Potential of Active Compounds from Terap (Artocarpus odoratissimus Blanco) Leaves as Antigout through Inhibition of Xanthine Oxidase Enzyme
Terap (Artocarpus odoratissimus Blanco) has the potential to be developed into a drug for treating gout due to its inhibitory activity against the xanthine oxidase enzyme. This study aimed to identify the active compounds in terap leaves that inhibit xanthine oxidase enzymes. A series of studies were conducted: active compounds were separated (through extraction and fractionation with various solvents, as well as isolation); active compound structures were characterized and identified using spectrophotometers (UV, IR, NMR, and MS); and xanthine oxidase enzyme inhibition was tested in vitro and in silico. Additionally, the pharmacokinetic and toxicity profiles of the isolate were predicted. The results showed that the 70 % ethanol extract of terap leaves exhibited xanthine oxidase enzyme inhibitory activity with an IC50 of 89.63 µg/mL. The ethyl acetate fraction was the most active fraction as an inhibitor of xanthine oxidase enzyme from terap leaves with an IC50 of 86.74 µg/mL. The ethyl acetate fraction underwent three stages of isolation using gravity column chromatography and radial chromatography. Isolating the ethyl acetate fraction of terap leaves produced 2 isolates: apigenin and scopoletin. Apigenin was proven to have strong in vitro activity in inhibiting the enzyme xanthine oxidase with an IC50 of 13.45 µM. This activity is nearly equivalent to that of the positive control allopurinol (IC50 10.24 µM). Apigenin and scopoletin interact more strongly and stably with the xanthine oxidase enzyme than hypoxanthine and allopurinol do. Their free energy bond values were -7.4 kcal/mol for apigenin and -7.0 kcal/mol for scopoletin. Apigenin was the most active compound and demonstrated the strongest interaction with the xanthine oxidase enzyme in silico.
The pharmacokinetic profile of apigenin, which is isolated from Terap (A. odoratissimus Blanco) leaves in silico shows that apigenin is well absorbed in the gastrointestinal tract and cannot penetrate the blood-brain barrier. It is moderately distributed in the body (VdSS 0.37) and can inhibit several cytochrome enzymes (CYP1A2, CYP3A4, and CYP2D6) that affect metabolic processes. Apigenin has a short half-life of 0.86 hours and a clearance value smaller than that of allopurinol (7.02 mL/min/kg). Predictions of apigenin toxicity show that this compound is relatively safe from mutagenesis and carcinogenesis and is classified as non-toxic. Apigenin (isolate 01) from terap (A. odoratissimus Blanco) leaves has a good in silico pharmacokinetic profile and is safe.
Key words : Artocarpus odoratissimus, Terap Plants, Xanthine Oxidase, Radial Chromatography, In Vitro Test, In Silico Test, Pharmacokinetics Profile.
