Analysis of the metabolic pathway by the administration of lipoid acid

• Project/Area Number: 26670310
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Epidemiology and preventive medicine
• Research Institution: Kanazawa University
• Principal Investigator: MATSUGO SEIICHI 金沢大学, 自然システム学系, 教授 (30148126)
• Co-Investigator(Kenkyū-buntansha): MIZUKAMI Tomoyuki 金沢大学, 理工研究域・自然システム学系, 助教 (80396811)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 抗酸化物質 / 顕微ラマンスペクトル / メタボローム / 包接化合物 / 代謝経路 / 光学異性体 / リポ酸 / 抗酸化ネットワーク / ラマンスペクトル / 細胞ストレス / S-S結合 / インスリン / 生体材料 / 特異性

Outline of Final Research Achievements

Alpha-lipoic acid (LA) is a very powerful antioxidant. LA has two enantiomers, R(+)-LA and S(-)-LA (S-LA), of which R-LA is naturally occurring and an essential cofactor in energy metabolism. it is quite vulnerable to physical stimuli such as heat or irradiation. The inclusion complex of LA is promising to overcome this weakness. We prepared the CD-LA inclusion complex and analyzed its stability and spectroscopic characteristics. Raman spectroscopy showed the characteristics for its high sensitivity to C-S and S-S bonds, which can be applied to other bio-materials (protein). Next, we examined the time-course metabolites levels in LA-treated rat hepatoma and evaluated the effect of R-LA and the enantioselectivity. This study indicated that R-LA treatment inhibited the glycolysis pathway, the lactic acid production and the Gly-Thr-Ser pathway and finally caused the inhibition of the gluconeogenesis.

Research Products

• [Int'l Joint Research] Christian-Albrechts-University(Germany)
• [Journal Article] Structural analysis of crystalline r(+)-α-lipoic acid-α-cyclodextrin complex based on microscopic and spectroscopic studies (2015)
  • Author(s): N. Ikuta, T. Endo, S. Hosomi, K. Setou, S. Tanaka, N. Ogawa, H. Yamamoto, T. Mizukami, S. Arai, M. Okuno, K. Takahashi, K. Terao, S. Matsugo
  • Journal Title: Int J Mol Sci. Volume: 16 Issue: 10 Pages: 24614-24628
  • DOI: 10.3390/ijms161024614
  • NAID: 120005689388
  • Peer Reviewed / Open Access
• [Journal Article] Spectroscopic Studies of R(+)-Alpha-Lipoic Acid – Cyclodextrin Complexes (2014)
  • Author(s): Naoko Ikuta, Akira Tanaka, Ayako Otsubo, Noriko Ogawa, Hiromitsu Yamamoto, Tomoyuki Mizukami, Shoji Arai, Masayuki Okuno, Keiji Terao and Seiichi Matsugo
  • Journal Title: International Journal of Molecular Science Volume: 15 Issue: 11 Pages: 20469-20485
  • DOI: 10.3390/ijms151120469
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] R-α lipoic acid γ-cyclodextrin complex increases energy expenditure: A 4-month feeding study in mice (2015)
  • Author(s): Naoko Ikuta, Sibylle Nikolai, Seiichi Matsugo, Gerald Rimbach, Keiji Terao
  • Organizer: 19th International Conference of FFC - 7th International Symposium of ASFFBC Functional and Medical Foods, Bioactive Compounds and Biomarkers: Longevity and Quality of Life
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2015-11-17
  • Int'l Joint Research
• [Presentation] Spectroscopic studies of R(+)-alpha lipoic acid - cyclodextrin complexes (2014)
  • Author(s): Naoko Ikuta, Akira Tanaka, Ayako Otsubo, Tomoyuki Mizukami, Shoji Arai, Masayuki Okuno, Keiji Terao, Seiichi Matsugo
  • Organizer: 17th International Cyclodextrin Symposium,
  • Place of Presentation: ザー ルブリュッケン（ドイツ）
  • Year and Date: 2014-05-29 – 2014-05-31