Andoh Tsugunobu, Uta Daisuke, Kato Mitsuru, Toume Kazufumi, Komatsu Katsuko, Kuraishi Yasushi
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama.
Biol Pharm Bull. 2017;40(4):473-478. doi: 10.1248/bpb.b16-00899.
Paclitaxel is a chemotherapeutic agent that causes peripheral neuropathy as its major dose-limiting side effect. However, the peripheral neuropathy is difficult to manage. A study we recently conducted showed that repetitive administration of aucubin as a prophylactic inhibits paclitaxel-induced mechanical allodynia. However, the mechanisms underlying the anti-allodynic activity of aucubin, which is a major component of Plantaginis Semen, was unclear. In addition to mechanical allodynia, aucubin inhibited spontaneous and mechanical stimuli-induced firing in spinal dorsal horn neurons; however, catalpol, a metabolite of aucubin, did not show these effects. Furthermore, paclitaxel induced the expression of CCAAT/enhancer-binding protein homologous protein, a marker of endoplasmic reticulum (ER) stress, in the sciatic nerve and a Schwann cell line (LY-PPB6 cells); however, this effect was inhibited by aucubin. These results suggest that aucubin inhibits paclitaxel-induced mechanical allodynia through the inhibition of ER stress in peripheral Schwann cells.
紫杉醇是一种化疗药物，其主要剂量限制性副作用是引起周围神经病变。然而，这种周围神经病变难以处理。我们最近进行的一项研究表明，重复给予桃叶珊瑚苷作为预防措施可抑制紫杉醇诱导的机械性异常性疼痛。然而，桃叶珊瑚苷作为车前子的主要成分，其抗异常性疼痛活性的潜在机制尚不清楚。除了机械性异常性疼痛外，桃叶珊瑚苷还抑制脊髓背角神经元的自发和机械刺激诱发的放电；然而，桃叶珊瑚苷的代谢产物梓醇并未表现出这些作用。此外，紫杉醇可诱导坐骨神经和雪旺细胞系（LY-PPB6细胞）中内质网（ER）应激标志物CCAAT/增强子结合蛋白同源蛋白的表达；然而，这种作用被桃叶珊瑚苷抑制。这些结果表明，桃叶珊瑚苷通过抑制外周雪旺细胞中的ER应激来抑制紫杉醇诱导的机械性异常性疼痛。
