Taxifolin retards the D-galactose-induced aging process through inhibiting Nrf2-mediated oxidative stress and regulating the gut microbiota in mice.

Aging and aging-related metabolic complications are global problems that seriously threaten public health. Taxifolin (TAX) is a novel health food and has been widely proved to have a variety of biological activities used in food and medicine. However, the delayed effect of TAX on the aging process has not been investigated. The purpose of this study is to explore the role of TAX as a natural active substance on aging brain tissue induced by D-galactose (D-Gal) and to determine the effect of supplementing TAX on the metabolism of the intestinal flora in aging bodies. The aging model was established by intraperitoneal injection of D-Gal (800 mg kg-1) once per 3 days for 12 weeks, and TAX (20 and 40 mg kg-1) was administered daily by oral gavage after 6 weeks of induction with D-Gal. After testing aging mice in an eight-arm maze, the results showed that TAX treatment significantly restored spatial learning and memory impairment. Moreover, long-term D-Gal treatment incited cholinergic dysfunction of aging mice, and H&E staining revealed obvious histopathological damage and structural disorder in the hippocampus of mouse brain tissue, while TAX treatment significantly reversed these changes. Importantly, supplementing with TAX significantly mitigated oxidative stress injury by alleviating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) while increasing antioxidant enzymes. Furthermore, TAX decreased the apoptosis of the aging brain by regulating the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and activating nuclear factor-erythroid 2-related factor 2 (Nrf2), nuclear heme oxygenase-1 (HO-1), and NADH dehydrogenase quinone 1 (NQO1) to maximally moderate the oxidative stress injury that occurred after D-Gal induction. In addition, 16S rDNA analysis revealed that TAX treatment decelerated the D-gal-induced aging process by regulating the composition of the intestinal flora and abundance of beneficial bacteria, including Enterorhabdus, Clostridium, Bifidobacterium, and Parvibacter. In conclusion, the results of this study demonstrated that TAX alleviated oxidative stress injury in mice aged by D-Gal and also confirmed that TAX improved the aging process by regulating intestinal microbes, which provides the possibility of prevention and treatment for aging and metabolic disorders through the potential food health factors.

Weighted gene co-expression network analysis identifies specific modules and hub genes related to Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) is one of the most common neurodegenerative diseases. This study aims to screen specific modules and key genes related to PD. METHODS: Gene expression profile data GSE6613 and GSE22491 were downloaded from the Gene Expression Omnibus database. The significantly differentially expressed genes (DEGs) in different datasets were screened, followed by gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The Weighted Gene Co-expression Network Analysis (WGCNA) was used to screen disease-related modules that are significantly stable across datasets. The protein-protein interaction network was constructed using the DEGs in the stable module obtained and preservation modules. Finally, the hub genes directly related to PD were screened. RESULTS: A total of 179 DEGs with the same significant difference direction were screened. The enrichment analysis of GO and KEGG pathways showed that 20 significantly related GO biological processes and 9 KEGG signaling pathways were screened. A total of three highly conservative modules were detected in the WGCNA network. Finally, three significant PD-related KEGG pathways screened from the Comparative Toxicogenomics Database were identified, including neuroactive ligand-receptor interaction (CRHR2, CTSG, GRIN1, GRIN2D, LPAR4 and P2RX3), amyotrophic lateral sclerosis (BCL2, GRIN1 and GRIN2D) and alcoholism (CAMKK2, GRIN1, GRIN2D and SLC18A2). Key genes, such as SLC18A2, GRIN1 and GRIN2D, may be potential candidate genes for PD progression. CONCLUSIONS: Our findings indicate that SLC18A2, GRIN1 and GRIN2D may play an important role in the pathogenesis of PD.

Arginyl-fructosyl-glucose, a Major Maillard Reaction Product of Red Ginseng, Attenuates Cisplatin-Induced Acute Kidney Injury by Regulating Nuclear Factor κB and Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathways.

Recently, although ginseng ( Panax ginseng C. A. Meyer) and its main component saponins (ginsenosides) have been reported to exert protective effects on cisplatin (CDDP)-induced acute kidney injury (AKI), the beneficial activities of non-saponin on CDDP-induced AKI is little known. This research was designed to explore the protective effect and underlying mechanism of arginyl-fructosyl-glucose (AFG), a major and representative non-saponin component generated during the process of red ginseng, on CDDP-caused AKI. AFG at doses of 40 and 80 mg/kg remarkably reversed CDDP-induced renal dysfunction, accompanied by the decreased levels of serum creatinine and blood urea nitrogen. Interestingly, all of oxidative stress indices were ameliorated after pretreatment with AFG continuously for 10 days. Importantly, AFG relieved CDDP-induced inflammation and apoptosis in part by mitigating the cascade initiation steps of nuclear factor κB signals and regulating the participation of the phosphatidylinositol 3-kinase/protein kinase B signal pathway. In conclusion, these results clearly provide strong rationale for the development of AFG to prevent CDDP-induced AKI.