Diabetes mellitus is a major global health concern in the current scenario which is chiefly characterized by the rise in blood sugar levels or hyperglycemia. In the context, DPP4 enzyme plays a critical role in glucose homeostasis. DPP4 targets and inactivates incretin hormones such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) as physiological substrates, which are essential to regulate the amount of insulin that is secreted after eating. Since the inactivation of incretins occurs, the hyperglycemic conditions continue to rise, and result in adverse physiological conditions linked with diabetes mellitus. Hence, inhibition of DPP4 has been the center of focus in the present antidiabetic studies. Although few DPP4 inhibitor drugs, such as alogliptin, saxagliptin, linagliptin, and sitagliptin, are available, their adverse effects on human metabolism are undeniable. Therefore, it becomes essential for the phytochemical intervention of the disease using computational methods prior to performing in vitro and in vivo studies. In this regard, we used an in-silico approach involving molecular docking, molecular dynamics simulations, and binding free energy calculations to investigate the inhibitory potential of Ocimum tenuiflorum phytocompounds against DPP4. In this regard, three phytocompounds (1S-α-pinene, β-pinene, and dehydro-p-cymene) from O. tenuiflorum have been discovered as the potential inhibitors of the DPP4 protein. To summarize, from our in-silico experiment outcomes, we propose dehydro-p-cymene as the potential lead inhibitor of DPP4 protein, thereby discovering new a phytocompound for the effective management of hyperglycemia and diabetes mellitus. The reported compound can be taken for in vitro and in vivo analyses in near future.

Medicinal formulations have evolved from the use of small molecules that act by blocking various receptors. On the contrary, therapeutic proteins are a class of medicines that have gained increased popularity owing to its low toxicity, high stability and exquisite specificity. Oral delivery of protein drugs is a very interesting but a highly challenging area of medicine that requires advancements in terms of bioavailability of oral drugs. The main objective of the present review is to provide a systematic overview of the various physiological barriers of delivery of therapeutic proteins and novel approaches available in this field in order to counter these physiological barriers. Advances in terms of inhibitors of proteases, permeation enhancers, mucoadhesives, short peptide conjugates, particulate delivery system including nanoparticles. Oral therapeutic proteins face challenges with regard to oral bioavailability, stability of the protein and reproducibility. Among the various strategies, a co-administration of permeation enhancers with protease inhibitors have proven most effective, while particulate delivery system is still under clinical studies in order to be establishes as a method. Overall, a thorough and focused research with sufficient knowledge on the structure-function relationship, substrate specificity and physiological parameters can deliver a potent therapeutic protein with high efficiency.