Capnellene, a natural marine compound derived from soft coral, attenuates chronic constriction injury-induced neuropathic pain in rats
Capnellene, a natural marine compound derived from soft coral, attenuates chronic constriction injury-induced neuropathic pain in rats
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DOI：
10.1111/j.1476-5381.2009.00323.x
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发表时间：
2009-10-01
影响因子：
7.3
通讯作者：
Wen, Zhi-Hong
中科院分区：
文献类型：
--
作者：
Jean, Yen-Hsuan;Chen, Wu-Fu;Wen, Zhi-Hong
背景与目的：从海洋生物中获得的天然化合物作为治疗人类炎症性疾病的潜在药物来源受到了广泛关注。Capnellene是从海洋软珊瑚Capnellaimbricate中分离得到的一种新化合物，4，4，6a-三甲基-3-亚甲基-十氢-环戊二烯并[e]并环戊二烯-2，3a-二醇（GB 9），在体外对活化的巨噬细胞具有抗炎作用。在此，我们评估了GB 9及其乙酰化衍生物，乙酸3 α-羟基-4，4，6 α-三甲基-3-亚甲基-十氢-环戊二烯并[e]并环戊二烯-2-基酯（GB 10）的抗神经炎特性。实验方法：通过Western印迹法测量GB 9或GB 10对干扰素-γ（IFN-γ）刺激的小鼠小胶质细胞BV 2中诱导型一氧化氮合酶（iNOS）和环氧合酶-2（考克斯-2）表达的影响。这些化合物的体内效应在慢性压迫性损伤（CCI）大鼠神经病理性疼痛模型中进行了检查，测量热痛觉过敏，和腰脊髓中的小胶质细胞活化和考克斯-2蛋白，通过免疫组化，关键结果：在BV 2细胞中，GB 9和GB 10抑制了由IFN-γ刺激的iNOS和考克斯-2的表达。鞘内注射GB 9和GB 10以剂量依赖的方式抑制CCI诱导的伤害性敏化和热痛觉过敏。腹腔注射GB 9抑制CCI诱导的热痛觉过敏，也抑制CCI诱导的小胶质细胞的激活和上调考克斯-2的腰脊髓同侧的背角的injuries.Conclusion和影响：两者合计，这些数据表明，海洋来源的capnellenes，GB 9和GB 10，具有抗神经炎症和抗伤害性的特性，在IFN-γ刺激的小胶质细胞和神经病大鼠分别。因此，capnellene可能作为一个有用的先导化合物在寻找新的治疗药物用于治疗神经炎症性疾病。
Background and purpose:Natural compounds obtained from marine organisms have received considerable attention as potential sources of novel drugs for treatment of human inflammatory diseases. Capnellene, isolated from the marine soft coral Capnella imbricate, 4,4,6a-trimethyl-3-methylene-decahydro-cyclopenta[e]pentalene-2,3a-diol (GB9) exhibited anti-inflammatory actions on activated macrophages in vitro. Here we have assessed the anti-neuroinflammatory properties of GB9 and its acetylated derivative, acetic acid 3a-hydroxy-4,4,6a-trimethyl-3-methylene-decahydro-cyclopenta[e]pentalen-2-yl ester (GB10).Experimental approach:Effects of GB9 or GB10 on the expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in interferon-gamma (IFN-gamma)-stimulated mouse microglial BV2 cells were measured by Western blot. The in vivo effects of these compounds were examined in the chronic constriction injury (CCI) rat model of neuropathic pain, measuring thermal hyperalgesia, and microglial activation and COX-2 protein in lumbar spinal cord, by immunohistochemistry.Key results:In BV2 cells, GB9 and GB10 inhibited the expression of iNOS and COX-2, stimulated by IFN-gamma. Intrathecal administration of GB9 and GB10 inhibited CCI-induced nociceptive sensitization and thermal hyperalgesia in a dose-dependent manner. Intraperitoneal injection of GB9 inhibited CCI-induced thermal hyperalgesia and also inhibited CCI-induced activation of microglial cells and up-regulation of COX-2 in the dorsal horn of the lumbar spinal cord ipsilateral to the injury.Conclusion and implications:Taken together, these data indicate that the marine-derived capnellenes, GB9 and GB10, had anti-neuroinflammatory and anti-nociceptive properties in IFN-gamma-stimulated microglial cells and in neuropathic rats respectively. Therefore, capnellene may serve as a useful lead compound in the search for new therapeutic agents for treatment of neuroinflammatory diseases.