Suresh Kumar Gupta

Curcumin prevents experimental diabetic retinopathy in rats through its hypoglycemic, antioxidant, and anti-inflammatory mechanisms.

PURPOSE The purpose of this study was to evaluate the therapeutic potential of oral curcumin (1 g/kg body weight of rat) in the prevention and treatment of streptozotocin-induced diabetic retinopathy in Wistar albino rats. METHODS The treatment was carried out for a period of 16 weeks in diabetic rats and evaluated for hyperglycemic, antioxidant (superoxide dismutase, catalase, and glutathione), and inflammatory parameters (tumor necrosis factor-α, vascular endothelial growth factor). Rat fundus was observed weekly to see any visible changes in the retina, such as tortuosity and dilation of retinal vessels. Histological changes were evaluated by transmission electron microscopy. RESULTS Treatment with curcumin showed significant hypoglycemic activity compared with the diabetic group. Retinal glutathione levels were decreased by 1.5-fold, and antioxidant enzymes, superoxide dismutase and catalase, showed >2-fold decrease in activity in the diabetic group; on the other hand, curcumin positively modulated the antioxidant system. Proinflammatory cytokines, tumor necrosis factor-α and vascular endothelial growth factor, were elevated >2-fold in the diabetic retinae, but prevented by curcumin. Transmission electron microscopy showed degeneration of endothelial cell organelles and increase in capillary basement membrane thickness in diabetic retina, but curcumin prevented the structural degeneration and increase in capillary basement membrane thickness in the diabetic rat retinae. CONCLUSION Based on the above results, it may be concluded that curcumin may have potential benefits in the prevention of retinopathy in diabetic patients.

Clinical biomarkers and molecular basis for optimized treatment of diabetic retinopathy: current status and future prospects

Diabetic retinopathy is a highly specific microvascular complication of diabetes and a leading cause of blindness worldwide. It is triggered by hyperglycemia which causes increased oxidative stress leading to an adaptive inflammatory assault to the neuroretinal tissue and microvasculature. Prolonged hyperglycemia causes increased polyol pathway flux, increased formation of advanced glycation end-products, abnormal activation of signaling cascades such as activation of protein kinase C (PKC) pathway, increased hexosamine pathway flux, and peripheral nerve damage. All these changes lead to increased oxidative stress and inflammatory assault to the retina resulting in structural and functional changes. In addition, neuroretinal alterations affect diabetes progression. The most effective way to manage diabetic retinopathy is by primary prevention such as hyperglycemia control. While the current mainstay for the management of severe and proliferative diabetic retinopathy is laser photocoagulation, its role is diminishing with the development of newer drugs including corticosteroids, antioxidants, and antiangiogenic and anti-VEGF agents which work as an adjunct to laser therapy or independently. The current pharmacotherapy of diabetic retinopathy is incomplete as a sole treatment option in view of limited efficacy and short-term effect. There is a definite clinical need to develop new pharmacological therapies for diabetic retinopathy, particularly ones which would be effective through the oral route and help recover lost vision. The increasing understanding of the mechanisms of diabetic retinopathy and its biomarkers is likely to help generate better and more effective medications.

Medicinal Herbs can Play Significant Role in Attenuation of Ischemia and Reperfusion Injury

Nature has been a source of medicinal treatments for thousands of years and plant-derived products continue to play an essential role in the primary health care of about 80-85% of the world’s population. Medicinal herbs are widely used in Ayurveda, the Indian System of Medicine and have been observed to possess numerous activities with regard to cardiovascular system viz. antiplatelet, hypolipidemic, anti-inflammatory, hypoglycemic and hypotensive actions. Hence, these herbal extracts traditionally used have been evaluated scientifically in the present study with an aim to define the role of these agents in limiting the deleterious effects of myocardial ischemia and reperfusion (IR) injury by providing scientific data to validate their use as prophylactic approaches or as an adjunct to standard treatment (synthetic compounds employed in conventional treatment protocols) of ischemic heart disease. The efficacy of Withania somnifera (Ws), Curcuma longa (Cl) and Ocimum sanctum (Os), and herbal combination (HCB) including {Ws (50 mg/kg) + Cl (100 mg/kg) + Os (75 mg/kg} to limit injury in the setting of myocardial ischemia and reperfusion was explored in the present study. An open chest left anterior descending coronary artery (LAD) occlusion and reperfusion induced myocardial injury was used as the experimental model. Wistar albino rats were divided into ten groups and orally fed saline once daily (sham, control IR) or medicinal herbs (Ws/Cl/Os/HCB; Ws-IR, Cl-IR/Os-IR/HCB-IR) respectively for 1 month. On the 31st day in the rats of the Control IR and Ws-IR, Cl-IR/Os-IR/HCB-IR groups, LAD was occluded for 45 min, and reperfused for 1 h. Hemodynamic parameters were recorded at preset points and subsequently sacrificed for biochemical, immunohistochemical and pathological studies. In the control IR group, significant ventricular dysfunction, cardiac necrosis, apoptosis; decline in antioxidant status and elevation in lipid peroxidation was observed. Chronic oral treatment with HCB per se for 1 month resulted in significant enhancement of the myocardial endogenous antioxidant enzymes. Pretreatment with Ws, Cl and the herbal combination exerted significant cardioprotective effects in the experimental model of myocardial injury. The most remarkable observation of the present study was that cardioprotective effect exerted by HCB treatment was found to be superior to that shown by singular treatment with individual herbal extracts. The combination of herbal extracts was found to significantly ameliorate the ischemia and reperfusion cardiomyocyte apoptosis, cardiac dysfunction, compromised antioxidant status and histopathologic alterations as compared to control IR group. Cardioprotection by HCB treatment may be attributed to its favorable hemodynamic effects, myocardial adaptogenic properties, and significant antioxidant and antiapoptotic properties. Furthermore, HCB decreased the severity of pathological changes and significantly preserved the myocardial creatinine phosphokinase confirming its myocardial salvaging effects. Results clearly demonstrated the therapeutic potential of the herbal drugs in the treatment of myocardial ischemia and reperfusion injury. If the beneficial effects can be established in-patients, these findings may represent a novel adjunctive therapy of ischemic heart disease and Myocardial Infarction.

Ocular Pharmacology and Therapeutics: Origin, Principle, Challenges, and Practices

Recent revelations on the origin of eye specific applications bring out the fascinating history from various civilizations. Use of black kohl eyeliner and the possible science behind it has been explored through contemporary technology.Chemical analysis of the contents of the pyxis recovered from the Roman vessel that was shipwrecked off the coast of Tuscany more than 2000 years ago, showed thepresence of higher amounts of zincwhich might have been used to treat eye infections. Literatures available from ancient civilizations indicate the use of many INTERESTING drug formulations for the eye. This chapter narrates the history for such usage attributing to the development of medications for ocular therapeutics, principles of ocular therapy and challenges in applying ocular pharmacology to therapeutics.