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Chemical Group Profiling, In Vitro and In Silico Evaluation of Aristolochia ringens on α-Amylase and α-Glucosidase Activity.

ABSTRACT: Diabetes mellitus (DM) has become a global scourge, and there is a continuous search for novel compounds as viable alternatives to synthetic drugs which are often accompanied by severe adverse effects. Aristolochia ringens is among the scientifically implicated botanicals effective in the management of several degenerative diseases including DM. The current study evaluated the inhibitory mechanism(s) of root extract of A. ringens on α-amylase and α-glucosidase in vitro and in silico, while its constituents were characterized using liquid chromatography-mass spectrometric technique. The extract had concentration-dependent inhibitory effect on the study enzymes, and the inhibition compared well with that of standard drug (acarbose) with respective IC₅₀ values of 0.67 mg/mL (α-amylase) and 0.57 mg/mL (α-glucosidase) compared with that of the extract (0.63 and 0.54 mg/mL). The extract competitively and uncompetitively inhibited α-amylase and α-glucosidase, respectively. Of the identified compounds, dianoside G (-12.4, -12.5 kcal/mol) and trilobine (-10.0, -10.0 kcal/mol) had significant interactions with α-amylase and α-glucosidase, respectively, while magnoflorine and asiatic acid also interacted keenly with both enzymes, with quercetin 3-O-glucuronide and strictosidine showing better affinity towards α-glucosidase. These observations are suggestive of involvement of these compounds as probable ligands contributing to antidiabetic potential of the extract. While studies are underway to demystify the yet to be identified compounds in the extract, the data presented have lent scientific credence to the acclaimed in vivo antidiabetic potential of the extract and suggested it as a viable source of oral hypoglycaemic agent.

SUBMITTER: Ahmad JB

PROVIDER: S-EPMC8203400 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAs a traditional herbal medicine, Dracaena angustifolia Roxb has been used as an anti-inflammatory agent by the Li people in Hainan, China. In preliminary phytochemical studies conducted in our lab, its fractions were found to inhibit α-glucosidase in vitro, indicating a potential for alleviating glucose dysregulation.MethodsThrough in vitro enzymatic assays, the abilities of the separated components to affect α-glucosidase and α-amylase were evaluated. By establishing concentration gradients and generating Lineweaver-Burk plots, the corresponding inhibition modes together with kinetic parameters were assessed. Following the evaluation of the outcomes of their combination with acarbose, computational docking and molecular dynamic simulations were carried out to analyse the interaction mechanisms and perform virtual screening against human enzymes.ResultsCompared with acarbose, 7 compounds, including flavonoid derivatives, amides and aromatic derivatives, with higher α-glucosidase inhibitory efficiencies were confirmed. It was found that those competitive/mixed candidates and acarbose interacted synergistically or additively on α-glucosidase. Moreover, 3 of them were able to inhibit α-amylase in mixed mode, and additive effects were observed in combination with acarbose. Through in silico docking, it was found that the active site residues as well as adjacent residues were involved in α-glucosidase and α-amylase binding, which were mainly achieved through hydrogen bonding. Among those dual-function flavonoids, Compound 9 was predicted to be a considerable inhibitor of human enzymes, as the formation of ligand-enzyme complexes was mediated by the residues responsible for substrate recognition and catalysis, the stabilities of which were reiterated by molecular dynamics simulations.ConclusionDespite their mild effects on α-amylase, considerable α-glucosidase inhibitory efficiencies and potential synergy with acarbose were exhibited by these natural candidates. Furthermore, a stable ligand, human α-glucosidase, was predicted by the performed simulations, which provided useful information for the application of Dracaena angustifolia Roxb in diabetes treatment.

Project description:Hyperglycemia is the hallmark of type 2 diabetes mellitus, and its prevention will go a long way in managing the disease and its associated complications. Reduction of postprandial hyperglycemia through retarding carbohydrates digesting enzymes is one of the major therapeutic approaches used in the management of diabetes.The aim of the present study was to investigate the antidiabetic and cytotoxic effects of Cissus cornifolia extracts in vitro.The α-amylase and α-glucosidase inhibitory activities of ethanolic and aqueous extracts of C. cornifolia root and leaves were investigated when the cytotoxic effects of these extracts were analyzed using MTT assay on human embryonic kidney (HEK 293) cell lines.The root ethanolic extract showed a mild α-amylase inhibitory activity with IC50 value of 22.75 ± 1.23 μg/ml, but strong α-glucosidase inhibitory activity with IC50 value 2.81 ± 0.97 μg/ml and the aqueous root extract indicated moderate inhibition for both α-amylase and α-glucosidase with IC50 values of 33.70 ± 3.75 and 37.48 ± 2.35 μg/ml, respectively. The ethanolic root extract was found nontoxic at tested concentrations on HEK 293 cell lines as confirmed by the MTT assay with 93% cell viability at the highest concentration (200 μg/ml) tested. However, the aqueous extracts (leaf and root) were found cytotoxic at concentrations above 50 μg/ml.Data of this study suggest that the root ethanolic extracts of C. cornifolia possesses moderate α-amylase, but strong α-glucosidase inhibitory activity in vitro and did not show significant cytotoxicity with the tested concentrations.Present study was conducted to examine effects of antidiabetic and cyctotoxic effects of Cissus conrnifolia root and leaves extracts in vitro. Data of this study suggest that the root ethanolic extract of C. cornifolia possesses mild to moderated antidiabetic activity via inhibiting carbohydrate digesting enzymes when no significant toxicity was observed with tested concentrations. Abbreviations used: alex: Aqueous leaf extract; arex: Aqueous root extract; CC: Cissus cornifolia; DNS: Dinitrosalicylic acid; DMSO: Dimethylsulfoxide; elex: Ethanolic leaf extract; erex: Ethanolic root extract; IDF: International Diabetes Federation; MEM: Minimum essential medium; NIDDM: Noninsulin-dependent diabetes mellitus; pNPG: Para-nitrophenyl glucopyranoside; SD: Standard deviation; T2D: Type 2 diabetes.

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Chemical Group Profiling, In Vitro and In Silico Evaluation of Aristolochia ringens on α-Amylase and α-Glucosidase Activity.

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