Malaria is one of the most devastating infectious diseases that caused millions of clinical cases annually despite decades of prevention efforts. Recent cases of Plasmodium falciparum resistance against the only remaining class of effective antimalarial (artemisinin) in South East Asia may soon pose a significant threat. Hence, the identification of new antimalarial compounds with a novel mode of action is necessary to curb this problem. Protein kinase has been implicated as a valid target for drug development in diseases such as cancer and diabetes in humans. A similar approach is now recognized for the treatment of protozoan-related disease including malaria. Few Plasmodium protein kinases that are not only crucial for their survival but also have unique structural features have been identified as a potential target for drug development. In this review, studies on antimalarial drug development exploiting the size of Plasmodium protein kinase ATP gatekeeper over the past 15 years are mainly discussed. The ATP-binding site of Plasmodium protein kinases such as Pf CDPK1, Pf CDPK4, Pf PKG, Pf PK7, and Pf PI4K showed great potential for selective and multi-target inhibitions owing to their smaller or unique ATP-gatekeeper amino acid subunits compared to that of human protein kinase. Hence it is a feasible solution to identify a new class of active antimalarial agents with a novel mode of action and longer clinical life-span.

Objective: To evaluate the antidiabetic potential of leaf extracts of Tylophora hirsuta (T. hirsuta). Methods: The methanolic and ethyl acetate extracts of T. hirsuta leaves were analyzed by high pressure liquid chromatography. In vitro antioxidant activity was determined by ferric ion reduction, 1, 1-diphenyl-2-picrylhydrazyl, and hydrogen peroxide scavenging methods. In vitro alpha amylase (α-Amylase) inhibitory activity of the plant extracts was assessed. In vivo antidiabetic potential was determined in alloxan-induced diabetic mice to assess glycated hemoglobin (HbA1c), oral glucose tolerance, serum amylase, lipid profile, fasting blood glucose, and body weight. Histopathological lesions of the pancreas, liver and kidney were observed. Oxidative stress biomarkers such as superoxide dismutase, catalase and peroxidase were also determined. Results: Quercetin, chlorogenic acid, p-coumaric acid, and m-coumaric acid were found in the plant extracts. The methanolic plant extract exhibited higher in vitro antioxidant activities than the ethyl acetate extract. Moreover, methanolic plant extract exhibited (83.90±1.56)% α-Amylase inhibitory activity at 3.2 mg/ mL concentration. Animal study showed that the methanolic extract of T. hirsuta improved the levels of fasting blood glucose, HbA1c, serum α-Amylase, lipid profile, liver function biomarkers, and kidney functions of diabetic mice. Moreover, the methanolic extract ameliorated diabetes-related oxidative stress by increasing superoxide dismutase and catalase activities and decreasing peroxidase and malondialdehyde levels. Histopathological examination showed that the plant extract had improved the integrity of pancreatic islets of Langerhans and reduced the pathological lesions in the liver and kidney of diabetic mice. Conclusions: The methanolic extract of T. hirsuta exhibits pronounced antidiabetic activity in mice through reduction of oxidative stress. The plant extract has several natural antioxidants such as phenolic acids. T. hirsuta extract could serve as a nutraceutical for managing diabetes mellitus.