Tornhamre S, Schmidt T J, Näsman-Glaser B, Ericsson I
Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, S-171 77, Stockholm, Sweden.
Biochem Pharmacol. 2001 Oct 1;62(7):903-11. doi: 10.1016/s0006-2952(01)00729-8.
The sesquiterpene lactone helenalin, which can be isolated from several plant species of the Asteraceae family, is a potent anti-inflammatory and antineoplastic agent. In agreement, alcohol extracts of these plants are used for local external treatment of inflammatory conditions. Since leukotrienes are important mediators in inflammatory processes, the inhibitory effects of helenalin and some derivatives on leukotriene (LT) biosynthesis were studied. Treatment of human platelets with helenalin provoked irreversible inhibition of LTC(4) synthase in a concentration- and time-dependent manner with an IC(50) of 12 microM after a 60 min preincubation. 11alpha,13-Dihydrohelenalin acetate was less potent. Interestingly, individual donors could be divided into two distinct groups with respect to the efficacy of helenalin to suppress platelet LTC(4) synthase. In human granulocytes, helenalin inhibited both the 5-lipoxygenase (IC(50) 9 microM after 60 min preincubation) and LTC(4) synthase in a concentration- and time-dependent fashion. In contrast, the drug was without effect on LTA(4) hydrolase. The GSH-containing adducts (2beta-(S-glutathionyl)-2,3-dihydrohelenalin and 2beta-(S-glutathionyl)-2,3,11alpha,13-tetra hydrohelenalin acetate) did not significantly inhibit LTC(4) synthase. The present results indicate a mechanism for the anti-inflammatory effect of helenalin and related compounds.
倍半萜内酯海伦内酯可从菊科的几种植物中分离得到，是一种强效的抗炎和抗肿瘤药物。与此一致的是，这些植物的酒精提取物被用于炎症病症的局部外部治疗。由于白三烯是炎症过程中的重要介质，因此研究了海伦内酯及其一些衍生物对白三烯（LT）生物合成的抑制作用。用海伦内酯处理人血小板会以浓度和时间依赖性方式引起LTC4合酶的不可逆抑制，预孵育60分钟后IC50为12μM。11α，13 - 二氢海伦内酯乙酸酯的效力较低。有趣的是，就海伦内酯抑制血小板LTC4合酶的功效而言，个体供体可分为两个不同的组。在人粒细胞中，海伦内酯以浓度和时间依赖性方式抑制5-脂氧合酶（预孵育60分钟后IC50为9μM）和LTC4合酶。相比之下，该药物对LTA4水解酶没有作用。含谷胱甘肽的加合物（2β-（S-谷胱甘肽基）-2,3-二氢海伦内酯和2β-（S-谷胱甘肽基）-2,3,11α，13-四氢海伦内酯乙酸酯）没有显著抑制LTC4合酶。目前的结果表明了海伦内酯及相关化合物抗炎作用的机制。
