It has been proposed that the gut microbiome may be related to obesity, and diet-induced obesity may induce changes in the gut microbiota composition. Our previous studies suggested that persimmon tannin (PT), which is highly polymerized and non-absorbable in the intestine, showed anti-hyperlipidemic and cholesterol-lowering effects in animal models. Considering that the possible composition modification effects of PT on intestinal bacteria might contribute to its anti-hyperlipidemic and cholesterol-lowering effects in vivo, in this study, we determined whether the PT administration could modify the gut microbiota in both normal diet-fed and high-cholesterol (HC) diet-fed rats, and how PT altered the bacterial composition in both normal and HC fed rats. Sprague-Dawley rats were randomly divided into eight groups, and fed with either a normal or an HC diet supplemented with or without a low/medium/high dose of PT (50 (LPT), 100 (MPT), 200 (HPT) mg per kg body weight (BW) per day, respectively) for 4 weeks. On days 0, 7, 14, 21 and 28, feces were collected and prepared for the microbiota and physicochemical analysis. The results showed that LPT and MPT supplementation significantly altered the gut microbiota composition by increasing the Bacteroidetes/Proteobacteria ratio in both normal diet-fed and HC diet-fed rats. LPT also decreased the Firmicutes/Bacteroidetes ratio in normal diet-fed rats and MPT decreased the Firmicutes/Bacteroidetes ratio in HC diet-fed rats. Both LPT and MPT supplementation induced a significant alteration in specific bacterial species after 14 days of treatment. The relative abundance of Bifidobacterium sp. and Lactobacillus sp. was increased by both LPT and MPT treatment, and that of Escherichia coli and Enterococcus was reduced. Our data also indicate that there is a correlation between the changes in bacterial composition and the changes in short-chain fatty acid (SCFA) metabolism. However, HPT supplementation altered the gut microbiota at the phylum and species levels in an adverse way.

BackgroundHydrogen peroxide (H2O2)-based tooth bleaching reagents have recently increased in popularity and controversy. H2O2 gel (3%) is used in a Nightguard for vital bleaching; transient tooth sensitivity and oral mucosa irritation have been reported. Genotoxicity and carcinogenicity have also been significant concerns.MethodsWe used primary cultured normal human oral keratinocytes (NHOKs) as an in vitro model to investigate the pathological effects to mitochondria functions on human oral keratinocytes exposed to different doses of H2O2 for different durations.ResultsAn MTT assay showed compromised cell viability at a dose over 5 mM. The treatments induced nuclear DNA damage, measured using a single-cell gel electrophoresis assay. A real-time quantitative polymerase chain reaction showed H2O2 induced significant increase in mitochondrial 4977-bp deletion. Mitochondrial membrane potential and apoptosis assays suggested that oxidative damage defense mechanisms were activated after prolonged exposure to H2O2. Reduced intracellular glutathione was an effective defense against oxidative damage from 5 mM of H2O2.ConclusionOur study suggests the importance for keratinocyte damage of the dose and the duration of the exposure to H2O2 in at-home-bleaching. A treatment dose ≥100 mM directly causes severe cytotoxicity with as little as 15 min of exposure.

No abstract

Current therapies for ischemic stroke are insufficient due to the lack of specific drugs. This study aimed to investigate the protective activity of polyphenol extracts from Terminalia chebula against cerebral ischemia-reperfusion induced damage. Polyphenols of ethyl acetate and n-butanol fractions were extracted from T. chebula. BV2 microglial cells exposed to oxygen-glucose deprivation/reoxygenation and mice subjected to middle cerebral artery occlusion/reperfusion were treated by TPE and TPB. Cell viability, cell morphology, apoptosis, mitochondrial membrane potential, enzyme activity and signaling pathway related to oxidative stress were observed. We found that TPE and TPB showed strong antioxidant activity in vitro. The protective effects of TPE and TPB on cerebral ischemia-reperfusion injury were demonstrated by enhanced antioxidant enzyme activities, elevated level of the nucleus transportation of nuclear factor erythroid 2-related factor 2 and expressions of antioxidant proteins, with a simultaneous reduction in cell apoptosis and reactive oxygen species level. In conclusion, TPE and TPB exert neuroprotective effects by stimulating the Nrf2 signaling pathway, thereby inhibiting apoptosis.

