Effect of woohwangchungsimwon and donepezil co-treatment on cognitive function and serum metabolic profiles in a scopolamine-induced model of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Woohwangchungsimwon (WCW) is a traditional medicine used in East Asian countries to treat central nervous system disorders. Reported pharmacological properties include antioxidant effects, enhanced learning and memory, and protection against ischemic neuronal cell death, supporting its use in treating neurodegenerative diseases like Alzheimer's disease (AD). AIM OF THE STUDY: The study aims to assess the effects of co-treatment with WCW and donepezil on cognitive functions and serum metabolic profiles in a scopolamine-induced AD model. MATERIALS AND METHODS: Cell viability and reactive oxygen species (ROS) levels were measured in amyloid ß-peptide25-35 (Aß25-35)-induced SH-SY5Y cells. An AD model was established in ICR mice by intraperitoneal scopolamine administration. Animals underwent the step-through passive avoidance test (PAT) and Morris water maze (MWM) test. Hippocampal tissues were collected to examine specific protein expression. Serum metabolic profiles were analyzed using nuclear magnetic resonance (NMR) spectroscopy. RESULTS: Co-treatment with WCW and donepezil increased cell viability and reduced ROS production in Aß25-35-induced SH-SY5Y cells compared to that with donepezil treatment alone. Co-treatment improved cognitive functions and was comparable to donepezil treatment alone in the PAT and MWM tests. Pathways related to tyrosine, phenylalanine, and tryptophan biosynthesis, phenylalanine metabolism, and cysteine and methionine metabolism were altered by co-treatment. Levels of tyrosine and methionine, major serum metabolites in these pathways, were significantly reduced after co-treatment. CONCLUSIONS: Co-treatment with WCW and donepezil shows promise as a therapeutic strategy for AD and is comparable to donepezil alone in improving cognitive function. Reduced tyrosine and methionine levels after co-treatment may enhance cognitive function by mitigating hypertyrosinemia and hyperhomocysteinemia, known risk factors for AD. The serum metabolic profiles obtained in this study can serve as a foundation for developing other bioactive compounds using a scopolamine-induced mouse model.

Genome-wide comparative analyses of GATA transcription factors among seven Populus genomes.

GATA transcription factors (TFs) are widespread eukaryotic regulators whose DNA-binding domain is a class IV zinc finger motif (CX2CX17-20CX2C) followed by a basic region. We identified 262 GATA genes (389 GATA TFs) from seven Populus genomes using the pipeline of GATA-TFDB. Alternative splicing forms of Populus GATA genes exhibit dynamics of GATA gene structures including partial or full loss of GATA domain and additional domains. Subfamily III of Populus GATA genes display lack CCT and/or TIFY domains. 21 Populus GATA gene clusters (PCs) were defined in the phylogenetic tree of GATA domains, suggesting the possibility of subfunctionalization and neofunctionalization. Expression analysis of Populus GATA genes identified the five PCs displaying tissue-specific expression, providing the clues of their biological functions. Amino acid patterns of Populus GATA motifs display well conserved manner of Populus GATA genes. The five Populus GATA genes were predicted as membrane-bound GATA TFs. Biased chromosomal distributions of GATA genes of three Populus species. Our comparative analysis approaches of the Populus GATA genes will be a cornerstone to understand various plant TF characteristics including evolutionary insights.

Genome-wide comparative analyses of GATA transcription factors among 19 Arabidopsis ecotype genomes: Intraspecific characteristics of GATA transcription factors.

GATA transcription factors (TFs) are widespread eukaryotic regulators whose DNA-binding domain is a class IV zinc finger motif (CX2CX17-20CX2C) followed by a basic region. Due to the low cost of genome sequencing, multiple strains of specific species have been sequenced: e.g., number of plant genomes in the Plant Genome Database (http://www.plantgenome.info/) is 2,174 originated from 713 plant species. Thus, we investigated GATA TFs of 19 Arabidopsis thaliana genome-widely to understand intraspecific features of Arabidopsis GATA TFs with the pipeline of GATA database (http://gata.genefamily.info/). Numbers of GATA genes and GATA TFs of each A. thaliana genome range from 29 to 30 and from 39 to 42, respectively. Four cases of different pattern of alternative splicing forms of GATA genes among 19 A. thaliana genomes are identified. 22 of 2,195 amino acids (1.002%) from the alignment of GATA domain amino acid sequences display variations across 19 ecotype genomes. In addition, maximally four different amino acid sequences per each GATA domain identified in this study indicate that these position-specific amino acid variations may invoke intraspecific functional variations. Among 15 functionally characterized GATA genes, only five GATA genes display variations of amino acids across ecotypes of A. thaliana, implying variations of their biological roles across natural isolates of A. thaliana. PCA results from 28 characteristics of GATA genes display the four groups, same to those defined by the number of GATA genes. Topologies of bootstrapped phylogenetic trees of Arabidopsis chloroplasts and common GATA genes are mostly incongruent. Moreover, no relationship between geographical distribution and their phylogenetic relationships was found. Our results present that intraspecific variations of GATA TFs in A. thaliana are conserved and evolutionarily neutral along with 19 ecotypes, which is congruent to the fact that GATA TFs are one of the main regulators for controlling essential mechanisms, such as seed germination and hypocotyl elongation.