Mechanisms underlying large-leaf yellow tea mediated inhibition of cognitive impairment in the 5xFAD model of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia and is characterized by amyloid-ß (Aß) peptides and hyperphosphorylated Tau proteins. Evidence indicates that AD and type 2 diabetes mellitus (T2DM) share pathophysiological characteristics, including impaired insulin sensitivity. Large-leaf yellow tea (LYT) has been widely recognized for its health benefits, and we previously found that LYT can improve peripheral insulin resistance. PURPOSE: This study aimed to investigate the protective effects and underlying mechanisms of LYT in the 5xFAD mouse model of AD. METHODS: HPLC and spectrophotometric methods determined the chemical composition of the LYT extract. 5xFAD mice were treated with LYT supplementation (2 and 4 mg/ml) in drinking water for six months. Barnes and Y mazes were used to evaluate cognitive function, and the open field test assessed anxiety-like behavior. Immunofluorescence, silver, and Nissl staining were used to evaluate the pathological effects of LYT extract. A FRET-based assay assessed ß-site APP cleavage enzyme 1 (BACE1) activity, ELISA measured Aß levels in the brain, and Western blot analyses explored protein expression levels. RESULTS: Our results revealed that LYT significantly attenuated memory impairment and anxiety levels and alleviated cerebral neural damage. A reduction of senile plaques was also observed in both the cortex and hippocampus. LYT significantly inhibited the activity of BACE1, which resulted in a lower Aß protein level. In addition, LYT enhanced insulin receptor substrate 1 (IRS-1)-mediated phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), further suppressed glycogen synthase kinase-3ß (GSK3ß), and ultimately inhibited hyperphosphorylation of the protein Tau. The inhibitory effect of the LYT extract on the phosphorylation of Tau and BACE1 activity was dose-dependent. CONCLUSION: LYT improves cognitive ability and reduces Aß production by inhibiting BACE1 activity. Decreases of Tau protein hyperphosphorylation upon LYT treatment appear to be associated with the regulation of the IRS-1/PI3K/AKT/GSK3ß axis. Thus, the findings of this study also provide new evidence that LYT regulates insulin signaling pathways within the central nervous system.

Green Tea Suppresses Amyloid ß Levels and Alleviates Cognitive Impairment by Inhibiting APP Cleavage and Preventing Neurotoxicity in 5XFAD Mice.

SCOPE: The consumption of green tea is considered to be associated with a lower incidence of neurodegenerative diseases. In the present study, it is investigated the role of amyloid precursor protein cleavage, glial cell activation, neuroinflammation, and synaptic alterations in the protective effects of green tea against the amyloid ß (Aß) accumulation and cognitive impairment. METHODS AND RESULTS: 5XFAD mice are treated with green tea extract (GTE) for 8 or 16 weeks. Barnes maze and Y maze testing demonstrated that spatial learning and memory ability are markedly improved by GTE treatment. Immunofluorescence staining, ELISA, and western blot showed GTE significantly alleviate the formation of Aß and reduce the levels of sAPPß and C99, as well as sAPPα and C83. Meanwhile, GTE suppressed GFAP and Iba1 levels in the glial cells, increased PSD95 and synaptophysin levels in synaptic cells. Further, the IL-1ß level is decreased, RNA sequencing reveals the genes annotated in response to stimulus and immune response are regulated. CONCLUSION: Our findings indicate GTE suppresses Aß levels and alleviate cognitive impairment in 5XFAD mice. These beneficial effects are accompanied by inhibition of APP cleavage pathways, suppression of glial cell activation and pro-inflammatory responses, and a reduction of synapse loss.

Green tea polyphenols and epigallocatechin-3-gallate protect against perfluorodecanoic acid induced liver damage and inflammation in mice by inhibiting NLRP3 inflammasome activation.

Perfluorodecanoic acid (PFDA) is a highly toxic food contaminant that is extensively used in food applications as surface antifouling agent. In this present study, we aimed to assess whether green tea polyphenols (GTPs) and epigallocatechin-3-gallate (EGCG) exert protective effects against PFDA-induced liver damage and inflammation in mice. A mouse model to evaluate liver toxicity was established by giving mice drinking water containing different concentrations of PFDA. GTPs or EGCG (0.32%, w/v) were co-administered to mice exposed to PFDA in drinking water. Overall, GTPs and EGCG extended the survival time and inhibited weight loss among mice who received a lower dose of PFDA. Moreover, GTPs and EGCG ameliorated hepatic oxidative stress, cell apoptosis, necrosis, steatosis, edema, and degeneration, reduced hepatic inflammation and NLRP3 inflammasome activation caused by a moderate dose of PFDA. Taken together, these results show that GTPs or EGCG (or green tea intake) supplements can be beneficial for people exposed to PFDA.

Differences in chemical composition predictive of in vitro biological activity among commercially important cultivars of genus Camellia.

