Processed aconite root and its active ingredient neoline may alleviate oxaliplatin-induced peripheral neuropathic pain
Processed aconite root and its active ingredient neoline may alleviate oxaliplatin-induced peripheral neuropathic pain
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DOI：
10.1016/j.jep.2016.03.056
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发表时间：
2016-06-20
影响因子：
5.4
通讯作者：
Makino, Toshiaki
中科院分区：
文献类型：
--
作者：
Suzuki, Toshiaki;Miyamoto, Keisuke;Makino, Toshiaki
民族药理学相关性：加工附子根（PA，毛茛科乌头的根）是传统中国或日本汉方药物中使用的生药，可在体内产生热量并治疗与寒冷相关的疼痛。奥沙利铂（L-OHP）是一种铂类抗癌药物，经常引起急性和慢性周围神经病变，包括冷痛和机械性痛觉过敏。研究目的：我们研究了PA对L-OHP引起的周围神经病变的影响，并鉴定了PA提取物中的活性成分。材料和方法：将L-OHP腹腔注射到小鼠体内，并口服PA煮水提取物。分别使用丙酮试验和冯弗雷丝法评估冷痛和机械痛觉过敏。从正常小鼠中分离出背根神经节 (DRG) 神经元，并用含有或不含 PA 提取物的 L-OHP 进行培养。评估细胞活力和神经突伸长。结果：PA 提取物显着减弱 L-OHP 引起的小鼠寒冷和机械痛觉过敏。在培养的 DRG 神经元中，L-OHP 以剂量依赖性方式降低细胞活力和神经突伸长。 PA提取物处理显着缓解了L-OHP引起的神经突伸长减少，而L-OHP的细胞毒性不受影响。通过活性引导分馏，我们从 PA 提取物中分离出新林作为活性成分。 Neoline 以浓度依赖性方式显着减轻 L-OHP 诱导的培养 DRG 神经元中神经突伸长的减少。此外，皮下注射新林可减轻 L-OHP 治疗小鼠的冷痛和机械痛觉过敏。 PA提取物和neoline没有表现出镇静和运动障碍。结论：本研究表明PA及其活性成分neoline是缓解L-OHP引起的神经性疼痛的有前途的药物。 (C) 2016 Elsevier Ireland Ltd. 保留所有权利。
Ethnopharmacological relevance: Processed aconite root (PA, the root of Aconitum carmichaeli, Ranunculaceae) is a crude drug used in traditional Chinese or Japanese kampo medicine to generate heat in the body and to treat pain associated with coldness. Oxaliplatin (L-OHP) is a platinum-based anticancer drug that frequently causes acute and chronic peripheral neuropathies, including cold and mechanical hyperalgesia.Aim of the study: We investigated the effects of PA on L-OHP-induced peripheral neuropathies and identified the active ingredient within PA extract.Materials and methods: L-OHP was intraperitoneally injected into mice, and PA boiled water extract was orally administered. Cold and mechanical hyperalgesia were evaluated using the acetone test and the von Frey filament method, respectively. Dorsal root ganglion (DRG) neurons were isolated from normal mice and cultured with L-OHP with or without PA extract. Cell viability and neurite elongation were evaluated.Results: PA extract significantly attenuated cold and mechanical hyperalgesia induced by L-OHP in mice. In cultured DRG neurons, L-OHP reduced cell viability and neurite elongation in a dose-dependent manner. Treatment with PA extract significantly alleviated the L-OHP-induced reduction of neurite elongation, while the cytotoxicity of L-OHP was not affected. Using activity-guided fractionation, we isolated neoline from PA extract as the active ingredient. Neoline significantly alleviated L-OHP-induced reduction of neurite elongation in cultured DRG neurons in a concentration-dependent manner. Moreover, subcutaneous injection of neoline attenuated cold and mechanical hyperalgesia in L-OHP-treated mice. PA extract and neoline did not show sedation and motor impairment.Conclusions: The present study indicates that PA and its active ingredient neoline are promising agents to alleviate L-OHP-induced neuropathic pain. (C) 2016 Elsevier Ireland Ltd. All rights reserved.