Diabetes mellitus (DM) is a metabolic disease characterized by high levels of blood glucose resulting from low insulin production and uptake.Non-traditional treatment of diabetes from medicinal plants showed potential antidiabetic activity.Cissus rotundifolia (family, Vitaceae) is known plant in southwestern part of Saudi Arabia and used by people in the region to treat skin diseases, burns, and diabetes. Chemical and biological characteristics of Cissus rotundifolia active compounds are unknown.The aim of this study to investigate the chemical and biological properties of this medicinal plant using bio-assay guided separation.Aqueous methanol extract of Cissus rotundifolia was fractionated by partitioning against hexane and ethyl acetate.Methanol, ethyl acetate and hexane extracts are screened for antidiabetics activity using alpha-glycosidase assay at concentration of 12.5-50 mg/ml.Methanol extract showed a significant alpha-glucosidase inhibition percent of 58 % to 95%. Further LC separation afforded six compounds 1- 6 isolated and characterized using 1H-NMR, 13C-NMR and 2D-NMR. Compound 3 (Butanedioic acid, 2-hydroxyl, 1-methyl ester) and compound 4 (4-methyl 1-vinyl 2-hydroxysuccinate) are identified the main constituent of methanol extract and showed a significant inhibition of alpha-glycosidase enzyme in range of 65% to 50% at concentration range from 1.00 – 0.25 mg/ml. The two isolated compounds identified with dicarboxylic group and hydroxyl group with similarity to malate structure (one of the main intermediates of citric acid cycle).This lead us to build hypothesis that investigation of the ability of the isolated compounds to inhibit gluconeogenesis process through inhibition of the citric acid cycle that consider one of the main pathway to reduce the blood glucose level. Molecular docking study of the isolated compounds binding affinity to citric acid cycle enzymes was conducted.The docking results showed that butanedioic acid, 2-hydroxy-, 1-methyl ester has a significant consensuses scores with high affinity binding to succinate dehydrogenase and citrate synthetase enzymes that play an important role in citric acid cycle.Isolated compounds showed inhibition of intestinal α-glucosidase enzyme and binding affinity to citric acid cycle enzymes indicate potential antidiabetic properties that may decrease of hepatic glucose by decreasing gluconeogenesis.The docking result and antidiabetic activity of alpha-glucosidase inhibition will be presented.

Anti-diabetic activity of Cissus rotundifolia plant growing in Saudi Arabia

2019 Spring National Meeting

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