Aldose reductase inhibition by the phenolic bioactive methylripariochromene A from Eupatorium spp

The lens cells of humans with chronic hyperglycemia show a progressive accumulation of sorbitol by aldose reductase catalysis that ends with cell lysis. Therefore, this work aims to explore metabolites in native plants that prevent cataracts through inhibition of the enzyme aldose reductase. The scrutiny was performed using bioinformatics, chemicals, enzymes, and cataract ex vivo prevention techniques. Eleven Eupatorium spp. were the natural resources explored. Five of them were selected to continue with the phytochemical scrutiny. Twelve pure phytometabolites were obtained with an inhibitory effect on the enzyme. Nine of them were subject to the accepted heuristic rules for drug-likeness. With this analysis, a possible active principle emerged a phenolic compound: methylripariochromene A. An apparent mixed catalytic mechanism carries out the inhibition of enzyme catalysis. Molecular docking and molecular dynamic simulations helped us understand their coupling in the active site of AR, finding an agreement between experimental and computational data. Methylripariochromene A prevented experimental cataract formation in rabbit lens cultured ex vivo.