<i>In Silico</i> Prediction of Physiological Activities of Extract of <i>Hibiscus sabdariffa</i> (Hibiscus) Calyces

Hibiscus sabdariffa (commonly known as Roselle) extract is well recognized for its potent antioxidant and enzyme-inhibitory properties, making it a promising candidate for the prevention of oxidative stress-related diseases.In this study, we analyzed the bioactive compounds present in the extract of H. sabdariffa calyces and assessed their inhibitory effects on key enzymes, including angiotensin-converting enzyme (ACE), xanthine oxidase (XO), nicotinamide adenine dinucleotide phosphate oxidase (NOX).Using microwave and ultrasound-assisted extraction with ethanol, more than 13 bioactive compounds were identified via liquid chromatography-tandem mass spectrometry, including anthocyanins, flavanols, and phenolic acids.In silico analysis indicated strong inhibitory potential of myricetin against XO (probability of active [Pa] = 0.866) and gossypin against NOX (Pa = 0.951).Molecular docking further revealed that luteolin and (+)-catechin are potent ACE inhibitors, while myricetin and gossypin effectively target XO and NOX.Myricetin, luteolin, and quercetin showed strong cytochrome P450 3A4 inhibitory activity.A quantitative structure-activity relationship-based multiple linear regression model (R 2 train = 0.670, Q 2LOO = 0.561, R 2 test = 0.675, RMSE train = 0.588, R 2 ext = 0.582) was developed to predict ACE inhibition using the -log 10 (IC 50 ), based on molecular descriptors such as number of heteroatoms, fraction of atoms with formal charge and lipophilicity, although the model exhibited limited predictive accuracy.Bioavailability screening identified luteolin, quercetin, and (+)-catechin as favorable candidates.These findings underscore the potential of H. sabdariffa as a functional food ingredient for managing oxidative stress-related disorders and highlight its usefulness as a preliminary screening tool.