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Natural supplements comprise good efficacy with less adverse effects as against diabetic therapy, but their advancement as anti-diabetic agents is unsatisfactory with regard to the delivery system. Dipeptidyl peptidase-4 (DPP4)/CD26) can degrade glucagon-like pepetide-1 (GLP-1) which renders a decrease of blood glucose levels. 16-hydroxycleroda-3,13-dine-16,15-olide (HCD) extracted from Polyalthia longifolia, exhibits numerous medicinal potentials including hypoglycemic potential. On consideration of HCD application, the bioavailability is affected by low solubility. Extended experiments of anti-diabetic efficacy confirmed HCD biocompatible with mesoporous silica nanoparticles (MSNs) encapsulation resulted in a sustained release property in delivering HCD for the inhibition of DPP4 via the activity and protein levels of DPP4 analysis. In the enzymatic activity assay, MSN-HCD directly changed DPP4 activity. Moreover, MSN-HCD nanoparticles were treated with Caco-2 cells and the protein levels of DPP4 determined within the cells. The results revealed that MSN-HCD caused reduction of DPP4 activity in a time- and dose-dependent fashion. Orally administered MSN-HCD in diet-induced diabetic mice alleviated blood glucose via an oral glucose tolerance test. In addition, administration of MSN-HCD for five weeks revealed that the biochemical cues such as pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), triglycerides (TG), cholesterol (CHO), and glycated hemoglobin (HbA1c) in mice were commendable as further confirmation of MSN-HCD efficacy and less adverse effects in down-regulation of hyperglycemia. Furthermore, this formulation effectively controlled blood glucose and significantly decreased the body weight of mice, suggesting that MSN-HCD exerts natural DPP4 inhibitor as a potential clinical drug for the treatment of diabetes.

nanomaterials

Encapsulation of 16-Hydroxycleroda-3,13-Dine-16,15-Olide in Mesoporous Silica Nanoparticles as a Natural Dipeptidyl Peptidase-4 Inhibitor Potentiated Hypoglycemia in Diabetic Mice