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.
D000818:Animals; D000893:Anti-Inflammatory Agents; D002199:Capillary Permeability / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D006099:Granuloma / Q000517:prevention & control; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012502:Sapogenins / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D012333:RNA, Messenger; D012502:Sapogenins; D003609:Dactinomycin; D012701:Serotonin; D011374:Progesterone; C038914:papyriogenin A; D009828:Oleanolic Acid; C038913:papyriogenin C; D003513:Cycloheximide