Neoline is the active ingredient of processed aconite root against murine peripheral neuropathic pain model, and its pharmacokinetics in rats
Neoline is the active ingredient of processed aconite root against murine peripheral neuropathic pain model, and its pharmacokinetics in rats
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DOI：
10.1016/j.jep.2019.111859
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发表时间：
2019-09-15
影响因子：
5.4
通讯作者：
Makino, Toshiaki
中科院分区：
文献类型：
--
作者：
Tanimura, Yohei;Yoshida, Masato;Makino, Toshiaki
民族药理学相关性：附子是毛茛科植物附子的根，是中国传统医药或日本汉方医药中用于治疗与寒冷有关的疼痛的原料药。在我们以前的研究中，PA及其活性成分neoline减轻了奥沙利铂诱导的小鼠周围神经病变。本研究的目的：本研究探讨PA对腹腔注射紫杉醇和部分结扎坐骨神经诱导的小鼠周围神经病变模型的影响（Seltzer模型），并鉴定了其活性成分。PA粉末（1 g/kg/天）经口给药，并将纽林或苯甲酰基新乌头碱（10 mg/kg/天）皮下注射到小鼠模型中。通过von Frey细丝法评价机械性痛觉过敏。PA提取物经口给药大鼠，按时间顺序收集血液样品，并测定血浆中生物碱的浓度。结果：PA提取物和新碱对紫杉醇所致的小鼠机械性痛敏和坐骨神经部分结扎所致的小鼠机械性痛敏均有明显的抑制作用。在用PA提取物处理的大鼠的血浆样品中，苯甲酰基新乌头碱和新碱的浓度明显高于乌头生物碱。不同加工工艺的PA产品中苯甲酰新乌头碱和新乌头碱的含量不同。皮下注射苯甲酰基新乌头碱没有减弱由每个紫杉醇，坐骨神经部分结扎，或奥沙利铂在mice.Conclusions：目前的研究结果表明，PA及其活性成分，neoline，是有前途的代理人，用于缓解神经病理性疼痛。Neoline可用作标记化合物以确定用于治疗神经性疼痛的PA产品的质量。
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 treat pain associated with coldness. In our previous study, PA and its active ingredient, neoline, alleviated oxaliplatin-induced peripheral neuropathy in mice.Aim of the study: The present study investigated the effects of PA on a murine peripheral neuropathy model induced by intraperitoneal injection of paclitaxel and partial ligation of the sciatic nerve (Seltzer model), and identified its active ingredients.Materials and methods: PA powder (1 g/kg/day) was orally administered, and either neoline or benzoylmesaconine (10 mg/kg/day) was subcutaneously injected into the murine model. Mechanical hyperalgesia was evaluated via the von Frey filament method. PA extract was orally administered to rats; blood samples were chronologically collected, and the plasma concentrations of Aconitum alkaloids were measured. The contents of Aconitum alkaloids in commercial PA products were also measured.Results: PA extract and neoline significantly attenuated the mechanical hyperalgesia induced by either paclitaxel or partial ligation of the sciatic nerve in mice. In the plasma samples of rats treated with PA extract, higher concentrations of benzoylmesaconine and neoline were apparent among Aconitum alkaloids. The contents of benzoylmesaconine and neoline varied among PA products with different processing procedures. Subcutaneous injection of benzoylmesaconine did not attenuate the hyperalgesia induced by each paclitaxel, partial ligation of the sciatic nerve, or oxaliplatin in mice.Conclusions: The present results indicate that PA and its active ingredient, neoline, are promising agents for the alleviation of neuropathic pain. Neoline can be used as a marker compound to determine the quality of the PA products for the treatment of neuropathic pain.