α-Glucosidase inhibitory effect of rhinacanthins-rich extract from Rhinacanthus nasutus leaf and synergistic effect in combination with acarbose

•Rhinacanthins-rich extract is a potent noncompetitive α-glucosidase inhibitor.•Rhinacanthins-rich extract and rhinacanthin-C show almost equal inhibitory activity.•Rhinacanthins-rich extract in combination with acarbose exert a synergistic effect.•In silico studies rationalized the inhibitory mechanism of rhinacanthin-C. Rhinacanthins-rich extract (RRE) from Rhinacanthus nasutus leaf and its marker compounds namely rhinacanthin-C, rhinacanthin-D and rhinacanthin-N were evaluated for α-glucosidase inhibitory activity. RRE (IC50 value of 25.0µg/mL) exhibited α-glucosidase inhibitory activity almost equivalent to that of rhinacanthin-C (IC50 value of 22.6µg/mL) but stronger than that of rhinacanthin-D (IC50 value of 71.5µg/mL) and the standard drug, acarbose (IC50 value of 395.4µg/mL), while rhinacanthin-N was inactive. Kinetic studies revealed that both RRE and rhinacanthin-C exhibited noncompetitive α-glucosidase inhibitory activity, while combinations of either RRE or rhinacanthin-C with acarbose at low concentrations (¼IC50, ½IC50 and IC50) showed a synergistic inhibitory effect. In silico studies identified the binding mode of rhinacanthin-C highlighting the formation of both polar and apolar contacts of ligand with α-glucosidase. The present study provides the first evidence that RRE containing rhinacanthin-C as the major compound, could find application as an α-glucosidase inhibitor.