Study on α-Glucosidase Inhibitors from Solanum stramonifolium Jacq. Inflorescence and Neuropeltis racemosa Wall. Stem

Abstract

This research was the first report, which studied on the phytochemical investigation and potential anti-diabetic effect of two plants from order Solanales, Solanum stramonifolium Jacq. inflorescence and Neuropeltis racemosa Wall. stem. The plant extracts were evaluated the α-glucosidase inhibitory activity. The ethyl acetate extract of S. stramonifolium (SSEA) inflorescence and the ethanol extract of N. racemosa (NREO) stem showed better inhibitory activity than other solvent extracts with IC50 215.92 and 39.65 μg/ml, respectively. Both of these extracts performed mixed-type inhibition. The combination study of extracts with acarbose standard suggested that SSEA and NREO extracts promoted the activity of acarbose to inhibit the α-glucosidase enzyme. The isolation used the α-glucosidase inhibitory activity guided fractionation. Ten compounds and one mixture compound were obtained. The five compounds and a mixture compound from S. stramonifolium were identified as flavonoid compounds that were myricetin 3, 4, 5, 7-tetramethyl ether (SS1), combretol (SS2), kaempferol (SS3), kaempferol-7-O--glucopyranoside (SS4), 5-hydroxy3, 7, 4, 5 -tetramethoxyflavone-3-O-glucopyranoside (SS5), and a mixture (SS6) of isorhamnetin-3-O-glucopyranoside (SS6-1) and kaempferol-3-O-glucopyranoside (SS6-2). Other five compounds from N. racemosa were defined as scopoletin (NR1), syringic acid (NR2), methyl 3-methyl-2-butenonoate (NR3), trans-N-feruloyltyramine (NR4) and trans-N-coumaroyltyramine (NR5). From previous survey, the compound of SS5 has not been reported before. The isolated flavonoid compounds of S. stramonifolium were obtained small amount. So, they were preformed the α-glucosidase inhibitory activity as the percent of inhibition. Kaempferol and kaempferol-3-O-glucopyranoside (astragalin) were used as the representative compounds for the study on mechanism of action and enzyme inhibition of the combination with acarbose. Both of kaempferol and astragalin performed mixed-type inhibition with α-glucosidase. Additionally, α-glucosidase inhibitory acitvity of acarbose was decreased when combined with kaempferol or astragalin. The compound NR1, NR2, NR3, NR4 and NR5 of N. racemosa showed α-glucosidase inhibitory acitvity with IC50 as 577.46, >2,523.09, >4,380.59, 95.34 and 3.25 μM, respectively, whereas the acarbose presented IC50 as 424.40 μM. The mechanism of action analysis exhibited that NR1 displayed mixed-type inhibition manner, while NR4 and NR5 exhibited uncompetitive inhibition manner with Ki 51.81 and 1.99 μM, respectively. Moreover, the molecular docking study provided the understanding to α-glucosidase inhibition of isolated compounds. For the flavonoid compounds from S. stramonifolium, the non-glycosylated flavonoids (SS2 and SS3) showed lower binding energy than their glycosylated flavonoid derivatives (SS4, SS5 and SS6-2). The binding energy of SS2 showed -3.53 Kcal/mol, while SS5 was 63.78 Kcal/mol. SS3 exhibited the binding energy as -3.02 Kcal/mol, while SS4 and SS6-2 were -1.29 and 55.47 Kcal/mol, respectively. So, non-glycosylated flavonoids exhibited better α-glucosidase inhibitory activity than glycosylated flavonoid derivatives. For the isolated tyramine-derived amides from N. racemosa, the binding energy of NR4 and NR5 were -5.42 and -5.15 Kcal/mol, respectively. Both of NR4 and NR5 demonstraded the potential to α-glucosidase inhibition. Fortunately, these findings could be used to relate the accordance between the laboratory and the computer experiments. These results will be the beneficial informations for the furture drug discovery.