Wang J P, Raung S L, Chang L C, Kuo S C
Department of Medical Research, Taichung Veterans General Hospital, Taiwan.
Eur J Pharmacol. 1995 Jan 5;272(1):87-95. doi: 10.1016/0014-2999(94)00627-j.
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.
乙酰紫草素是从中药材紫草中分离得到的一种萘醌，已证明它能抑制正常小鼠和去肾上腺小鼠中多粘菌素B诱导的后爪水肿。用乙酰紫草素预处理去肾上腺小鼠，其肝糖原含量并未增加，而用地塞米松预处理的去肾上腺小鼠肝糖原含量增加。与苯海拉明、甲基麦角新碱和异丙肾上腺素一样，乙酰紫草素可减少通过隐神经逆向刺激在背侧后爪皮肤诱发的血浆渗出，以及在被动皮肤过敏反应、缓激肽、P物质、化合物48/80、组胺和5-羟色胺诱导的耳部水肿中出现的血浆渗出。在这些方面，吲哚美辛无效。当分别将[Thi5,8,D-Phe7]缓激肽和[D-Pro2,D-Trp7,9]P物质与缓激肽和P物质共同注射时，缓激肽和P物质诱导的血浆渗出也显著减少。在分离的大鼠腹膜肥大细胞制剂中，乙酰紫草素对化合物48/80刺激的肥大细胞释放组胺和β-葡萄糖醛酸酶产生浓度依赖性抑制作用。在化合物48/80预处理的小鼠中，与苯海拉明联合甲基麦角新碱相比，乙酰紫草素和异丙肾上腺素对缓激肽和P物质诱导的血浆渗出产生的抑制作用明显更强。在化合物48/80预处理的小鼠中，如果分别将[Thi5,8,D-Phe7]缓激肽和[D-Pro2,D-Trp7,9]P物质与缓激肽或P物质共同注射，用苯海拉明/甲基麦角新碱预处理可进一步显著降低缓激肽和P物质诱导的血浆渗出。结果表明，乙酰紫草素对水肿反应的抑制作用既不是由于肾上腺释放类固醇激素，也不是由于糖皮质激素活性，而可能部分是由于抑制肥大细胞脱颗粒，部分是由于保护血管免受介质攻击。
