ADME TOXICITY EVALUATION OF PAPUA RED FRUIT FLAVONOIDS THROUGH COMPUTATIONAL STUDY
MARIA MATOETINA SUPRIJONO(a, b), SIMON BAMBANG WIDJANARKO (c) , HIDAYAT SUJUTI (d), DIKDIK KURNIA (e)

a) Department of Food Technology, Agricultural Technology Faculty, Widya Mandala Catholic University Surabaya, Indonesia. Email: maria-matoetina[at]ukwms.ac.id, m.matoetina[at]gmail.com
b) Doctoral Program of Agricultural Product Technology, Agricultural Faculty, Brawijaya University, Malang, Indonesia,
c) Department of Food Science and Technology, Agricultural Technology Faculty, Brawijaya University, Malang, Indonesia,
d) Faculty of Medicine, Brawijaya University, Malang, Indonesia,
e) Department of Chemistry, Faculty of Mathematics and Natural Science, Padjajaran University, Bandung, Indonesia.

Abstract

Introduction: 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; but there is no research focus on the absorption, distribution, metabolism, excretion, and toxicity of RF flavonoids and bioactive. This research wants to evaluate the ADMET of RF flavonoids through computational study, sharpening their potency as bioactive in functional food. Methods: Flavonoids in RF extracts were identified using LCMS. The chemical structure of the flavonoids and five others were redrawn to get the SMILE. ADMET was predicted using SWISS ADME, OSIRIS Property Explorer, and hERG-Pred. The ADME was evaluated 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. Results: Quercetin/Q, Taxifolin/T, and Quercetin 3-Glucoside/Q3G were identified in the methanol and ethyl acetate extract. Q, T, 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 inhibitor. Only TMF, QME, Taxifolin3-O-α-Arabinopiranose/TAP, and Quercetin3-O-Glucose/QOG that consistently had no risk as toxic compounds. Conclusion: ADMET analysis must be done along with bioactive analysis. Some of RF flavonoid showed high potency as bioactive, but with toxicity risk. The structure like TMF and QME were bioactive with low risk of toxicity.

Keywords: ADME, Toxicity, Pandanus conoideus Lam., Red Fruit Flavonoids

Topic: HEALTH, NUTRITION AND MEDICAL MICROBIOLOGY

Link: https://ifory.id/abstract-plain/QYgXNmBHJTbP

Web Format | Corresponding Author (Maria Matoetina Suprijono)