Background: Different parts of A. conyzoides have been widely used in traditional medicine for therapeutic purposes, and it contains enormous secondary metabolites such as phenolics with varied biological activities. Poor druggability has caused many candidate compounds showing excellent in-vitro efficacy to be dismissed, which can be minimized in early drug discovery by in-silico drug-like prediction and virtual screening. Thus, this study was aimed at evaluating the antidiabetic potentials of phenolic compounds (furocoumarinic acid, liquiritin, isorhamnetin and syringin) identified from ethyl acetate fraction of A. conyzoides methanol leaf extract.
Methods: SwissADME and ADMETlab 2.0 software tools were used to predict the drug-likeness of the compounds, and AutoDock Vina and UCSF Chimera were used for docking studies. The compound that showed best interaction with receptors (target proteins) was then experimentally validated through fasting blood glucose (FBG) assay.
Results: Findings of this study indicated that all the four phenolics were found to have good drug-like potential according to the rule-based filter models, with oral bioavailability scores of 55% better than acarbose (17%). However, of the four phenolics, only isorhamnetin was able to demonstrate good interactions with target receptors, indicating an outstanding inhibitory effect on aldose reductase (AR), dipeptidyl peptidase 4, and glutamine fructose-6-phosphate amidotransferase (GFAT). Experimental validation indicated that FBG levels of the diabetic control (untreated) group, acarbose- and isorhamnetin-treated groups were 421.00±9.10, 232.40±6.15, and 239.60±8.56 mg/dL, respectively, with a corresponding percentage decrease of 10.65±3.20, 52.07±1.78, and 50.13±2.60 respectively.
Conclusion: This study has demonstrated that furocoumarinic acid, liquiritin, isorhamnetin, and syringin from ethyl acetate fraction of A. conyzoides methanol leaf exhibited good drug-likeness potentials with 55% oral bioavailability. Out of which, only isorhamnetin was able to inhibit AR, DPP-4, and GFAT activities, and activate glucokinase through docking studies.
Ageratum conyzoides, phenolics, druggability, molecular docking, isorhamnetin, and diabetes mellitus
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