Natural Triterpenoids Isolated from Akebia trifoliata Stem Explants Exert a Hypoglycemic Effect via α-Glucosidase Inhibition and Glucose Uptake Stimulation in Insulin-Resistant HepG2 Cells.

The inhibition of α-glucosidase activity is a prospective approach to attenuate postprandial hyperglycemia in the treatment of type 2 diabetes mellitus (T2DM). Herein, the inhibition of α-glucosidase by three compounds T1 -T3 of Akebia trifoliata stem, namely hederagenin (T1 ), 3-epiakebonoic acid (T2 ), and arjunolic acid (T3 ) were investigated using enzyme kinetics and molecular docking analysis. The three triterpenoids exhibited excellent inhibitory activities against α-glucosidase. T1 -T3 showed the strongest inhibition with IC50 values of 42.1±5.4, 19.6±3.2, and 11.2±2.3 µM, respectively, compared to the acarbose positive control (IC50 =106.3±8.2). Enzyme inhibition kinetics showed that triterpenoids T1 -T3 demonstrated competitive, mixed, and noncompetitive-type inhibition against α-glucosidase, respectively. The inhibition constant (Ki ) values were 21.21, 7.70, and 3.18 µM, respectively. Docking analysis determined that the interaction of ligands T1 -T3 and α-glucosidase was mainly forced by hydrogen bonds and hydrophobic interactions, which could result in improved binding to the active site of the target enzyme. The insulin resistant (IR)-HepG2 cell model used in this study (HepG2 cells exposed to 10-7  M insulin for 24 h) and glucose uptake assays showed that compounds T1 -T3 had no cytotoxicity with concentrations ranging from 6.25 to 25 µM and displayed significant stimulation of glucose uptake in IR-HepG2 cells. Thus, triterpenoids T1 -T3 showed dual therapeutic effects of α-glucosidase inhibition and glucose uptake stimulation and could be used as potential medicinal resources to investigate new antidiabetic agents for the prevention or treatment of diabetes.

Structure characterization and immunomodulatory activity of a new neutral polysaccharide SMP-0b from Solanum muricatum.

In the present study, a novel neutral polysaccharide SMP-0b was extracted and purified from the pulp of Solanum muricatum. Monosaccharide composition analysis revealed that SMP-0b was mainly composed of l-arabinose, d-mannose, d-glucose and d-galactose with the molar ratio of 5.31:2.92:42.23:25.38. The weight-average molecular weight and number-average molecular weight of SMP-0b was calculated to be 13.51 kDa and 9.91 kDa respectively through high performance gel permeation chromatography. The structure of SMP-0b was characterized by methylation and NMR analysis. It showed that the backbone chain of SMP-0b was consisted of →4)-ß-d-Galp-(1→, →3,6)-ß-d-Manp-(1→ and →6)-α-d-Glcp-(1→, and the side chain was composed of α-l-Araf-(1→ and →4)-α-d-Glcp-(1→. In immunomodulation assays in vitro, SMP-0b exhibited good immunomodulatory activity and could significantly stimulate proliferation and NO production of RAW 264.7 macrophage cells. The results suggested that the neutral polysaccharide from Solanum muricatum might have potential as an immunomodulator or supplement in functional food to enhance immunity.