Leaves of plants from the genus Camellia (CAM) are used to make tea; however, there are limited data that compares chemical composition and biological activity of CAM cultivars used to make six tea types. Fourteen CAM cultivars were analyzed by HPLC and UPLC-Q-TOF-MS/MS and biological activity was assessed in a cell growth assay. Tea bioactives and cell growth inhibition varied 2-4 fold. EGCG was the dominant catechin that predicted the magnitude of growth inhibition. However, pure EGCG did not fully account for inhibitory activity suggesting that it may serve as a chemical marker for bioefficacy. As an unbiased characterization of differences in chemical composition among CAM, individual metabolomes were determined and used to generate principle components (PC). PC's from the metabolome were complementary to those from targeted analyses of tea bioactives and were predictive of growth inhibition. This study provides a frame work for identifying CAM cultivars with beneficial traits.

LC-MS-Based Metabolomics Reveals the Chemical Changes of Polyphenols during High-Temperature Roasting of Large-Leaf Yellow Tea.

Large-leaf yellow tea (LYT) is made from mature tea leaves with stems and has unique sensory characteristics different from other teas. To study the chemical changes of LYT during processing, samples were collected from each step for quantitative and qualitative analyses by high-performance liquid chromatography and liquid chromatography-mass spectrometry (LC-MS). LC-MS-based nontargeted and targeted metabolomics analyses revealed that the tea sample after roasting was markedly different from samples before roasting, with the levels of epicatechins and free amino acids significantly decreased, but the epimerized catechins increased dramatically. After accounting for common compounds in tea, N-ethyl-2-pyrrolidinone-substituted flavan-3-ols were found to be the marker compounds responsible for the classification of all samples, as they rapidly rose with increasing processing temperature. These findings suggested that the predominant changes in the tea constituents during large-leaf yellow tea roasting were the thermally induced degradation and epimerization of catechins and the formation of N-ethyl-2-pyrrolidinone-substituted flavan-3-ols from l-theanine.

Impact of Six Typical Processing Methods on the Chemical Composition of Tea Leaves Using a Single Camellia sinensis Cultivar, Longjing 43.

While the Camellia sinensis cultivar and processing method are key factors that affect tea flavor and aroma, the chemical changes in nonvolatile components associated with the tea processing method using a single cultivar of C. sinensis have not been reported. Fresh leaves from C. sinensis Longjing 43 were subjected to six tea processing methods and evaluated by targeted and untargeted chromatographic procedures. On the basis of targeted assessment of the total catechin content, three clusters were identified: yellow-green, oolong-white-dark, and black. However, principal component analysis of the total tea metabolome identified four chemical phenotypes: green-yellow, oolong, black-white, and dark. Differences in the non-catechin components included amino acids and γ-aminobutyric acid, which increased in white tea, and dihydroxyphenylalanine, valine, betaine, and theophylline, which increased in dark tea. Overall, this study identified a wide range of chemicals that are affected by commonly used tea processing methods and potentially affect the bioactivity of various tea types.

Differences in Chemical Composition among Commercially Important Cultivars of Genus Camellia.

Leaves from plants of the genus Camellia are used to make beverages and food products; however, there is limited data that compares the chemical composition of the unprocessed leaves of cultivars traditionally used to make these products. Plucked, fresh leaves from 14 commercially important cultivars were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. On the basis of assessment of 61 compounds that are known to be affected by postharvest tea processing methods, significant variation among unprocessed cultivar leaves was observed for compounds in five chemical classes: amino acids, catechins, flavonoids and flavone glycosides, phenolic acids, and alkaloids. These chemical differences were of sufficient magnitude to render two distinct chemically defined clusters of Camellia cultivars that did not reflect the traditional grouping of these cultivars based by species variant, tea type, or production region. Advanced statistical techniques identified candidate biomarkers for each chemical class to guide the development of comprehensive targeted analyses for constituents of biosynthetic pathways in which marked expression plasticity was observed. Targeted analyses of this type have the potential to identify Camellia species/cultivars that will facilitate the formulation of new beverages and designer foods with improved organoleptic characteristic and enhanced prebiotic or nutraceutical activity.

Exogenous transglutaminase improves multiple-stress tolerance in Lactococcus lactis and other lactic acid bacteria with glutamine and lysine in the cell wall.

OBJECTIVE: To increase the resistance of ingested bacteria to multiple environmental stresses, the role of transglutaminase in Lactococcus lactis and possible mechanisms of action were explored. RESULTS: L. lactis grown with transglutaminase exhibited significantly higher resistance to bile salts, stimulated gastric juice, antibiotics, NaCl, and cold stress compared to the control (cultured without transglutaminase), with no negative influence on cell growth. Transmission electron microscopy revealed that the cell walls of L. lactis cultured with 9 U transglutaminase/ml were approx. 1.9-times thicker than the control. Further analysis demonstrated that the multi-resistant phenotype was strain-specific; that is, it occurred in bacteria with the presence of glutamine and lysine in the peptidoglycan. CONCLUSION: Supplementation of culture media with transglutaminase is an effective, simple, and inexpensive strategy to protect specific ingested bacteria against multiple environmental challenges.