Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie Attenuation of diabetic retinopathy and neuropathy by resveratrol: Review on its molecular mechanisms of action Irshad Ahmad a , Muddasarul Hoda b, ⁎ a National Institute of Plant Genome Research, Aruna Asaf Ali Marg, New Delhi 110067, India b Department of Biological Sciences, Aliah University, IIA/27-Newtown, Kolkata 700160, India ARTICLEINFO Keywords: Resveratrol Phytochemicals Flavonoids Diabetic neuropathy Diabetic retinopathy ABSTRACT Resveratrol is an important phenolic phytochemical from the therapeutic perspective. It has therapeutic impacts over wide range of diseases, especially the ones related to oxidative stress. Resveratrol, being primarily a potent anti-oxidant phytochemical, has signifcant impact against major diseases as infammatory disorders, diabetes, and cancer. In the current review article, we intend to highlight the molecular aspects of the mechanism of action of resveratrol against major diabetic implications, namely, retinopathy and neuropathy. Both these dia- betic implications are among the frst fallouts of chronic hyperglycaemia. Resveratrol, via multiple molecular pathways, tend to attenuate and reverse these deformity and other disease-causing implications. 1. Introduction Glucose is the ultimate source of energy for our metabolic and physical activity. Its concentration in the blood is typically controlled by the alpha- and beta-cells of the pancreas, which secretes glucose- regulating hormones, insulin and glucagon respectively. Diabetes is a metabolic disorder that results from a chronically abnormal and sus- tained elevation of glucose concentration in the blood when observed during fasting as well as postprandial conditions. Diabetes may be broadly classifed into type-1 and type-2. In type-1 diabetes, complete or relative insufciency of insulin occurs due to autoimmune mediated destruction of β-cells [1]. It is < 10% of all kinds of diabetes cases, and the patients are dependent on exogenous insulin supply, where as 90% of diabetes cases belong to the type-2 kind [2]. Type-2 diabetes is characterized by the insulin resistance (IR) that results in decreased insulin sensitivity of skeletal muscle, liver and adipose tissue [3]. Physical inactivity and obesity also aggravates the chances of type-2 diabetes [4]. Generally, chronic efect of hyperglycemia may be cate- gorized into two major types of complications, namely, macrovascular and microvascular complications. The macrovascular complications include coronary artery disease (CAD) and peripheral arterial disease (PAD), while the microvascular complications include majorly neuro- pathy, nephropathy and retinopathy [3]. There are a number of anti- diabetic agents including sulphonylureas, thiazolidiones and various types of modulators of glucose-regulating enzymes such as α-glucosi- dase and dipeptidyl peptidase-4 [5]. Long term use of these agents show multiple adverse efects on the patient's body [6,7]. In this regard there is a consistent efort towards designing of anti-diabetic drugs that has ideally no side efect on the patients. Several herbal medicines are in use since ancient times in the pre- vention and cure of diseases [8]. The identifcation and isolation of herbal active pharmacological ingredients is based on many factors some of which include safety profle of the herb and its bioavailability. In this context, resveratrol (3,5,4 trihydroxystilbene), a phenolic phy- toalexin has emerged as a potential antioxidant that has anti-diabetic activity [9,10]. Resveratrol is mainly obtained from plant sources such as Polygonum cuspidatum [11] and Vitis vinifera [12]. In the French traditions, it has been a custom of consuming red wine along with high fat diet. The scientifc aspect of it suggests that red wine signifcantly reduces cardiovascular diseases (CVD) by overcoming excessive oxi- dative radicals that is generated from high fat diet [13,14]. In nature, resveratrol exits in two isoforms, namely the cis- and trans- isoforms (Fig. 1), however its biologically active form is trans isoform [15]. Since, resveratrol is principally an efective anti-oxidant, its molecular mechanism of action signifcantly revolves around oxidative stress re- lated pathways, however, other central signalling pathways are have also been reported to be altered by resveratrol at both translational and transcriptional level (Fig. 2). In vitro and In vivo studies of resveratrol have demonstrated its potential in the prevention and treatment of diabetes [16,17]. In the current review, we intend to focus on the po- tential use of resveratrol and its mechanism of action in attenuation of diabetes and diabetes related microvascular complications. https://doi.org/10.1016/j.lfs.2020.117350 Received 9 November 2019; Received in revised form 13 January 2020; Accepted 21 January 2020 ⁎ Corresponding author. E-mail addresses: hoda.muddasar@gmail.com, hoda@aliah.ac.in (M. Hoda). Life Sciences 245 (2020) 117350 Available online 23 January 2020 0024-3205/ © 2020 Elsevier Inc. All rights reserved. T Author's Personal Copy