Zinagrandinolide E (1, ZGE) is an elemanolide with antinociceptive action isolated from Zinnia grandiflora (Asteraceae), valued in North México and southwestern United States for pain relief. Herein, we report the anti-inflammatory and antiallodynic action of ZGE (1) in carrageenan-induced inflammation and tactile allodynia in mice and in a neuropathic pain model in hyperglycemic mice. Local peripheral administration of ZGE (1–30 μg/paw) induced dose-dependent acute anti-inflammatory and antiallodynic effects. The anti-inflammatory effect was comparable to diclofenac (30 μg/paw). Intrathecal (i.t.) administration of ZGE (30 μg) in acute experiments did not affect carrageenan-induced inflammation but significantly reduced tactile allodynia in a dose-dependent fashion. In long-term experiments (15 or 6 days), using two different scheme treatments (pretreatment or post-treatment), ZGE (3–30 μg/paw) showed antiallodynic but not anti-inflammatory action. Local peripheral (3–30 μg/paw) or intrathecal (3–30 μg) administration of ZGE partially reversed tactile allodynia in hyperglycemic mice, better or comparable, respectively, with those of pregabalin (30 μg/paw or 30 μg i.t.). The effects were dose-dependent. According to the pharmacological tools employed, the anti-inflammatory and antiallodynic activities of ZGE are multitarget; these involve the opioidergic, serotoninergic, and GABAergic systems, as well as the NO-cGMP-ATP-sensitive K⁺ channel signaling pathway.

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大花百日草Zinagrandinolide E对小鼠抗炎及镇痛作用的药理分析

Zinagrandinolide E ( 1 , ZGE) 是一种从大花百日草（菊科）中分离出来的具有镇痛作用的榄香脂内酯，在墨西哥北部和美国西南部具有镇痛作用。在此，我们报告了 ZGE 的抗炎和抗异常性疼痛作用（1) 在小鼠角叉菜胶诱导的炎症和触觉异常性疼痛中以及在高血糖小鼠的神经性疼痛模型中。ZGE（1-30 μg/爪）的局部外周给药诱导剂量依赖性的急性抗炎和抗异常性疼痛作用。抗炎作用与双氯芬酸（30 μg/爪）相当。在急性实验中鞘内 (it) 施用 ZGE (30 μg) 不影响角叉菜胶诱导的炎症，但以剂量依赖性方式显着减少触觉异常性疼痛。在长期实验（15 或 6 天）中，使用两种不同的方案处理（预处理或后处理），ZGE（3-30 μg/爪）显示出抗异常性疼痛但不具有抗炎作用。局部外周 (3-30 μg/爪) 或鞘内 (3-30 μg) 给药 ZGE 部分逆转了高血糖小鼠的触觉异常性疼痛，更好或相当，分别与普瑞巴林（30 μg/爪或 30 μg it）的那些。效果是剂量依赖性的。根据所采用的药理手段，ZGE 的抗炎和镇痛作用是多靶点的；这些涉及阿片能、血清素能和 GABA 能系统，以及 NO-c GMP-ATP 敏感的 K ⁺通道信号通路。