Type 2 diabetes (T2D) is characterized by insufficient insulin secretion by the pancreatic beta cells and insulin resistance in liver, skeletal muscle, and white adipose tissue. Adipose tissue plays a major role in glucose homeostasis and lipid metabolism. Dietary antioxidants such as resveratrol and mangiferin may offer some protection against the early stage of diabetes mellitus. Therefore, an attempt has been made to investigate the effects of resveratrol and mangiferin on biochemical parameters and molecular mechanism of PPARγ and FALDH gene expression in adipose tissue of streptozotocin- (STZ-) nicotinamide- (NA-) induced diabetic rats. Albino Wister rats were randomly divided into five groups: control rats (Group 1), diabetic control rats (Group 2), diabetic rats given resveratrol (40 mg/kg body weight per day; Group 3), diabetic rats given mangiferin (40 mg/kg body weight per day; Group 4), diabetic rats given glibenclamide (0.6 mg/kg body weight per day; Group 5). Serum biochemical parameters-total cholesterol (TC), total triglyceride (TG), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, glycosylated hemoglobin (HbA1c), urea, and uric acid were analyzed. We found that the oral administration of resveratrol and mangiferin to STZ-NA-induced diabetic rats for 30 days showed the significant protective effect on all the biochemical parameters. A significant reduction in blood glucose and HbA1c levels was observed in rats treated with 40 mg/kg body weight per day of resveratrol or mangiferin. Moreover, both these antioxidants showed significant enhancement of PPARγ and FALDH gene expression in rat adipose tissue compared to control rats.

Protein kinases (PKs) present in Plasmodium falciparum catalyze phosphorylation reaction to control growth and differentiation of the parasite throughout the life cycle. Protein kinase inhibitors are found to kill the parasite but their cellular target enzymes are not known. Protein kinase inhibitors are evaluated in an in sillico docking studies using plasmodium falciparum RIO-2 kinase (right open reading frame-2 protein kinase) as target enzyme. Most of the protein kinase inhibitors showed appropriate docking within the ATP binding domain of the PfRIO-2 kinase. The initial docking experiments were further validated by a substrate competition experiment to validate the preliminary screening results and test the potentials of these inhibitors under in vivo conditions. Docking and substrate competition study identifies wortmannin, enzastaurin, indirubin-3'-monoxime, apigenin, kaempferol and 8-hydroxy-4-methyl-9-nitro-2H-benzo[g]chromen-2-one as lead inhibitors against native/active form of the PfRIO-2 kinase. The top protein kinase inhibitors bind into the ATP binding site with a similar conformation as ATP. The docking result is in good agreement with the antimalarial schizonticidal IC50 (μg/ml) of an inhibitor and gives a correlation factor (R2) of 0.82 whereas top hit antimalarial inhibitors gives a correlation factor (R2) of 0.99. In summary, our work highlights the importance of PfRIO-2 kinase as a target behind the antimalarial action of protein kinase inhibitors and might help to design a new set of antimalarial remedies.

As the prevalence of type 2 diabetes (T2D) is rapidly increasing, and effective strategies to manage and prevent this disease are urgently required, as per WHO statistics undertaken in 2012, the number of people suffering from T2D in India is expected to shoot up from 40.9 million in 2007 to 69.9 million by the year 2025. Even though, the symptoms of T2D are seen in the later stages of life, the onset of the disease occurs quite early and is referred to as lifestyle disorder. Insulin resistance and β cell dysfunction are the main causative factors along with mutations in the genes regulating glucose homeostasis and β cell development. A vicious circle of the causes and effects of hyperglycemia interlinked together forms the whole picture of T2D. Our review discusses the molecular targets of the current oral therapeutic drugs, which cuts down hyperglycemia. This review aims to provide better insights to comprehension of the disease, recent advances in molecular and cellular therapies. A comprehensive analysis of these novel targets identified over the years and various therapeutic leads which successfully completed their clinical trials are presented in this review. Few of these lead molecules operate as GLP-1 agonist, SGLT2 inhibitors, and DPP-IV inhibitors and are termed as next generation anti-diabetic drugs.

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