Glucokinase activators are considered as new therapeutic arsenals that bind to the allosteric activator sites of glucokinase enzymes, thereby maximizing its catalytic rate and increasing its affinity to glucose. This study was designed to identify potent glucokinase activators from prenylated flavonoids isolated from medicinal plants using molecular docking, molecular dynamics simulation, density functional theory, and ADMET analysis. Virtual screening was carried out on glucokinase enzymes using 221 naturally occurring prenylated flavonoids, followed by molecular dynamics simulation (100 ns), density functional theory (B3LYP model), and ADMET (admeSar 2 online server) studies. The result obtained from the virtual screening with the glucokinase revealed arcommunol B (−10.1 kcal/mol), kuwanon S (−9.6 kcal/mol), manuifolin H (−9.5 kcal/mol), and kuwanon F (−9.4 kcal/mol) as the top-ranked molecules. Additionally, the molecular dynamics simulation and MM/GBSA calculations showed that the hit molecules were stable at the active site of the glucokinase enzyme. Furthermore, the DFT and ADMET studies revealed the hit molecules as potential glucokinase activators and drug-like candidates. Our findings suggested further evaluation of the top-ranked prenylated flavonoids for their in vitro and in vivo glucokinase activating potentials.
This study investigated the anti-diabetic activity of the root bark extract of Parquetina nigrescens and the isolated compound, convallatoxin, from the root bark. A powdered sample of the plant was extracted with methanol, and the extract (A) was tested in glucose-loaded normal rats at 100, 200 and 400 mg/kg for the determination of the most active dose. The anti-diabetic activity of A at 200 mg/kg was carried out on streptozotocin-induced diabetic rats. A was further partitioned to obtain its n-hexane (B 1 ), dichloromethane (B 2 ), ethyl acetate (B 3 ) and mother liquor (B 4 ) fractions that were tested for blood glucose lowering activity using glucose-loaded normal rats model. The anti-
Diabetes mellitus is a life-threatening non-communicable disease that affects all age groups. Despite the increased attention it has received in recent years, the number of diabetic patients has grown exponentially. These increased cases are attributed to essential enzymes involved in blood glucose regulation. In this study, we attempt to reveal the aldose reductase inhibitory potential of xanthones isolated from African medicinal plants. Ensemble docking, molecular dynamics simulation, density functional theory (DFT), and ADMET methods were employed to identify drug candidates as aldose reductase inhibitors. The ensemble docking results identified mangostenone B, bangangxanthone A, smeathxanthone B, mangostenone A, and allanxanthone B as potent inhibitors against the aldose reductase enzyme. Molecular dynamics studies showed the xanthones established better binding mode and affinities against the enzyme. Moreover, the electronic properties of the xanthones explained their good pharmacological potentials. Therefore, our findings suggest that the hit molecules be investigated in vitro and in vivo for drug development against aldose reductase.
Leaves of Olax subscorpioidea, Hoslundia opposita, Cleistopholis patens, Plumbago zeylanica and Dioscoreophyllum cumminsii that are used as anti-diabetics were evaluated for hyperglycaemic-lowering and antioxidant activities to justify their Nigerian ethnomedicinal usage. Leaf methanolic extracts (100, 200 and 400 mg/kg, p.o.) were assayed in normal, glucose- and alloxan-induced diabetic rats, while 1,1,-diphenyl-2-picrylhydrazyl, total antioxidant capacity, ferric reducing antioxidant power and hydroxyl radical scavenging tests were used for their antioxidant activity. Effects of n-hexane, dichloromethane, ethylacetate and aqueous partition fractions of the three most active anti-hyperglycaemic extracts were also tested in glucose-loaded rats. In normoglycaemic rats, all extracts generally lacked activity, while with glucose-loaded rats, only O. subscorpioidea (200mg/kg) and C. patens (400 mg/kg) at 1 h and O. subscorpioidea (200, 400 mg/kg) and C. patens (400 mg/kg) at 2-4 hours gave lowered (p < 0.05) blood glucose levels than glibenclamide (5 mg/kg), while activity of H. opposita and P. zeylanica (200 mg/kg) were only comparable to glibenclamide. When daily fed for fourteen days to alloxan-induced diabetic rats, all extracts, at their most active doses, gave significantly higher activity than glibenclamide. Olax subscorpioidea leaf extract had the highest hyperglycaemic-lowering and least antioxidant activities. Highest antioxidant activity of H. opposita may suggest some contribution of antioxidant property to its hyperglycaemic-lowering activity. The glucose-lowering and insulinotropic constituents of O. subscorpioidea, H. opposita and C. patens should be concentrated in their aqueous, aqueous and dichloromethane fractions, respectively. Anti-hyperglycaemic ethnomedicinal use of these plants was justified and H. opposita has additional antioxidant property. Keywords: Antioxidant activity; Diabetes mellitus; Nigerian anti-diabetic plants
This study was planned and executed to validate the anti-diabetic ethno-medicinal claim of Caesalpinia pulcherrima (Fabaceae) pods and the isolation of potential chemical compounds responsible for the activity.The anti-diabetic activity of the extract was assayed using oral glucose tolerance test and streptozotocin induced hyperglycaemic rats. The partition fractions of the extract were evaluated for their anti-hyperglycaemic activity using oral glucose tolerance test. The most active fraction was subjected to chromatographic separations that led to the isolation and characterisation of two new polyphenolic compounds. The structures of these compounds were elucidated and characterized using IR, 1D- and 2D-NMR and MS techniques.The extract gave comparable (p>0.05) activity to glibenclamide (5 mg/kg) at 100, 200 and 400 mg/kg at 4 h in oral glucose tolerance test and streptozotocin induced diabetic model on day 21. The most active ethyl acetate fraction (200 mg/kg) elicited comparable activity to the positive control at 0.5-4 h with blood glucose reduction of 52.9 % as compared with glibenclamide (5 mg/kg) of 38.9 % at 4 h. The isolated compounds were identified to be 5-(4-hydroxyphenyl)-3-hydroxy-2-methoxyphenol and 3-(4-methanetriol-2,6-dihydroxyphenyl)-3',4',5',5,7-pentahydroxyflavanonol.The significant anti-diabetic property shown by the pods of C. pulcherrima justified its anti-diabetic ethno-medicinal use and the two new polyphenolic compounds isolated from its most active fraction could have contributed to the observed activity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.