title: Processed aconite root and its active ingredient neoline may alleviate oxaliplatin-induced peripheral neuropathic pain.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  We investigated the effects of PA on L-OHP-induced peripheral neuropathies and identified the active ingredient within PA extract.
  
  
  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.
authors.affiliation: Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya 467-8603, Japan; Department of Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya 464-8601, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Miyamoto
authors.affiliation: Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Yokoyama
authors.affiliation: Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Sugi
authors.affiliation: Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Akina
authors.initials: A
authors.lastname: Kagioka
authors.affiliation: Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kitao
authors.affiliation: Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Adachi
authors.affiliation: Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya 467-8603, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ohsawa
authors.affiliation: Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya 467-8603, Japan; The Kochi Prefectural Makino Botanical Garden, Kochi 781-8125, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Mizukami
authors.affiliation: Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya 467-8603, Japan. Electronic address: makino@phar.nagoya-cu.ac.jp.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Makino
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D031841:Aconitum / Q000737:chemistry*; D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D006930:Hyperalgesia / Q000139:chemically induced* / Q000188:drug therapy; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000633:toxicity*; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000188:drug therapy; D008517:Phytotherapy
chemical_list: D000700:Analgesics; D009944:Organoplatinum Compounds; C487396:neoline; D000077150:Oxaliplatin; D000157:Aconitine
keywords: Dorsal root ganglion; Neoline; Oxaliplatin; Peripheral neuropathies; Processed aconite root