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Metabolic changes in the plasma of mild Alzheimer's disease patients treated with Hachimijiogan.
Kainuma, Mosaburo; Kawakatsu, Shinobu; Kim, Jun-Dal; Ouma, Shinji; Iritani, Osamu; Yamashita, Ken-Ichiro; Ohara, Tomoyuki; Hirano, Shigeki; Suda, Shiro; Hamano, Tadanori; Hieda, Sotaro; Yasui, Masaaki; Yoshiiwa, Aoi; Shiota, Seiji; Hironishi, Masaya; Wada-Isoe, Kenji; Sasabayashi, Daiki; Yamasaki, Sho; Murata, Masayuki; Funakoshi, Kouta; Hayashi, Kouji; Shirafuji, Norimichi; Sasaki, Hirohito; Kajimoto, Yoshinori; Mori, Yukiko; Suzuki, Michio; Ito, Hidefumi; Ono, Kenjiro; Tsuboi, Yoshio.
Affiliation
  • Kainuma M; Department of Japanese Oriental Medicine Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
  • Kawakatsu S; Aizu Medical Center, Department of Neuropsychiatry, Fukushima Medical University, Aizuwakamatsu, Japan.
  • Kim JD; Department of Research and Development, Division of Complex Biosystem Research (CBR), Institute of National Medicine (INM), University of Toyama, Toyama, Japan.
  • Ouma S; Department of Neurology, School of Medicine, Fukuoka University, Fukuoka, Japan.
  • Iritani O; Department of Geriatric Medicine, Kanazawa Medical University, Ishikawa, Japan.
  • Yamashita KI; Translational Neuroscience Center, Graduate School of Medicine, International University of Health and Welfare, Tochigi, Japan.
  • Ohara T; Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Hirano S; Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  • Suda S; Department of Psychiatry, Jichi Medical University, Tochigi, Japan.
  • Hamano T; Second Department of Internal Medicine, Division of Neurology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
  • Hieda S; Department of Medicine, Division of Neurology, Showa University School of Medicine, Tokyo, Japan.
  • Yasui M; Department of Neurology, Wakayama Medical University, Wakayama, Japan.
  • Yoshiiwa A; Department of General Medicine, Oita University Faculty of Medicine, Oita, Japan.
  • Shiota S; Department of General Medicine, Oita University Faculty of Medicine, Oita, Japan.
  • Hironishi M; Department of Internal Medicine, Wakayama Medical University Kihoku Hospital, Wakayama, Japan.
  • Wada-Isoe K; Department of Dementia Medicine, Kawasaki Medical School, Okayama, Japan.
  • Sasabayashi D; Department of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
  • Yamasaki S; Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
  • Murata M; Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
  • Funakoshi K; Department of Clinical Research Promotion, Kyushu University Hospital, Fukuoka, Japan.
  • Hayashi K; Department of Rehabilitation, Fukui Health Science University, Fukui, Japan.
  • Shirafuji N; Second Department of Internal Medicine, Division of Neurology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
  • Sasaki H; Second Department of Internal Medicine, Division of Neurology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
  • Kajimoto Y; Department of Internal Medicine, Wakayama Medical University Kihoku Hospital, Wakayama, Japan.
  • Mori Y; Department of Medicine, Division of Neurology, Showa University School of Medicine, Tokyo, Japan.
  • Suzuki M; Department of Neuropsychiatry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
  • Ito H; Department of Neurology, Wakayama Medical University, Wakayama, Japan.
  • Ono K; Department of Neurology, Kanazawa University Graduate School of Medical Sciences, Ishikawa, Japan.
  • Tsuboi Y; Department of Neurology, School of Medicine, Fukuoka University, Fukuoka, Japan.
Front Pharmacol ; 14: 1203349, 2023.
Article in En | MEDLINE | ID: mdl-37377927
ABSTRACT

Background:

Alzheimer's disease (AD), the most prevalent form of dementia, is a debilitating, progressive neurodegeneration. Amino acids play a wide variety of physiological and pathophysiological roles in the nervous system, and their levels and disorders related to their synthesis have been related to cognitive impairment, the core feature of AD. Our previous multicenter trial showed that hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), has an adjuvant effect for Acetylcholine estelase inhibitors (AChEIs) and that it delays the deterioration of the cognitive dysfunction of female patients with mild AD. However, there are aspects of the molecular mechanism(s) by which HJG improves cognitive dysfunction that remain unclear.

Objectives:

To elucidate through metabolomic analysis the mechanism(s) of HJG for mild AD based on changes in plasma metabolites.

Methods:

Sixty-seven patients with mild AD were randomly assigned to either an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI (HJG33, Control34). Blood samples were collected before, 3 months, and 6 months after the first drug administration. Comprehensive metabolomic analyses of plasma samples were done by optimized LC-MS/MS and GC-MS/MS methods. The web-based software MetaboAnalyst 5.0 was used for partial least square-discriminant analysis (PLS-DA) to visualize and compare the dynamics of changes in the concentrations of the identified metabolites.

Results:

The VIP (Variable Importance in Projection) score of the PLS-DA analysis of female participants revealed a significantly higher increase in plasma metabolite levels after HJG administration for 6 months than was seen in the control group. In univariate analysis, the aspartic acid level of female participants showed a significantly higher increase from baseline after HJG administration for 6 months when compared with the control group.

Conclusion:

Aspartic acid was a major contributor to the difference between the female HJG and control group participants of this study. Several metabolites were shown to be related to the mechanism of HJG effectiveness for mild AD.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Clinical_trials / Prognostic_studies Language: En Journal: Front Pharmacol Year: 2023 Document type: Article
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Clinical_trials / Prognostic_studies Language: En Journal: Front Pharmacol Year: 2023 Document type: Article