The hyperpolarization-activated cyclic-nucleotide-gated non-selective cation (HCN) channels play a potential role in the neurological basis underlying drug addiction. However, little is known about the role of HCN channels in methamphetamine (METH) abuse. In the present study, we examined the changes in working memory functions of METH re-exposed mice through Morris water maze test, and investigated the protein expression of HCN1 channels and potential mechanisms underlying the modulation of HCN channels by Western blotting analysis. Mice were injected with METH (1 mg/kg, i.p.) once per day for 6 consecutive days. After 5 days without METH, mice were re-exposed to METH at the same concentration. We found that METH re-exposure caused an enhancement of working memory, and a decrease in the HCN1 channels protein expression in both hippocampus and prefrontal cortex. The phosphorylated extracellular regulated protein kinase 1/2 (p-ERK1/2), an important regulator of HCN channels, was also obviously reduced in hippocampus and prefrontal cortex of mice with METH re-exposure. Meanwhile, acute METH exposure did not affect the working memory function and the protein expressions of HCN1 channels and p-ERK1/2. Overall, our data firstly showed the aberrant protein expression of HCN1 channels in METH re-exposed mice with enhanced working memory, which was probably related to the down-regulation of p-ERK1/2 protein expression.

No abstract

Background: The pathogenesis of diabetes mellitus is mediated mainly by oxidative stress produced by damaged pancreatic β-cells. We identified that an ethyl-acetate fraction (EA) from a cinnamon-cortex extract (CCE) is rich in flavonoid, and showed no toxicity to β cells.Objective: In this study, we evaluated the pharmacologic activities of EA on pancreatic β cells using a model of oxidative stress induced by H2O2 or alloxan.Results: The results showed that EA could significantly reduce reactive oxygen (ROS) accumulation to improve the survival of cells. Western blot showed that EA treatment upregulated expression of nuclear factor erythroid 2 related factor 2, heme oxygenase-1, and gamma glutamylcysteine synthetase. The same model study found that EA also can protect β cells against the apoptosis induced by oxidative stress. Furthermore, EA can enhance insulin secretion in rat and mouse β cell lines treated or not with alloxan or H2O2. The expression of the insulin transcription factor PDX-1 increased in an EA concentration-dependent manner. At last, the major functional compounds of EA analysis showed that three compounds, cinnamyl alcohol, coumarin, and cinnamic acid, had similar effects as EA.Conclusions: In sum, our data suggested that EA fraction from CCE can protect β cells from oxidative stress, and increase insulin secretion to improve the function of β cells. This function might be due to these three compounds found in EA. Our findings provide a theoretical basis and functional molecules for the use of CCE against diabetes mellitus.

Background: Cerebrovascular lesions could induce affective disorders; however, the depression- and anxiety-related symptoms caused by chronic cerebral hypoperfusion (CCH) and the roles of different hyperpolarization-activated cyclic nucleotide-gated (HCN), KCNQ and G protein-coupled inwardly rectifying potassium (GirK) channel subunits in these pathological processes have been poorly elucidated so far. Objective: To investigate the behavioral change and the alteration of HCN, KCNQ, and GirK subunits in amygdale of rats suffered from CCH. Methods: Permanent bilateral occlusion of the common carotid arteries was used to induce CCH. Anxiety and depression levels were assessed by the elevated plus maze test, sucrose preference test and forced swimming test to classify rats as highly anxious or depressive ‘susceptibility’ vs. ‘unsusceptibility’. The expression of brain derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrKB), HCN1/2, KCNQ2/3, and GirK1/2/3 were quantified by Western blotting. Results: The mainly emotional change caused by 4 weeks of CCH is likely to be anxiety-like behavior (50%), accompanied by a down-regulation of BDNF and TrKB expression in amygdale. The increase of HCN1 and decrease of KCNQ3 expression in amygdale may be factors to blame for anxiety-like symptom caused by CCH, and the increase of KCNQ2 and Girk1 expression in amygdale may play a role in resilience to the anxiety induced by CCH. Conclusion: The different subunits of HCN, KCNQ and GirK channels in amygdale may contribute to distinct response to aversive stimuli or stress induced by CCH that evokes divergent influence on anxiety-like behavior in rats.