Mechanism of Astragalus mongholicus Bunge ameliorating cerebral ischemia-reperfusion injury: Based on network pharmacology analysis and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus Bunge (AMB) is a herb with wide application in traditional Chinese medicine, exerting a wealth of pharmacological effects. AMB has been proven to have an evident therapeutic effect on ischemic cerebrovascular diseases, including cerebral ischemia-reperfusion injury (CIRI). However, the specific mechanism underlying AMB in CIRI remains unclear. AIM OF THE STUDY: This study aimed to investigate the potential role of AMB in CIRI through a comprehensive approach of network pharmacology and in vivo experimental research. METHODS: The intersection genes of drugs and diseases were obtained through analysis of the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Gene Expression Omnibus (GEO) database. The protein-protein interaction (PPI) network was created through the string website. Meanwhile, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was carried out using R studio, and thereafter the key genes were screened. Then, the molecular docking prediction was made between the main active ingredients and target genes, and hub genes with high binding energy were obtained. In addition, molecular dynamic (MD) simulation was used to validate the result of molecular docking. Based on the results of network pharmacology, we used animal experiments to verify the predicted hub genes. First, the rat middle cerebral artery occlusion and reperfusion (MACO/R) model was established and the effective dose of AMB in CIRI was determined by behavioral detection and 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Then the target proteins corresponding to the hub genes were measured by Western blot. Moreover, the level of neuronal death was measured using hematoxylin and eosin (HE) and Nissl staining. RESULTS: Based on the analysis of the TCMSP database and GEO database, a total of 62 intersection target genes of diseases and drugs were obtained. The KEGG enrichment analysis showed that the therapeutic effect of AMB on CIRI might be realized through the advanced glycation endproduct-the receptor of advanced glycation endproduct (AGE-RAGE) signaling pathway in diabetic complications, nuclear factor kappa-B (NF-κB) signaling pathway and other pathways. Molecular docking results showed that the active ingredients of AMB had good binding potential with hub genes that included Prkcb, Ikbkb, Gsk3b, Fos and Rela. Animal experiments showed that AWE (60 g/kg) could alleviate CIRI by regulating the phosphorylation of PKCß, IKKß, GSK3ß, c-Fos and NF-κB p65 proteins. CONCLUSION: AMB exerts multi-target and multi-pathway effects against CIRI, and the underlying mechanism may be related to anti-apoptosis, anti-inflammation, anti-oxidative stress and inhibiting calcium overload.

Major depressive disorder: hypothesis, mechanism, prevention and treatment.

Worldwide, the incidence of major depressive disorder (MDD) is increasing annually, resulting in greater economic and social burdens. Moreover, the pathological mechanisms of MDD and the mechanisms underlying the effects of pharmacological treatments for MDD are complex and unclear, and additional diagnostic and therapeutic strategies for MDD still are needed. The currently widely accepted theories of MDD pathogenesis include the neurotransmitter and receptor hypothesis, hypothalamic-pituitary-adrenal (HPA) axis hypothesis, cytokine hypothesis, neuroplasticity hypothesis and systemic influence hypothesis, but these hypothesis cannot completely explain the pathological mechanism of MDD. Even it is still hard to adopt only one hypothesis to completely reveal the pathogenesis of MDD, thus in recent years, great progress has been made in elucidating the roles of multiple organ interactions in the pathogenesis MDD and identifying novel therapeutic approaches and multitarget modulatory strategies, further revealing the disease features of MDD. Furthermore, some newly discovered potential pharmacological targets and newly studied antidepressants have attracted widespread attention, some reagents have even been approved for clinical treatment and some novel therapeutic methods such as phototherapy and acupuncture have been discovered to have effective improvement for the depressive symptoms. In this work, we comprehensively summarize the latest research on the pathogenesis and diagnosis of MDD, preventive approaches and therapeutic medicines, as well as the related clinical trials.

Flavor perception and health benefits of tea.

