Ultrapotent effects of salvinorin A, a hallucinogenic compound from Salvia divinorum, on LPS-stimulated murine macrophages and its anti-inflammatory action in vivo
Ultrapotent effects of salvinorin A, a hallucinogenic compound from Salvia divinorum, on LPS-stimulated murine macrophages and its anti-inflammatory action in vivo
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DOI：
10.1007/s00109-011-0752-4
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发表时间：
2011-09-01
影响因子：
4.7
通讯作者：
Capasso, Raffaele
中科院分区：
文献类型：
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作者：
Aviello, Gabriella;Borrelli, Francesca;Capasso, Raffaele
致幻化合物salvinorin A是一种有效的κ阿片受体（KOR）激动剂。然而，其他目标（S）比KOR，如大麻素CB 1受体，已被提出来解释其多种药理作用。在此，我们评估了鼠尾草素A在脂多糖（LPS）刺激的巨噬细胞以及体内炎症模型中的作用。鼠尾草素A（0.1-10 pM）降低LPS刺激的亚硝酸盐、TNF-α和IL-10（但不降低IL-1 β）水平以及iNOS（但不降低考克斯-2）LPS诱导的过度表达。salvinorin A对亚硝酸盐水平的影响被阿片类药物拮抗剂纳洛酮、KOR拮抗剂nor-binaltorphimine和CB 1拮抗剂利莫那班逆转，Salvinorin A也阻止了LPS诱导的KOR和CB 1过表达。在体内，鼠尾草素A以去甲binaltorphimine和利莫那班敏感的方式减少LPS和角叉菜胶诱导的爪水肿和福尔马林诱导的炎性疼痛。可以得出结论，鼠尾草素A-通过KORs和CB 1受体-发挥对巨噬细胞的超强效作用，并在体内也显示出中度抗炎作用。
The hallucinogenic compound, salvinorin A, is a potent kappa-opioid receptor (KOR) agonist. However, other target(s) than the KOR, such as the cannabinoid CB1 receptor, have been proposed to explain its multiple pharmacological actions. Here, we have evaluated the effect of salvinorin A in lipopolysaccharide (LPS)-stimulated macrophages as well as in models of inflammation in vivo. Salvinorin A (0.1-10 pM) reduced LPS-stimulated nitrite, TNF-alpha and IL-10 (but not IL-1 beta) levels as well as iNOS (but not COX-2) LPS-induced hyperexpression. The effect of salvinorin A on nitrite levels was reverted by the opioid antagonist naloxone, the KOR antagonist nor-binaltorphimine and by the CB1 antagonist rimonabant Salvinorin A also prevented KOR and CB1 hyperexpression induced by LPS. In vivo, salvinorin A reduced the LPS- and the carrageenan-induced paw oedema and formalin-induced inflammatory pain, in a nor-binaltorphimine and rimonabant-sensitive manner. It is concluded that salvinorin A-via KORs and CB1 receptors-exerts ultrapotent actions on macrophages and also shows moderate antinflammatory effects in vivo.