Studies on the mechanism of anti-inflammatory activities of papyriogenin a and papyriogenin C.

The mechanism of anti-inflammatory action of papyriogenin A and C, obtained from Tetrapanax papyriferum, were investigated by the following methods; the cotton pellet granuloma test in normal and adrenalectomized rats, the blockade by anti-glucocorticoids of vascular permeability caused by serotonin in mice and the competition on 5 beta-reduction of steroidal compounds. The anti-inflammatory activity was observed in the decreasing order; papyriogenin C greater than papyriogenin A on the carrageenin-induced paw edema in mice, as reported in our previous paper. In a serotonin-induced paw edema, pretreatment with progesterone (50, 100 and 200 mg/kg) blocked completely the anti-inflammatory effects of papyriogenin A or C at 10 and 50 mg/kg. When actinomycin D (1 and 2 mg/kg) or cycloheximide (6 mg/kg) was given twice, simultaneously with papyriogenin A or C, during the latent period for the manifestation of the anti-inflammatory effect, the anti-inflammatory effects of papyriogenin A and C were blocked completely by s.c. administration. The effects of papyriogenin A or C, 30 mg/kg p.o., on the cotton pellet granuloma test in adrenalectomized rats were similar to those of normal rats. On the other hand, the competitive effects of papyriogenin A and C on 5 beta-reduction of testosterone and cortisol were recognized to be significant. These activities of papyriogenin A and C are explained by their steroidal actions in the target cell and their competitive effects in endogenous corticoid metabolism in liver.