ANTI-INFLAMMATORY AND RELATED PHARMACOLOGICAL PROPERTIES OF A FAGARA EXTRACTIVE AND DBA (A BENZOPYRAN BUTYRIC ACID DERIVATIVE)

Abstract

The anti-inflammatory and related properties of a fagara extractive (fagaramide) and DBA (3, 4-dihydro-2,2 dimethy1-2H-1-benzopyran-6-butyric acid) have been studied. DBA is chemically related to xanthoxylol, natural product from fagara. Carrageenan-induced rat hind paw oedema was used as the model of acute inflammation. DBA and fagaramide were anti-inflammatory when administered orally. The compounds were less potent than indomethacin and about twice as potent as acetylsalicylic acid (Aspirin). Like the non-steroidal anti-Inflammatory compounds, the anti-inflammatory activities of DBA and fagnramide were exerted on the later phase of the acute inflammatory response suggesting that prostaglandins were involved in the action of these compounds. Both DBA and fagaramide inhibited output of prostaglandin-like activity by spontaneously contracting isolated segments of the rabbit ileum. They also inhibited prostaglandin synthesis from arachidonic acid by cell-free homogenates prepared from guinea-pig lungs and rabbit brain. The rank order of potency was similar in both guinea-pig lungs and rabbit brain. Also the rank order of potency was similar to that on carrageenan-induced paw oedema in rats. In the sponge exudates technique, DNA, like the non-steroid anti-inflamatory agenta reduced prosteglandin content of inflammatory exudates. In addition, DBA markedly suppressed leucocyte migration. On the other hand, anti-inflammatory doses of fagaramide had no effect on the prostaglandin and leucocyte content of the inflammatory exudates. Neither DBA nor fagaramide reduced amine (histamine and 5-hydroxytrypta-mine) content of the inflammatory exudate. Analgesic activity was tested on acetic acid induced squirming response in mice. Both DBA and fagaramide reduced acetic acid induced squirming response and dye leakage into the viscera dose-dependently. DBA was more potent than fagaramide in this test. In a small number of animals, DBA was weakly antipyretic (tested on pyrogen-induced hyperthermic response in conscious rabbits) while fagaramide was not anti-pyretic at anti-inflammatory and analgesic doses. PharmacodYnamic studies on various isolated pharmaco-logical preparations showed that DBA was inactive on the logical parasympathetic nervous system except for weak muscarinic effects on guinea-pig and rabbit ilea. It has no action on the rat blood pressure. Fagaramide had variable effects on motor nerve-skeletal muscle preparations, depressant effects on smooth muscle and no effect on the rat blood pressure. It was concluded that the anti-inflammatory action-of DBA was mediated through inhibition of prostaglandin synthesis and suppression of leucocyte migration. On the other hand, the anti-inflammatory effect of fagaramide seemed unrelated to prostaglandin synthetase inhibition. Neither did it involve inhibition of leucocyte and amine (histamine and 5-hydroxytryptamine) exudation into the inflammatory exudate. A possible mode of action is discussed.