Pharmacognostic Evaluation of Curcumin on Diabetic Retinopathy in Alloxan-induced Diabetes through NF-KB and Brn3a Related Mechanism

Abstract

Background: Diabetic retinopathy is one of the most common micro vascular complication of diabetes and involves an abnormal pathology of major retinal pigment epithelium, inter retinal oedema and intraocular neovascularisation where pro-inflammatory proteins including ICAM-1,iNOS and VEGF release by activation of enzyme CaMKII/NF-kB expression Diabetic induced oxidative stress followed by deactivation of Brn3a expression in the retinal ganglionic cells are also early events in pathogenesis of Diabetic retinopathy. These factors are important contributors to the development of clinically significant diabetic retinopathy. Objective: Objective of this study to examine the effect of curcumin with antioxidant and anti-inflammatory properties obtained from Curcuma longa against diabetes-induced retinal vascular damage and its mechanism of action by in-vivo in retinas of rat rendered diabetic by alloxan and in vitro in western blotting and RGC tissue culture. Method: We administered curcumin or saline vehicle to experimental animals daily for 12 weeks. Vascular permeability, expression of CaMK II/NF-kB, Retinal morphology and neuropathic change of the retinal ganglion cells were investigated. Results: As an anti-oxidant, curcumin raised Retinal Ganglionic cells by increasing Brn3a expression during oxidative stress condition and subsequently decreased the expression of inflammatory mediators such as VEGF, iNOS and ICAM-1 as an anti-inflammatory agent by inhibiting CaMKII and NF-kB expression. Conclusion: Curcumin, a common food additive has beneficial effects in experimental studies of diseases that are characterised by increased oxidative stress and inflammatory reactions. It appears to be a useful adjunct therapy to possibly inhibit the progression of retinopathy, sight threatening complication faced by diabetic patients.

Therapeutic potential of curcumin in diabetic retinopathy (Review)

“…In a previous study, following treatment with curcumin, a significant reduction in the thickness of the retinal capillary basement membrane was observed in diabetic rats treated with curcumin, but not in the untreated diabetic rats ( 70 ). Some scholars have confirmed that curcumin can reduce the expression of VEGF, inducible nitric oxide synthase (iNOS) and ICAM-1 by inhibiting the activation of CaMKII/NF-κB signaling in the diabetic rat retina and in Müller cells cultured in high glucose ( 71 , 72 ). Curcumin not only exerts anti-VEGF effects on the retina, but also exerts anti-angiogenetic effects on the choroidal vascular system of diabetic rats.…”

Nutraceuticals for the Treatment of Diabetic Retinopathy

“…Curcumin also reduces retinal diabetic damage in diabetic rats through inactivation of NF-κB and a decrease in IL-1β levels [38]. There is some indication that curcumin may influence NF-κB by preventing the diabetes-induced retinal activation of calcium/calmodulin-dependent protein kinase II (CAMKII) [27,74,75,76], a ubiquitous multifunctional protein kinase implicated in the regulation of the transcriptional activity of NF-κB [77]. Curcumin has also been observed to reverse the diabetes-induced upregulation of retinal GFAP in Müller cells of STZ rats [36].…”

Nature against Diabetic Retinopathy: A Review on Antiangiogenic, Antioxidant, and Anti-Inflammatory Phytochemicals

“…In HG-induced ARPE-19 cells, curcumin treatment significantly reduced ROS production [ 12 ]. Consumption of curcumin in alloxan-induced DR rats increased the number of retinal ganglion cells under oxidative stress by increasing Brn3a expression [ 56 ]. Docosahexanoic acid (DHA) is a polyunsaturated fatty acid that is synthesized from the plant linolenic acid's fatty acid and is essential for the growth and development of the brain and retina that is also beneficial for pregnancy and lactation [ 57 , 58 ].…”