INHIBITION OF HIND-PAW EDEMA AND CUTANEOUS VASCULAR PLASMA EXTRAVASATION IN MICE BY ACETYLSHIKONIN

Acetylshikonin, a naphthoquinone isolated from the Chinese herb medici ne, tzu ts'ao, was demonstrated to inhibit the polymyxin B-induced hin d-paw edema in normal as well as in adrenalectomized mice. Liver glyco gen content was increased in adrenalectomized mice pretreated with dex amethasone, but not with acetylshikonin. Like diphenhydramine, methyse rgide and isoproterenol, acetylshikonin reduced the plasma exudation e voked in dorsal hind-paw skin by antidromic stimulation of the sapheno us nerve, and in passive cutaneous anaphylactic reaction, bradykinin-, substance P-, compound 48/80-, histamine- and serotonin-induced ear e dema. Indomethacin was ineffective in these respects. Bradykinin- and substance P-induced plasma exudation were also significantly reduced w hen [Thi(5,8),D-phe(7)]bradykinin and [D-Pro(2),D-Trp(7,9)]substance P were coinjected with bradykinin and substance P, respectively. In iso lated rat peritoneal mast cell preparation, acetylshikonin produced a concentration-dependent inhibition of histamine and beta-glucuronidase release from mast cells challenged by compound 48/80. In compound 48/ 80-pretreated mice, acetylshikonin and isoproterenol produced signific antly more inhibitory effect on bradykinin- and substance P-induced pl asma exudation than did diphenhydramine in combination with methysergi de. Pretreatment with diphenhydramine/methysergide in compound 48/80-p retreated mice significantly further reduced the bradykinin- and subst ance P-induced plasma exudation if [Thi(5,8),D-Phe(7)]bradykinin and [ D-Pro(2),D-Trp(7,9)]substance P were coinjected with bradykinin or sub stance P, respectively. The results suggest that the inhibitory effect of acetylshikonin on the edematous response is due neither to the rel ease of steroid hormones from the adrenal gland nor to the glucocortic oid activity, but probably partly to the suppression of mast cell degr anulation and partly to protection of the vasculature from mediator ch allenge.