ABSTRACT
Aging-induced cognitive impairment is associated with a loss of metabolic homeostasis and plasticity. An emerging idea is that targeting key metabolites is sufficient to impact the function of other organisms. Therefore, more metabolism-targeted therapeutic intervention is needed to improve cognitive impairment. We first conducted untargeted metabolomic analyses and 16S rRNA to identify the aging-associated metabolic adaption and intestinal microbiome change. Untargeted metabolomic analyses of plasma revealed L-arginine metabolic homeostasis was altered during the aging process. Impaired L-arginine metabolic homeostasis was associated with low abundance of intestinal Akkermansia muciniphila (AKK) colonization in mice. Long-term supplementation of AKK outer membranes protein-Amuc_1100, rescued the L-arginine level and restored cognitive impairment in aging mice. Mechanically, Amuc_1100 acted directly as a source of L-arginine and enriched the L-arginine-producing bacteria. In aged brain, Amuc_1100 promoted the superoxide dismutase to alleviated oxidation stress, and increased nitric oxide, derivatives of L-arginine, to improve synaptic plasticity. Meanwhile, L-arginine repaired lipopolysaccharide-induced intestinal barrier damage and promoted growth of colon organoid. Our findings indicated that aging-related cognitive impairment was closely associated with the disorders of L-arginine metabolism. AKK-derived Amuc_1100, as a potential postbiotic, targeting the L-arginine metabolism, might provide a promising therapeutic strategy to maintain the intestinal homeostasis and cognitive function in aging.
Subject(s)
Cognitive Dysfunction , Verrucomicrobia , Mice , Animals , RNA, Ribosomal, 16S , Homeostasis , ArginineABSTRACT
To identify candidate bacteria associated with aging, we performed fecal microbiota sequencing in young, middle-aged and older adults, and found lower Bifidobacterium adolescentis abundance in older individuals aged ≥60 years. Dietary supplementation of B. adolescentis improved osteoporosis and neurodegeneration in a mouse model of premature aging (Terc-/-) and increased healthspan and lifespan in Drosophila melanogaster and Caenorhabditis elegans. B. adolescentis supplementation increased the activity of the catalase (CAT) enzyme in skeletal muscle and brain tissue from Terc-/- mice, and suppressed cellular senescence in mouse embryonic fibroblasts. Transgenic deletion of catalase (ctl-2) in C. elegans abolished the effects of B. adolescentis on the lifespan and healthspan. B. adolescentis feeding also led to changes in oxidative stress-associated metabolites in Terc-/- mouse feces. These results suggest a role for B. adolescentis in improving the healthspan and lifespan through the regulation of CAT activity and host metabolism.
Subject(s)
Bifidobacterium adolescentis , Animals , Mice , Longevity , Caenorhabditis elegans/genetics , Catalase , Drosophila melanogaster , FibroblastsABSTRACT
The leaves of Hibiscus sabdariffa L. have been used as traditional folk medicines for treating high blood pressure and fever. There are many accessions of H. sabdariffa L. throughout the world. To assess the chemical variations of 31 different accessions of H. sabdariffa L., fingerprinting analysis and quantitation of major flavonoids were performed by high-performance liquid chromatography (HPLC). The HPLC method was validated for linearity, sensitivity, precision, repeatability and accuracy. A quadrupole-time-of-flight mass spectrometry (Q-TOF-MS) was applied for the characterization of major compounds. A total of 9 compounds were identified, including 6 flavonoids and 3 phenolic acids. In the fingerprint analysis, similarity analysis (SA) and principal component analysis (PCA) were used to differentiate the 31 accessions of H. sabdariffa L. Based on the results of PCA and SA, the samples No. 15 and 19 appeared much different from the main group. The total content of five flavonoids varied greatly among different accessions, ranging from 3.35 to 23.30 mg/g. Rutin was found to be the dominant compound and the content of rutin could contribute to chemical variations among different accessions. This study was helpful to understand the chemical variations between different accessions of H. sabdariffa L., which could be used for quality control. © 2015 The Authors Biomedical Chromatography Published by John Wiley & Sons Ltd.
Subject(s)
Flavonoids/analysis , Hibiscus/chemistry , Plant Leaves/chemistry , Chromatography, High Pressure Liquid/methods , Principal Component Analysis , Reference Standards , Reproducibility of ResultsABSTRACT
Hibiscus sabdariffa has gained attention for its antioxidant activity. There are many accessions of H. sabdariffa in the world. However, information on the quantification of antioxidant compounds in different accessions is rather limited. In this paper, a liquid chromatography/quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS) method for simultaneous determination of five antioxidant compounds (neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, rutin, and isoquercitrin) in H. sabdariffa leaves was developed. The method was validated for linearity, sensitivity, precision, repeatability and accuracy. The validated method has been successfully applied for determination of the five analytes in eight accessions of H. sabdariffa. The eight accessions of H. sabdariffa were evaluated for their antioxidant activities by DPPH free radical scavenging assay. The investigated accessions of H. sabdariffa were rich in rutin and exhibited strong antioxidant activity. The two accessions showing the highest antioxidant activities were from Cuba (No. 2) and Taiwan (No. 5). The results indicated that H. sabdariffa leaves could be considered as a potential antioxidant source for the food industry. The developed LC-Q-TOF-MS method is helpful for quality control of H. sabdariffa.