Acetylshikonin, a naphthoquinone isolated from the Chinese herb medicine, tzu ts'ao,
was demonstrated to inhibit the polymyxin B-induced hind-paw edema in normal as well
as in adrenalectomized mice. Liver glycogen content was increased in adrenalectomized
mice pretreated with dexamethasone, but not with acetylshikonin. Like diphenhydramine,
methysergide and isoproterenol, acetylshikonin reduced the plasma exudation evoked
in dorsal hind-paw skin by antidromic stimulation of the saphenous nerve, and in passive
cutaneous anaphylactic reaction, bradykinin-, substance P-, compound 48/80-, histamine-
and serotonin-induced ear edema. Indomethacin was ineffective in these respects. Bradykinin-
and substance P-induced plasma exudation were also significantly reduced when [Thi5,8,D-Phe7]bradykinin
and [D-Pro2,D-Trp7,9]substance P were coinjected with bradykinin and substance P,
respectively. In isolated 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 significantly more inhibitory effect on bradykinin- and
substance P-induced plasma exudation than did diphenhydramine in combination with
methysergide. Pretreatment with diphenhydramine/methysergide in compound 48/80-pretreated
mice significantly further reduced the bradykinin- and substance P-induced plasma
exudation if [Thi5,8,D-Phe7]bradykinin and [D-Pro2,D-Trp7,9]substance P were coinjected
with bradykinin or substance P, respectively. The results suggest that the inhibitory
effect of acetylshikonin on the edematous response is due neither to the release of
steroid hormones from the adrenal gland nor to the glucocorticoid activity, but probably
partly to the suppression of mast cell degranulation and partly to protection of the
vasculature from mediator challenge.