As one of the most consumed non-alcoholic beverages in the world, tea is acclaimed for its pleasant flavor and various health benefits. Different types of tea present a distinctive flavor and bioactivity due to the changes in the composition and proportion of respective compounds. This article aimed to provide a more comprehensive understanding of tea flavor (including aroma and taste) and the character of tea in preventing and alleviating diseases. The recent advanced modern analytical techniques for revealing flavor components in tea, including enrichment, identification, quantitation, statistics, and sensory evaluation methodologies, were summarized in the following content. Besides, the role of tea in anti-cancer, preventing cardiovascular disease and metabolic syndrome, anti-aging and neuroprotection, and regulating gut microbiota was also listed in this article. Moreover, questions and outlooks were mentioned to objectify tea products' flavor quality and health benefits on a molecular level and significantly promote our understanding of the comprehensive value of tea as a satisfactory health beverage in the future.

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.

Analysis of Clinical and Pathological Features of Malignant Pulmonary Nodules.

Context: Early detection of pulmonary nodules in lung cancer and timely intervention can improve the number of diagnoses at early stages of lung cancer and can reduce mortality. At present, it's not possible to accurately determine the degree of pathological invasion of ground-glass nodules and the probability of regional lymph node metastasis using an imaging examination before surgery. Objective: The study intended to analyze the clinical, imaging, and pathological characteristics of malignant pulmonary nodules and to explore the high-risk factors for lymph node metastasis, using logistic regression multivariate analysis. Design: The research team retrospectively analyzed lung-cancer patients' demographic and clinical data. Setting: The study took place in the Department of Thoracic Surgery at Zhangzhou Municipal Hospital, affiliated with Fujian Medical University, in Zhangzhou, China. Participants: Participants were 1168 patients with malignant pulmonary nodules at the hospital between January 2018 and December 2020. Outcome Measures: The research team: (1) collected participant's pulmonary nodules after surgical resection, which the hospital had confirmed were primary lung cancer and (2) analyzed the clinical characteristics of the malignant pulmonary nodules using the World Health Organization's (WHO's) 2021 classification standard for lung-cancer tissue. The research team also collected participants' data, including gender, age, smoking status, nodular size, imaging characteristics, pathological type, degree of invasion, and lymph node metastasis, and analyzed the clinical characteristics of the malignant pulmonary nodules and explored the risk factors for lymph node metastasis. Results: Participants' average age was 56.79 ± 11.53 years, and the study included 675 females (57.79%) and 493 males (42.21%), 932 of whom didn't smoke (79.8%). Imaging indicated that most participants had nodules in the upper lobes of the lungs, 424 participants in the right lung (36.30%) and 303 in the left (25.94%). Imaging also showed that 400 participants had pure ground-glass nodules (34.25%) and 371 had solid nodules(31.76%), 355 had partial solid nodules (30.39%), the other 42 had cavitary nodules (3.60%) , and 1098 participants had adenocarcinoma (94.00%). Regarding the incidence of lymph node metastasis, 67 participants had N1 metastasis (5.74%) and 34 had N2 metastasis (2.91%). The multivariate logistic regression analysis showed that an increase in the nodular size (P < .001); the presence of lower-lobe pulmonary nodules, the nodular site (P = .025); and the amount of solid components in the nodule, the nodule's features (P < .001), were significant adverse factors for N1 lymph node metastasis, while gender, age, and smoking status didn't affect that outcome. Conclusions: Adenocarcinoma was the most common pathological type, and the probability of lymph node metastasis was low. N1 lymph node metastasis was associated with increased nodular size and solid components and the presence of lower lobe nodules.

Biomimetic Red Blood Cell Membrane-Mediated Nanodrugs Loading Ursolic Acid for Targeting NSCLC Therapy.

