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Moringa oleifera Lam. (family; Moringaceae), commonly known as drumstick, have been used for centuries as a part of the Ayurvedic system for several diseases without having any scientific data. Demineralized water was used to prepare aqueous extract by maceration for 24 h and complete metabolic profiling was performed using GC-MS and HPLC. Hypoglycemic properties of extract have been tested on carbohydrate digesting enzyme activity, yeast cell uptake, muscle glucose uptake, and intestinal glucose absorption. Type 2 diabetes was induced by feeding high-fat diet (HFD) for 8 weeks and a single injection of streptozotocin (STZ, 45 mg/kg body weight, intraperitoneally) was used for the induction of type 1 diabetes. Aqueous extract of M. oleifera leaf was given orally at a dose of 100 mg/kg to STZ-induced rats and 200 mg/kg in HFD mice for 3 weeks after diabetes induction. Aqueous extract remarkably inhibited the activity of α-amylase and α-glucosidase and it displayed improved antioxidant capacity, glucose tolerance and rate of glucose uptake in yeast cell. In STZ-induced diabetic rats, it produces a maximum fall up to 47.86% in acute effect whereas, in chronic effect, it was 44.5% as compared to control. The fasting blood glucose, lipid profile, liver marker enzyme level were significantly (p < 0.05) restored in both HFD and STZ experimental model. Multivariate principal component analysis on polar and lipophilic metabolites revealed clear distinctions in the metabolite pattern in extract and in blood after its oral administration. Thus, the aqueous extract can be used as phytopharmaceuticals for the management of diabetes by using as adjuvants or alone.

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Design and development of potential pyruvate dehydrogenase kinase 3 (PDK3) inhibitors have gained attention because of their possible therapeutic uses in lung cancer therapy. In the present study, the binding affinity of naturally occurring alkaloids, hordenine, vincamine, tryptamine, cinchonine, and colcemid was measured with PDK3. The molecular docking and fluorescence binding studies suggested that all these compounds show a considerable binding affinity for PDK3. Among them, the affinity of hordenine to the PDK3 was excellent (K = 106 M−1) which was further complemented by isothermal titration calorimetric measurements. Hordenine binds in the active site pocket of PDK3 and forms a significant number of non-covalent interactions with functionally important residues. All-atom molecular dynamics (MD) simulation study suggested that the PDK3-hordenine complex is stabilized throughout the trajectory of 100ns and leads to fewer conformational changes. The enzyme inhibition studies showed that hordenine inhibits the activity of PDK3 with an IC50 value of 5.4 µM. Furthermore, hordenine showed a cytotoxic effect on human lung cancer cells (A549 and H1299) with an admirable IC50 value. However, it did not inhibit the growth of HEK293 cells up to 200 µM, indicating its non-toxicity to non-cancerous cell lines. In summary, our findings provide the basis for the therapeutic implication of hordenine and its derivatives in lung cancer and PDK3-related diseases after required in vivo validation.