Antinociceptive efficacy of verticinone in murine models of inflammatory pain and paclitaxel induced neuropathic pain.
Antinociceptive efficacy of verticinone in murine models of inflammatory pain and paclitaxel induced neuropathic pain.
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DOI：
10.1248/bpb.34.1377
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发表时间：
2011-09
影响因子：
2
通讯作者：
Fang-zhou Xu;Shongzhou Xu;Lijun Wang;Chun-hua Chen;Xueqing Zhou;Yuzhen Lu;Huihui Zhang
中科院分区：
文献类型：
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作者：
Fang-zhou Xu;Shongzhou Xu;Lijun Wang;Chun-hua Chen;Xueqing Zhou;Yuzhen Lu;Huihui Zhang
从贝母(贝母)中分离得到一种异甾体类生物碱，对其镇痛活性进行了小鼠炎症和神经病理性疼痛模型研究。结果表明，灌胃给药能明显抑制醋酸引起的小鼠扭体反应，呈剂量依赖关系，其中3 mg/kg剂量组的扭体抑制率为66.2%，接近200 mg/kg阿司匹林的抑制率。在福尔马林实验中，高剂量(3 mg/kg)的轮枝酮可抑制两个时相的伤害性反应，而小剂量(1.5 mg/kg)仅抑制第二时相的反应，提示轮枝素可能通过中枢和外周机制发挥其镇痛作用。此外，在福尔马林和醋酸实验中，与赋形剂组相比，马齿藜芦酮处理组小鼠的自发活动显著减少。在紫杉醇诱导的大鼠神经病理性疼痛模型上，与相同剂量重复给药后吗啡的镇痛作用减弱相反，马钱子素具有相对恒定的镇痛作用。这些研究表明，马齿黄素可能通过外周和中枢机制对炎症性疼痛和癌性神经病理性疼痛发挥良好的抗伤害性作用，并可能部分参与镇静作用。在不产生耐受性和依赖性的情况下，马钱子酮有望成为一种新型的镇静止痛药，但其确切的作用机制和活性仍需进一步的研究。
Verticinone, an isosteroidal alkaloid separated from Bulbus Fritillaria (Chinese name "Bei-mu"), was evaluated for its analgesic activities in murine models of inflammatory and neuropathic pain. It was shown that oral administarion of verticinone could significantly inhibit acetic acid-induced writhing response in a dose-dependent way, and the writhing inhibition of 3 mg/kg verticinone was 66.2%, which was approximately higher than that of 200 mg/kg aspirin. In the formalin test, a high dose of (3 mg/kg) verticinone could inhibit the nociceptive response of both phases, but the lower dose (1.5 mg/kg) could only inhibit the second phase response, which suggested that verticinone might exert its analgesic effect through both central and peripheral mechanisms. In addition, in formalin and acetic acid tests, the spontaneous locomotive activities of the mice treated with verticinone were transiently greatly decreased when compared with the vehicle group. In the rat model of paclitaxel induced neuropathic pain, in contrast to the declined analgesic effect of morphine after repeated administration with the same dose, a relatively constant analgesic effect of verticinone was observed. These investigations suggested that verticinone could exert a good antinociceptive effect on inflammatory pain and cancer-related neuropathic pain probably through both peripheral and central mechanisms, and it might be partly involved with some sedation effects. Verticinone is expected to become a potentially novel sedative-analgesic agent without producing tolerance and dependence, but further studies are still urgently needed to elucidate the precise mechanisms and activities of it.