As one of the most common cancers worldwide, non-small-cell lung cancer (NSCLC) treatment always fails owing to the tumor microenvironment and resistance. UA, a traditional Chinese medicine, was reported to have antitumor potential in tumor models in vitro and in vivo, but showed impressive results in its potential application for poor water solubility. In this study, a novel biomimetic drug-delivery system based on UA-loaded nanoparticles (UaNPs) with a red blood cell membrane (RBCM) coating was developed. The RBCM-coated UANPs (UMNPs) exhibited improved water solubility, high stability, good biosafety, and efficient tumor accumulation. Importantly, the excellent antitumor efficiency of the UMNPs was confirmed both in vitro and in vivo in cancer models. In addition, we further investigated the antitumor mechanism of UMNPs. The results of Western blotting showed that UMNPs exerted an anticancer effect by inducing the apoptosis and autophagy of NSCLC cells, which makes it superior to free UA. In addition, body weight monitoring, hematoxylin and eosin (HE) analysis, and immunohistochemical (IHC) analysis showed no significant difference between UMNPs and the control group, indicating the safety of UMNPs. Altogether, the preparation of biomimetic UMNPs provides a promising strategy to improve outcomes in NSCLC.

Study on inhibition of Britannin on triple-negative breast carcinoma through degrading ZEB1 proteins.

BACKGROUND: Triple-negative breast carcinomas (TNBCs) are a breast carcinoma with the most aggressive form, which is demonstrated as enhanced invasion and recurrence. Britannin is extracted mainly from the traditional Chinese herb Inula japonica Thunb, and few studies have focused on its effect on TNBC. Moreover, there is still no report concerning the role of Britannin in degrading the transcripts of Zinc finger E-box-binding homeobox 1 (ZEB1) proteins. PURPOSE: To explore the potential effect of Britannin on invasion and stemness of TNBCs and its underlying mechanism. METHODS: Cellular activity was measured using MTT, and cell cycle was measured using flow cytometry (FCM). The effect of Britannin on the migrating and invading abilities of MDA-MB-231 and 4T1 cells were measured using the wound healing and transwell assays. The sizes and number of breast carcinoma cells were measured by tumor formation assay and in vitro limiting-dilution assay. CD44 expression in tumor spheroids was tested by immunofluorescence assay. Nextly, the expressions of epithelial-mesenchymal transition (EMT) markers and ZEB1 protein expressional level were detected by western blot . ZEB1 mRNA expressional level was analyzed using RT-qPCR. Drug affinity-responsive target stability (DARTS) method was used to detect the binding activity between Britannin and ZEB1. Co-immunoprecipitation (Co-IP) analysis was applied to test the ubiquitination of ZEB1. The mouse models for experimental lung metastasis of 4T1 cells were established to detect the anti-metastasis effect of Britannin in vivo, and the expressional levels of EMT markers in lung metastases were detected by immunohistochemistry. RESULTS: Britannin could inhibit cell growth and G2/M arrest in TNBC cells. Britannin could inhibit the migrating and invading ability without inducing severe apoptosis of MDA-MB-231 and 4T1 cells. Meanwhile, Britannin reduced the size and number of spheroids formed in these two cells, and decreased the expressional level of stem cells biomarker CD44 in tumor spheroids. Mechanism research showed that Britannin specifically bound to ZEB1 and induced its ubiquitination in MDA-MB-231 cells. Afterwards, Britannin disturbed protein stability and promoted ZEB1 protein degradation. Importantly, Britannin could not inhibit cell invasion and spheroid formation after ZEB1 expression was knocked down. Finally, Britannin inhibition of 4T1 cell metastasis was confirmed through establishing mouse models for the experimental lung metastasis. It was proved that both Britannin and paclitaxel could decrease the lung metastases, and Britannin could also down-regulate the protein expressional levels of ZEB1, MMP9 and CD44. CONCLUSION: This study reveals that Britannin suppresses the invasion and metastasis of TNBC cells through degrading ZEB1, which suggests that Britannin can be used to prevent tumor metastasis and recurrence via degrading ZEB1proteins.

The interplay between audiovisual temporal synchrony and semantic congruency in the cross-modal boost of the visual target discrimination during the attentional blink.

