In vitro inhibitory effects of flavonoids from the extracts of Artocarpus species on prostaglandin E2(PGE2) production in human plasma

Abstract

In this study, seven flavonoids from several Artocarpus species, artocarpin (1),  isobavachalcone (2), cycloheterophyllin (3), 2',4'-dihydroxy-4-methoxy-3'-prenyldihydrochalcone (4), 4',5-dihydroxy-6,7-(2,2-dimethylpyrano)-2'-methoxy-8-γ,γ –dimethylallylflavone (5), artonin E (6) and oxyresveratrol (7) were investigated for their inhibitory effects on the production of prostaglandin E₂ (PGE₂) in human plasma.The inhibitory effect of seven compounds isolated from several Artocarpus species was determined by measuring the PGE₂ level in plasma using radioimmunoassay (RIA) technique. Radiolabelled antigen, [³H]-PGE₂ that bound with antibody was displaced by unlabelled antigen present in plasma. The unbound radiolabelled antigen was calculated using liquid scintillation counter. Among the seven flavonoids, artocarpin (1) showed the highest inhibition of 68.1%, followed by artonin E (6) and isobavachalcone (2) with 66.8% and 63.9% inhibition respectively. Meanwhile, cycloheterophyllin (3) exhibited the lowest inhibition with 21.5%. Compound 1, 4, 5 and 6 were the most potent inhibitor in inhibit the biosynthesis of PGE₂ with IC₅₀ value of 11.66 µM, 8.99 µM, 7.04 µM and 8.98 µM, respectively. These results showed that compound 1,4, 5 and 6 inhibited the activity of PGE₂ production in human blood induces by lipopolysaccharide (LPS), indicating that it might directly inhibit cyclooxygenase-2 (COX-2) enzymatic activity. Different substitution pattern of the flavonoids may contribute in different range of inhibitory activity