Yohei Tanimura1, Masato Yoshida2, Kan'ichiro Ishiuchi3, Masahiro Ohsawa4, Toshiaki Makino5. 1. Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya, 4678603, Japan. Electronic address: c132043@ed.nagoya-cu.ac.jp. 2. Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya, 4678603, Japan. Electronic address: vxv.be3al2si6o18.licht@gmail.com. 3. Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya, 4678603, Japan. Electronic address: ishiuchi@phar.nagoya-cu.ac.jp. 4. Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya, 4678603, Japan. Electronic address: ohsawa@phar.nagoya-cu.ac.jp. 5. Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya, 4678603, Japan. Electronic address: makino@phar.nagoya-cu.ac.jp.
Abstract
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.
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 murineperipheral 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 Aconitumalkaloids were measured. The contents of Aconitumalkaloids 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 Aconitumalkaloids. 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.