The visual attentional blink can be substantially reduced by delivering a task-irrelevant sound synchronously with the second visual target (T2), and this effect is further modulated by the semantic congruency between the sound and T2. However, whether the cross-modal benefit originates from audiovisual interactions or sound-induced alertness remains controversial, and whether the semantic congruency effect is contingent on audiovisual temporal synchrony needs further investigation. The current study investigated these questions by recording event-related potentials (ERPs) in a visual attentional blink task wherein a sound could either synchronize with T2, precede T2 by 200 ms, be delayed by 100 ms, or be absent, and could be either semantically congruent or incongruent with T2 when delivered. The behavioral data showed that both the cross-modal boost of T2 discrimination and the further semantic modulation were the largest when the sound synchronized with T2. In parallel, the ERP data yielded that both the early occipital cross-modal P195 component (192-228 ms after T2 onset) and late parietal cross-modal N440 component (424-448 ms) were prominent only when the sound synchronized with T2, with the former being elicited solely when the sound was further semantically congruent whereas the latter occurring only when that sound was incongruent. These findings demonstrate not only that the cross-modal boost of T2 discrimination during the attentional blink stems from early audiovisual interactions and the semantic congruency effect depends on audiovisual temporal synchrony, but also that the semantic modulation can unfold at the early stage of visual discrimination processing.

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.

Black Tea Quality is Highly Affected during Processing by its Leaf Surface Microbiome.

Microbiomes can greatly affect the quality of fermented food and beverages, including tea. In this study, microbial populations were characterized during black and green tea manufacturing, revealing that tea processing steps can drive both the bacterial and fungal community structure. Tea leaves were found to mostly harbor Proteobacteria, Bacteriodetes, Firmicutes, and Actinobacteria among bacteria and Ascomycetes among fungi. During processing, tea microbial populations changed especially between sterilized and unsterilized samples. The surface sterilization of fresh leaves before processing can remove many microbes, especially the bacteria of the genera Sphingomonas and Methylobacteria, indicating that these are mostly phylloplane microbes on tea leaves. The surface sterilization removed most fungi, except the Debaryomyces. We also observed a fluctuation in the content of several tea quality-related metabolites during processing. Caffeine and theanine were found in the same quantities in green tea with or without leaf surface sterilization. However, the sterilization process dramatically decreased the content of total catechins and theanine in black tea, indicating that microbes on the surface of tea leaf may be involved in maintaining the formation of these important metabolites during black tea processing.

Yellow Tea Stimulates Thermogenesis in Mice through Heterogeneous Browning of Adipose Tissues.

SCOPE: Large-leaf yellow tea (YT) exhibits interesting beneficial metabolic effects in previous studies. Here, the authors elucidated the actions of YT on thermogenesis, energy metabolism, and adipocyte metabolic conversion. METHODS AND RESULTS: Five-week-old male C57BL/6 mice are fed low-fat diet, high-fat diet (HFD), and HFD supplemented with 0.5% or 2.5% YT. After treatment for 10 or 14 weeks, YT enhances energy expenditure, O2 consumption and CO2 production. YT strongly boosts thermogenic program in brown adipose tissue (BAT) and subcutaneous adipose tissue (SAT), while only weakly in epididymal adipose tissue (EAT). These are accompanied by higher body temperature, increased mitochondrial copy numbers, and upregulation of thermogenic genes (Ucp1, Pgc1α, etc.) and proteins. The classic brown adipocyte markers (Eva1, Zic1) are induced only in BAT, while beige adipocyte markers (Tbx1, Tmem26) are boosted only in SAT. Furthermore, subcutaneous-originated preadipocytes are induced by YT in vitro to differentiate to brown-like adipocytes - a browning effect. CONCLUSION: Dietary YT induces adaptive thermogenesis through increasing mitochondrial biogenesis in EAT, inducing beigeing in SAT and enhancing browning in the BAT.

Neural Basis of Semantically Dependent and Independent Cross-Modal Boosts on the Attentional Blink.

The present study recorded event-related potentials (ERPs) in a visual object-recognition task under the attentional blink paradigm to explore the temporal dynamics of the cross-modal boost on attentional blink and whether this auditory benefit would be modulated by semantic congruency between T2 and the simultaneous sound. Behaviorally, the present study showed that not only a semantically congruent but also a semantically incongruent sound improved T2 discrimination during the attentional blink interval, whereas the enhancement was larger for the congruent sound. The ERP results revealed that the behavioral improvements induced by both the semantically congruent and incongruent sounds were closely associated with an early cross-modal interaction on the occipital N195 (192-228 ms). In contrast, the lower T2 accuracy for the incongruent than congruent condition was accompanied by a larger late occurring cento-parietal N440 (424-448 ms). These findings suggest that the cross-modal boost on attentional blink is hierarchical: the task-irrelevant but simultaneous sound, irrespective of its semantic relevance, firstly enables T2 to escape the attentional blink via cross-modally strengthening the early stage of visual object-recognition processing, whereas the semantic conflict of the sound begins to interfere with visual awareness only at a later stage when the representation of visual object is extracted.

