Fabrication and Biological Assessment of Antidiabetic α-Mangostin Loaded Nanosponges: In Vitro, In Vivo, and In Silico Studies

Abstract

Type 2 diabetes mellitus has been a major health issue with increasing morbidity and mortality due to macrovascular and microvascular complications. The urgent need for improved methods to control hyperglycemic complications reiterates the development of innovative preventive and therapeutic treatment strategies. In this perspective, xanthone compounds in the pericarp of the mangosteen fruit, especially α-mangostin (MGN), have been recognized to restore damaged pancreatic β-cells for optimal insulin release. Therefore, taking advantage of the robust use of nanotechnology for targeted drug delivery, we herein report the preparation of MGN loaded nanosponges for anti-diabetic therapeutic applications. The nanosponges were prepared by quasi-emulsion solvent evaporation method. Physico-chemical characterization of formulated nanosponges with satisfactory outcomes was performed with Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Zeta potential, hydrodynamic diameter, entrapment efficiency, drug release properties, and stability studies at stress conditions were also tested. Molecular docking analysis revealed significant interactions of α-glucosidase and MGN in a protein-ligand complex. The maximum inhibition by nanosponges against α-glucosidase was observed to be 0.9352 ± 0.0856 µM, 3.11-fold higher than acarbose. In vivo studies were conducted on diabetic rats and plasma glucose levels were estimated by HPLC. Collectively, our findings suggest that MGN-loaded nanosponges may be beneficial in the treatment of diabetes since they prolong the antidiabetic response in plasma and improve patient compliance by slowly releasing MGN and requiring less frequent doses, respectively.

Anti-α-Glucosidase and Antiglycation Activities of α-Mangostin and New Xanthenone Derivatives: Enzymatic Kinetics and Mechanistic Insights through In Vitro Studies

“…With 0.05 µM α-glucosidase and 2 mM pNPG, the IC 50 of α-mangostin was 31.1 µM (pIC 50 = 4.51 ± 0.04), showing a higher affinity than acarbose, IC 50 = 1712 µM (pIC 50 = 2.77±0.04), tested as a positive control, resulting in an inhibitory potency ratio of 55. Other authors reported the α-mangostin inhibition on α-glucosidase, showing IC 50 values ranging from 1.3 to 29.3 µM [11][12][13]33,34]; among these investigations, only three compared the inhibition with that of acarbose, evidencing a potency ratio of 2.1, 8.2 and 18.8 [11,13,34].…”

“…α-Mangostin is a 9H-xanthene-9-one derivative mainly isolated from the fruit of Garcinia mangostana L. (Clusiaceae family), commonly known as mangosteen, a plant widely cultivated in Southeast Asian countries [8][9][10]. Studies have shown that the plant-derived α-mangostin possesses several pharmacological properties, including anti-inflammatory, antidiabetic, cardioprotective, and antimicrobial activities [10][11][12][13][14]. α-Mangostin and related xanthones are generally considered safe and well tolerated in vivo [15,16].…”

Designing Next-Generation Drug-like Molecules for Medicinal Applications

“…Various physicochemical properties, including the zeta potential, entrapment efficiency, hydrodynamic diameter, and drug-release properties were also tested. The in vitro α -glucosidase inhibition potential demonstrated appreciable results, which were reinforced with in vivo studies [ 7 ].…”

Role of Neuropilin 1 in COVID-19 Patients with Acute Ischemic Stroke

“…Furthermore, various metabolic disorders are associated with the reduction of soluble NRP-1(sNRP-1), which has protective effects against AngII-induced inflammation [ 112 , 113 ]. In addition, sNRP-1 is up-regulated in HIV-positive pregnant women due to mimicry with VEGF or integrin, which mediate angiogenesis via NRP-1 receptors [ 114 ].…”