OBJECTIVE: This systematic review analyzed the available evidence on (1) neurochemical changes; and (2) the relations between brain metabolite and validated cerebrospinal fluid biomarkers, and/or APOE in AD.
METHODS: PubMed, Cochrane, Scopus, and gray literature were systematically screened for studies deemed fit for the purpose of the current systematic review.
RESULTS: Twenty four articles met the inclusion criteria. Decreased levels of N-acetyl aspartate (NAA), NAA/(creatine) Cr, and NAA/(myo-inositol) ml, and increased ml, ml/Cr, Cho (choline)/Cr, and ml/NAA were found in the posterior cingulate cortex/precuneus. Increased ml is associated with increased tau levels, reduced NAA/Cr is associated with increased tau. ml/Cr is negatively correlated with Aβ42, and ml/Cr is positively correlated with t-tau. NAA and glutathione levels are reduced in APOE ε4 carriers. APOE ε4 exerts no modulatory effect on NAA/Cr. There is interaction between APOE ε4, Aβ42, and ml/Cr.
CONCLUSION: NAA, ml, NAA/Cr, NAA/ml and ml/Cr may be potentially useful biomarkers that may highlight functional changes in the clinical stages of AD. The combinations of ml and tau, NAA/Cr and Aβ42, and NAA/Cr and tau may support the diagnostic process of differentiating MCI/AD from healthy individuals. Large, longitudinal studies are required to clarify the effect of APOE ε4 on brain metabolites.
METHODS: Four different solvent extracts of OS, namely aqueous, ethanolic, 50% aqueous ethanolic and methanolic, at a dose of 500 mg/kg body weight (bw) were orally administered for 14 days to diabetic rats induced via intraperitoneal injection of 60 mg/kg bw STZ. NMR metabolomics approach using pattern recognition combined with multivariate statistical analysis was applied in the rat urine to study the resulted metabolic perturbations.
RESULTS: OS aqueous extract (OSAE) caused a reversal of DM comparable to that of 10 mg/kg bw glibenclamide. A total of 15 urinary metabolites, which levels changed significantly upon treatment were identified as the biomarkers of OSAE in diabetes. A systematic metabolic pathways analysis identified that OSAE contributed to the antidiabetic activity mainly through regulating the tricarboxylic acid cycle, glycolysis/gluconeogenesis, lipid and amino acid metabolism.
CONCLUSIONS: The results of this study validated the ethnopharmacological use of OS in diabetes and unveiled the biochemical and metabolic mechanisms involved.