Black and Green Tea Supplements Ameliorate Male Infertility in a Murine Model of Obesity.

Obesity, a chronic metabolic disorder, can affect male reproductive function. As a functional beverage, tea has many biological activities and potential in the treatment of obesity. However, its effects on male reproductive damage induced by obesity are not yet clear. In this study, a murine model of obesity was established by feeding with high-fat diet (HF). A total of 24 male mice were divided into four groups: normal diet (control), HF, HF supplemented with 5% green tea powder (HF+G), and HF supplemented with 5% black tea powder (HF+B). The results showed that the HF + B significantly reduced the mouse body weight gain and testicular coefficient and lowered the serum insulin and leptin levels compared with the HF group. The sperm malformation rate of mice in the HF group had a significant increase when compared with the control group, the HF + B group had a significant decrease compared with the HF group, and no difference from the control group. The HF + G and HF + B significantly increased testosterone levels in serum compared with the HF group. The testosterone production-related gene cytochrome P450 family 11 subfamily a member (CYP11A1) and cytochrome p450 family 17 subfamily a member 1 (CYP17A1) expressions in testis were significantly increased in the HF + G group compared with HF group. In addition, the HF + G and HF + B abolished the effects of HF on superoxide dismutase (SOD), malondialdehyde, and glutathione levels in testis and antioxidant-related gene expressions of XRCC1 and SOD1. Overall, our findings have provided evidence that black and green tea has a positive effect on reducing reproductive damage in a male murine model of obesity, and that black tea is more effective than green tea.

Green tea polyphenol epigallocatechin-3-gallate alleviates nonalcoholic fatty liver disease and ameliorates intestinal immunity in mice fed a high-fat diet.

Green tea polyphenol epigallocatechin-3-gallate (EGCG) may help prevent metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanisms of its protective effects are complicated and remain unclear. With the gut-liver axis theory as a foundation, the present study investigated the effects of EGCG on intestinal mucosal immunity in male C57BL/6 mice fed a high-fat Western diet or the diet supplemented with 0.4% dietary EGCG (w/w) for 14 weeks. Dietary EGCG supplementation effectively prevented changes-including excessive accumulation of visceral and hepatic fat, abnormal liver function, and elevated concentrations of serum and liver inflammatory cytokines-known to be caused by high-fat diets. In addition, serum lipopolysaccharide concentrations decreased by 94.3%. RNA sequencing data of differentially expressed genes in ileal samples among three groups indicated that most of the pathways in the Kyoto Encyclopedia of Genes and Genomes in the first 20 enrichment levels were related to immunity and inflammatory reactions. Real-time reverse transcription quantitative polymerase chain reaction was used to determine alterations in expression levels of key genes related to intestinal immune function and inflammatory responses from ileal and colonic samples. Changes in secretory immunoglobulin A in the small intestine, serum, and feces further demonstrated improved intestinal mucosal immunity in the EGCG-treated mice. In conclusion, dietary EGCG effectively prevented the development of NAFLD and significantly improved intestinal mucosal immunity in mice with obesity induced by a high-fat diet. However, whether improved intestinal immune function is the key mechanism underlying the health benefits of dietary EGCG warrants further research.

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.

Multivariate effects of Chinese keemun black tea grades (Camellia sinensis var. sinensis) on the phenolic composition, antioxidant, antihemolytic and cytotoxic/cytoprotection activities.

