title: Prophylactic Administration of Aucubin Inhibits Paclitaxel-Induced Mechanical Allodynia via the Inhibition of Endoplasmic Reticulum Stress in Peripheral Schwann Cells.
abstract: 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.
authors.affiliation: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama.
authors.forename: Tsugunobu
authors.initials: T
authors.lastname: Andoh
authors.forename: Daisuke
authors.initials: D
authors.lastname: Uta
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kato
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Toume
authors.forename: Katsuko
authors.initials: K
authors.lastname: Komatsu
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kuraishi
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000502:physiology; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D057888:Iridoid Glucosides / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000037:antagonists & inhibitors / Q000633:toxicity*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D065129:Pre-Exposure Prophylaxis / Q000379:methods*; D051381:Rats; D012583:Schwann Cells / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D057888:Iridoid Glucosides; C006650:aucubin; D017239:Paclitaxel