TY - JOUR
T1 - Metabolic changes in the plasma of mild Alzheimer’s disease patients treated with Hachimijiogan
AU - Kainuma, Mosaburo
AU - Kawakatsu, Shinobu
AU - Kim, Jun Dal
AU - Ouma, Shinji
AU - Iritani, Osamu
AU - yamashita, kenichiro
AU - Ohara, Tomoyuki
AU - Hirano, Shigeki
AU - Suda, Shiro
AU - Hamano, Tadanori
AU - Hieda, Sotaro
AU - Yasui, Masaaki
AU - Yoshiiwa, Aoi
AU - Shiota, Seiji
AU - Hironishi, Masaya
AU - Wada-Isoe, Kenji
AU - Sasabayashi, Daiki
AU - Yamasaki, Sho
AU - Murata, Masayuki
AU - Funakoshi, Kouta
AU - Hayashi, Kouji
AU - Shirafuji, Norimichi
AU - Sasaki, Hirohito
AU - Kajimoto, Yoshinori
AU - Mori, Yukiko
AU - Suzuki, Michio
AU - Ito, Hidefumi
AU - Ono, Kenjiro
AU - Tsuboi, Yoshio
N1 - Publisher Copyright:
Copyright © 2023 Kainuma, Kawakatsu, Kim, Ouma, Iritani, Yamashita, Ohara, Hirano, Suda, Hamano, Hieda, Yasui, Yoshiiwa, Shiota, Hironishi, Wada-Isoe, Sasabayashi, Yamasaki, Murata, Funakoshi, Hayashi, Shirafuji, Sasaki, Kajimoto, Mori, Suzuki, Ito, Ono and Tsuboi.
PY - 2023
Y1 - 2023
N2 - 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 (HJG:33, Control:34). 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.
AB - 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 (HJG:33, Control:34). 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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U2 - 10.3389/fphar.2023.1203349
DO - 10.3389/fphar.2023.1203349
M3 - Article
AN - SCOPUS:85163658036
SN - 1663-9812
VL - 14
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 1203349
ER -