The main objectives of the study were to compare the phenolic composition, chemical and biological antioxidant activities, and cytotoxicity towards IMR90, HCT8, and A549 cell lines of eight grades of Chinese keemun black tea (Camellia sinensis var. sinensis) using a statistical approach. No cytotoxic effects were observed on IMR90 normal cells. Our results all together show that the chemical antioxidant capacity of high-grade black teas measured by DPPH, FRAP, and total reducing capacity assays was correspondingly higher than the mean values of low-grade teas and these antioxidant assays were not associated with cytotoxicity towards cancerous cell lines (HCT8 and A549). High grades of Chinese keemun black teas contained higher contents of total phenolics, flavonoids and ortho-diphenols than lower grades and theaflavin-3,3'-di-gallate could only be detected in high black tea grades (T1 and T2). Intermediate-high keemun black tea grades - C1, C3, T1, and T2 - which also had the highest mean values of TPC, flavonoids, o-diphenols, theaflavin-3-gallate, theaflavin-3'-gallate, Fe2+ chelating ability, and chemical antioxidant activity, presented the highest inhibition of Wistar rat's brain oxidation. No clear differentiation and trend were observed between erythrocyte protection and Chinese black tea grades as results clearly showed that intermediate black tea grades (C3 and C4) protected more the human erythrocytes against mechanical stress. Our study shows that although higher Chinese keemun black tea grades (T1 and T2) presented the highest TPC, flavonoids, and chemical antioxidant activity, these in vitro chemical assays were not translated into higher biological activity.

Green tea polyphenols prevent lipopolysaccharide-induced inflammatory liver injury in mice by inhibiting NLRP3 inflammasome activation.

Inflammatory liver diseases present a significant public health problem. Green tea polyphenols (GTPs) have a myriad of health benefits in animals and humans, including alleviating of hepatic inflammation; however, the underlying mechanisms are complicated and remain unclear. The current study investigated the preventive effects and mechanism of GTPs on lipopolysaccharide (LPS)-induced inflammatory liver injury in mice. The ICR mice received intragastric GTPs once per day for 7 consecutive days prior to LPS stimulation (15 mg kg-1, intraperitoneally) and liver damage and oxidative stress, pro-inflammatory cytokines, and the hepatic nuclear factor-κB (NF-κB) and Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasomes were observed. Our results showed that GTP supplementation significantly reduced LPS-induced plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and hepatic malondialdehyde (MDA) levels; and LPS-induced reduction of glutathione (GSH) levels and total superoxide dismutase (T-SOD) activities was drastically improved by GTP pretreatment. GTP supplementation significantly reduced plasma contents and hepatic mRNA levels of interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor (TNF)-α, compared with LPS-treated mice which did not receive GTP treatment. In addition, the production of cytokines, such as IL-1ß, IL-18, IL-6, and TNF-α in mice livers, and acute-phase response (plasma levels of nitric oxide and C-reactive protein) were also decreased following GTP pre-treatment. Furthermore, GTPs reduced LPS-induced hepatic NF-κB signaling and NLRP3 inflammasome activation. GTPs exert protective effects against inflammatory liver injury by regulating NF-κB signaling and the NLRP3 inflammasome activation. Our findings suggest that dietary GTP supplementation may be an adjunctive prevention and treatment for acute liver injury-associated inflammation.

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.

Characterization of Brazilian coffee based on isotope ratio mass spectrometry (δ13C, δ18O, δ2H, and δ15N) and supervised chemometrics.

Authentication of ground coffee has become an important issue because of fraudulent activities in the sector. In the current work, sixty-seven Brazilian coffees produced in different geographical origins using organic (ORG, n = 25) and conventional (CONV, n = 42) systems were analyzed for their stable isotope ratios (δ13C, δ18O, δ2H, and δ15N). Data were analyzed by inferential analysis to compare the factors whereas linear discriminant analysis (LDA), k-nearest neighbors (k-NN), and support vector machines (SVM) were used to classify the coffees based on their origin. ORG and CONV cultivated coffees could not be differentiated according to C stable isotope ratio (δ13C; p = 0.204), but ORG coffees presented higher values of the N stable isotope ratio (δ15N; p = 0.0006). k-NN presented the best classification results for both ORG and CONV coffees (87% and 67%, respectively). SVM correctly classified coffees produced in São Paulo (75% accuracy), while LDA correctly classified 71% of coffees produced in Minas Gerais.