Absorption, distribution, metabolism, excretion, and toxicity evaluation of Papua red fruit flavonoids through a computational study

Abstract

Red Fruit (RF) (Pandanus conoideus Lam.) was used as traditional medicine for Papuans and consumed as a daily meal. RF was proved as a source of bioactive antioxidant and anticancer, grace on their flavonoids. There was a few researches that focuses on the metabolism and toxicity of RF, but the mechanism of metabolism and toxicity of the flavonoids present in the RF is unclear. This research aims to evaluate the absorption, distribution, metabolism, excretion, and toxicity of RF flavonoids through computational study, sharpening their potency as bioactive in functional food. Flavonoids in RF extracts were identified using LCMS and or obtained from secondary data. The chemical structure of the flavonoids was redrawn to get the canonical of the molecular graph. Absorption, distribution, metabolism, and excretion were predicted using SWISS ADME, OSIRIS Property Explorer, and hERG-Pred. Those were based on the physicochemical properties, pharmacokinetic, BOILED-EGG test, whereas the toxicology based on the potency as a toxicant, P-gp substrate, hERG blocker, and CYP450 inhibitor. Quercetin, Taxifolin, and Quercetin 3-Glucoside were identified in the methanol and ethyl acetate extract. Quercetin, Taxifolin, 3,4,5-trihydroxy-7,3-dimethoxyflavone/TDF, 4',6,6',8-tetrahidroksi-3-metoksi-flavon/TMF, and Quercetin3-Methyl-Ether/QME fulfilled the RO5 parameters; they were higher in water solubility, gastrointestinal absorption, and bioavailability. All were not P-gp substrate and hERG blocker, but some of them were CYP450 inhibitors. Only TMF, QME, Taxifolin3-O-α-Arabinopiranose/TAP, and Quercetin3-O-Glucose/QOG that consistently had no risk as toxic compounds. RF flavonoid showed high potency as bioactive. Most of the flavonoid had no toxicity risk. Generally, RF flavonoids were categorised as safe.