression of RAGE and CTGF in kidney were detected by RT-PCR, Western blot and immunohistochemical staining. Results: Treated animals showed reduction in serum AGEs (p < 0.01), proteinuria (p < 0.01) and systolic blood pressure (p < 0.01). GSPE reduced the expression of RAGE (p < 0.01) and CTGF (p < 0.01) in the kidney, which were contributing to reversal of extracellular matrix accumulation in DN. Conclusion: Our results suggest that GSPE hold substantial promise for the treatment of DN. GSPE can decrease proteinuria, attenuating the progression of nephropathy in diabetic rats. Renoprotective effects of GSPE are correlated with suppression on AGEs/RAGE axis, downregulating expression of CTGF.

Purple sweet potato (Ipomoea batatas L.) color alleviates high-fat-diet-induced obesity in SD rat by mediating leptin’s effect and attenuating oxidative stress

“…Immunofluorescence results showed that RAGE directly binds with TXNIP, indicating that related regulatory triggering occurs among ROS, RAGE, and TXNIP. PSPC effectively eliminated the obesity that was induced by administration of a HFD and treatment efficacy was achieved based on attenuation of oxidative stress and dampening of the RAGE/TXNIP signaling pathway, similar to recent reports (16,25).…”

Grape Seed Proanthocyanidin Extracts Enhance Endothelial Nitric Oxide Synthase Expression through 5′-AMP Activated Protein Kinase/Surtuin 1–Krüpple Like Factor 2 Pathway and Modulate Blood Pressure in Ouabain Induced Hypertensive Rats

“…The superoxide anion scavenging activity of GSPE was stronger than vitamin C, vitamin E or any other antioxidant. 1) It has been reported to have protective effects on various cardiac disorders, correct dyslipidemia associated with high-fat diet, 2) decrease arterial pressure in estrogen-depleted female spontaneously hypertensive rats, 3) prevent diabetic nephropathy and neuropathy from progressing, 4,5) and most importantly, ameliorate atherosclerosis, 6) possibly attributed to its endothelial protective potential.…”

Edible plants from traditional Chinese medicine is a promising alternative for the management of diabetic nephropathy

“…For in vitro studies, there are many DN models commonly used in TCM edible plants, such as mouse embryonic fibroblastadipose like cells (3T3-L1), L6 myotubes, human mesangial cells, mouse mesangial cells (MES-13), mouse podocyte cells, murine skeletal myoblasts (C2C12), murine hepatocytes (H4IIE), renal proximal tubular epithelial cells (HK-2), rat insulinoma cells (INS-1), glomerular endothelial cells, and vascular endothelial cells (Eid et al, 2010;Lee et al, 2010;Li et al, 2009Li et al, , 2010 Yu, Gao, & Liu, 2010;Zhang, Liu, Xiong, Gong, & Tan, 2012). All these in vivo and in vitro models enhance our understanding of the mechanisms of the protective effects of TCM edible plants against DN.…”

“…Experimental studies also demonstrated the nephro-protective effect of ginger in STZ-induced diabetic rat via regulating intra-and extra-mitochondrial enzymes (Ramudu et al, 2011). Strikingly, grape seed proanthocyanidins showed a pronounced therapeutic effect on experimental DN through multiple cellular targets (Cheng et al, 2007;Li et al, 2009;Liu, Shen, & Yao, 2006;Mansouri et al, 2011). Furthermore, the formation of AGEs was inhibited in db/ db mice after treatment with Pu-erh tea (Yan et al, 2012).…”

“…Recent evidence indicates that TCM edible plants such as Panax notoginseng, Cinnamomum zeylanicum and Astragalus membranaceus have significant potential to modulate DN progression Gao et al, 2012;Liu, Xu, Shen, & Wu, 2012;Tang et al, 2011;Tu, Qin, Dong, Lu, & Guan, 2011). Moreover, many TCM edible plants such as mushroom, grape, hawthorn etc., demonstrate a preferable benefit for DN patients Li et al, 2009;Mooradian, Failla, Hoogwerf, Maryniuk, & Wylie-Rosett, 1994). Since many TCM herbs are edible and the concept of diet therapy is widely accepted, the introduction of edible plants from TCM as dietary therapy would be a promising alternative for DN management.…”