Actions of flavonoids and the novel anti-inflammatory flavone, hypolaetin-8-glucoside, on prostaglandin biosynthesis and inactivation.

The newly identified plant-derived flavone-glycoside hypolaetin-8-glucoside, which has anti-inflammatory and gastric ulcer protective properties, and its corresponding aglycone, hypolaetin, were tested for effects on prostaglandin biosynthesis and degradation. They were compared with four other flavonoids, viz. rutin and its corresponding aglycone, quercetin, and the aglycones isoscutellarein and kaempferol. Over the range 10-1000 microM the glycosides rutin and hypolaetin-8-glucoside stimulated prostaglandin formation by sheep seminal vesicle microsomes incubated with radiolabelled arachidonic acid; the other compounds were essentially inactive. Over 5-5000 microM rutin and hypolaetin-8-glucoside enhanced the release of prostacyclin (and other prostanoids) from fragments of rat caecum incubated in the absence of additional arachidonic acid; the four aglycones compounds did not stimulate prostacyclin release but some reduced it at 5000 microM. However, the glycosides did not affect the enzymatic inactivation of radiolabelled prostaglandin F2 alpha by semi-purified bovine lung prostaglandin 15-hydroxydehydrogenase (PGDH) or in 100,000 g supernatants prepared from homogenised rat stomach. Three of the four aglycones (quercetin, kaempferol, isoscutellarein, in descending order of potency) were inhibitory to PGDH with ID50 values in the range 130-2100 microM. The results show that the capacity of flavonoids to enhance prostaglandin formation is associated with the presence of glycosidic substitution, whereas PGDH inhibition requires its absence. The relevance of this biochemical profile of hypolaetin-8-glucoside to its anti-inflammatory gastroprotective effects in vivo is discussed.