2. Academic Validation
  3. Neoline, an active ingredient of the processed aconite root in Goshajinkigan formulation, targets Nav1.7 to ameliorate mechanical hyperalgesia in diabetic mice

Neoline, an active ingredient of the processed aconite root in Goshajinkigan formulation, targets Nav1.7 to ameliorate mechanical hyperalgesia in diabetic mice

  • J Ethnopharmacol. 2020 Sep 15;259:112963. doi: 10.1016/j.jep.2020.112963.
Yoshihiko Nakatani 1,  Kanako Negoro 2,  Miki Yamauchi 3,  Maki Katasho 4,  Kei-Ichiro Ishikura 5,  Anna Iwaki 6,  Kazuyo Tsukada 7,  Marina Yamaguchi 8,  Arata Uehara 9,  Masato Yoshida 10,  Kan'ichiro Ishiuchi 11,  Toshiaki Makino 12,  Masaki Kitajima 13,  Masahiro Ohsawa 14,  Taku Amano 15
Affiliations

Affiliations

  • 1 Department of Pharmacotherapeutics, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan; Advanced Education and Research Center for Kampo Medicine, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan. Electronic address: ynakatani@iuhw.ac.
  • 2 Department of Pharmacotherapeutics, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan. Electronic address: goronekanako@gmail.com.
  • 3 Department of Pharmacotherapeutics, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan. Electronic address: sw_clover_en@icloud.com.
  • 4 Department of Pharmacotherapeutics, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan. Electronic address: prism_ksgh@icloud.com.
  • 5 Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan. Electronic address: c162703@ed.phar.nagoya-cu.ac.jp.
  • 6 Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan. Electronic address: c182704@ed.phar.nagoya-cu.ac.jp.
  • 7 Department of Pharmacotherapeutics, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan. Electronic address: 1031145@g.iuhw.ac.jp.
  • 8 Department of Pharmacotherapeutics, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan. Electronic address: 1231179@g.iuhw.ac.jp.
  • 9 Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan. Electronic address: 1331023@g.iuhw.ac.jp.
  • 10 Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan. Electronic address: vxv.be3al2si6o18.licht@gmail.com.
  • 11 Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan. Electronic address: ishiuchi@phar.nagoya-cu.ac.jp.
  • 12 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.
  • 13 International University of Health and Welfare, Tokyo Office, Amity-Nogizaka-BIdg 1-24-1 Minamiaoyama, Minato-ku, Tokyo, 107-0062, Japan.
  • 14 Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan. Electronic address: ohsawa@phar.nagoya-cu.ac.jp.
  • 15 Department of Pharmacotherapeutics, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan; Advanced Education and Research Center for Kampo Medicine, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan. Electronic address: amano-pharmacothera@iuhw.ac.jp.
PMID: 32439405 DOI: 10.1016/j.jep.2020.112963
Abstract

Ethnopharmacological relevance: Goshajinkigan (GJG), a traditional Japanese Kampo formula, has been shown to exhibit several pharmacological actions, including antinociceptive effects. Processed aconite root (PA), which is considered to be an active ingredient of GJG, has also been demonstrated to have an ameliorative effect on pain, such as diabetic peripheral neuropathic pain. We recently identified neoline as the active ingredient of both GJG and PA that is responsible for its effects against oxaliplatin-induced neuropathic pain in mice.

Aim of the study: In the present study, we investigated whether GJG, PA, and neoline could inhibit Nav1.7 voltage-gated Sodium Channel (VGSC) current and whether neoline could ameliorate mechanical hyperalgesia in diabetic mice.

Materials and methods: To assess the electrophysiological properties of GJG extract formulation, powdered PA, and neoline on Nav1.7 VGSCs, whole-cell patch clamp recording was performed using human HEK293 cells expressing Nav1.7 VGSCs. In addition, the ameliorative effects of neoline on diabetic peripheral neuropathic pain were evaluated using the von Frey test in streptozotocin (STZ)-induced diabetic model mice.

Results: GJG extract formulation significantly inhibited Nav1.7 VGSC peak current. Powdered PA also inhibited Nav1.7 VGSC peak current. Like GJG and PA, neoline could inhibit Nav1.7 VGSC current. When diabetic mice were treated with neoline by intraperitoneal acute administration, the mechanical threshold was increased in diabetic mice, but not in non-diabetic mice, in a behavioral study.

Conclusion: These results suggest that neoline might be a novel active ingredient of GJG and PA that is one of responsible ingredients for ameliorating mechanical hyperalgesia in diabetes via the inhibition of Nav1.7 VGSC current at least.

Keywords

Diabetic mice; Goshajinkigan; Nav1.7; Neoline; Processed aconite root; Voltage-gated sodium channel.

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