Mangiferin exerts neuroprotective effects against focal cerebral ischemia in mice by regulating NF-κB signaling pathway.

PURPOSE: Mangiferin is a natural free radical scavenging antioxidant that induces excitation of the central nervous system. However, the mechanism of neuroprotective effect of mangiferin on focal cerebral ischemia has not been fully investigated. The aim of this study was to investigate the protective effect of mangiferin on focal cerebral ischemia in mice. METHODS: Middle cerebral artery occlusion (MCAO) was performed to investigate the effect of mangiferin on focal cerebral ischemia. Mice were randomly divided into 5 groups: sham, MCAO, MCAO + 5 mg/kg mangiferin, MCAO + 20 mg/kg mangiferin and MCAO + 5 mg/kg nimodipine. Neurobehavioral scores, brain edema, brain injury scores, relative infarct size and expression of some inflammatory factors in the brain were evaluated. NF-κB pathway was detected by Western blotting and immunofluorescence. RESULTS: The results showed that mangiferin effectively attenuated MCAO-induced brain injury, including improvement of neurological impairment, reduction of brain edema, and reduction of infarct size. Compared with the MCAO group, mangiferin significantly inhibited MCAO-induced neuroinflammation, which can be proved by reduced expression levels of TNF-α, IL-1ß, iNOS and COX-2. In addition, we found that phosphorylation of IκBα was inhibited and the expression of NF-κB p65 in the nucleus was reduced after the addition of mangiferin. CONCLUSION: Our study suggested that mangiferin exerts neuroprotective effects on focal cerebral ischemia in mice by regulating the NF-κB signaling pathway. Mangiferin may be an effective treatment for cerebral ischemia and other neurological disorders.

Resveratrol inhibited hepatocyte apoptosis and alleviated liver fibrosis through miR-190a-5p /HGF axis.

BACKGROUND: Hepatocyte apoptosis plays an important role in the progression of liver fibrosis. Overexpression of HGF (Hepatocyte growth factor) can reduce hepatocyte apoptosis and alleviate liver fibrosis. Our study aims to investigate whether resveratrol (Res) can alleviate liver fibrosis through miR-190a-5p /HGF axis. METHODS: The TGF-ß1 (transforming growth factor-ß1)-induced primary hepatocyte model in vitro and CCl4-induced liver fibrosis model in vivo were established. Hepatocyte apoptosis was determined by flow cytometry and TdT-mediated dUTP nick-end labeling (TUNEL) assay. HE (hematoxylin and eosin) staining and Sirius red staining were performed to observe the pathological changes of the liver tissues. Western blotting was used to determine the expression of apoptosis-associated proteins and HGF. Quantitative Real-time PCR (QRT-PCR) was used to quantify miR-190a-5p expression. The dual-luciferase reporter assay was performed to verify the targeting relationship between miR-190a-5p and HGF. RESULTS: Hepatocyte apoptosis and miR-190a-5p expression level were increased in TGF-ß1-induced cell models in vitro while the results were reversed after treatment with Res. Besides, miR-190a-5p negatively regulated HGF expression, and miR-190a-5p regulated hepatocyte apoptosis by targeting HGF. Res reduced the apoptosis of hepatocytes and the effect was achieved by decreasing the expression levels of miR-190a-5p and increasing HGF expression in vitro. Moreover, experiments in vivo verified that Res reduced apoptosis of the hepatocytes reduced AST, and ALT levels, as well as raised Albumin levels in the serum. Apart from that, Res decreased the expression ofmiR-190a-5p and increased HGF levels at the same time, and further reduced liver fibrosis. CONCLUSION: In summary, our study indicated that Res could inhibit the up-regulation of miR-190a-5p caused by CCl4 or TGF-ß1. And then the decreased miR-190a-5p could further lessen the hepatocyte apoptosis by increasing HGF levels and finally relieving liver fibrosis.

Astrocytes-induced neuronal inhibition contributes to depressive-like behaviors during chronic stress.

Although emerging evidence has highlighted the heterogeneities of astrocytes under physiological versus pathological conditions, little is known regarding these processes in different brain regions during stress. Thus, the present study established a mouse model of chronic social defeat stress (CSDS) and isolated astrocytes from the medial prefrontal cortex (mPFC) and hippocampus. The results revealed dramatic A1-specific (neurotoxic phenotype) astrocytic responses, depressive-like behaviors, and significant inhibition of neuronal activities in both the mPFC and hippocampus according to electrophysiological data. Subsequently, astrocytes in the mPFC and hippocampus of CSDS mice were suppressed and this reversed the astrocytic responses and rescued depressive-like behaviors. Furthermore, when astrocytes were activated in the mPFC and hippocampus in healthy mice, there was a non-specific phenotypic activation of astrocytes in the absence of depressive-like behaviors. Next, microglia were depleted and the mice subsequently performed in the CSDS model; this reduced astrocyte responses and restored depressive-like behaviors. On the other hand, when microglia were depleted but astrocytes were activated in CSDS mice, this abolished the restoration of microglia depletion-induced depressive-like behaviors. Taken together, these results indicate that neuronal inhibition by astrocytes in the mPFC and hippocampus contributed to depressive-like behaviors mediated by activated microglia. This study provides evidence regarding the interaction of microglia and astrocytes during stress and how that relationship can trigger depressive-like behaviors.

Social housing promotes cognitive function through enhancing synaptic plasticity in APP/PS1 mice.

Previous studies have shown that loneliness increases the risk of AD (Alzheimer's disease) onset, while active and frequent social housing delays the onset of cognitive impairment. The mechanism of how this occurs remains unclear. In this study, we investigated how social interaction affected cognitive function and AD pathology in APP/PS1 (amyloid precursor protein/presenilin-1) mice. APP/PS1 mice were divided into either a social isolation (SI) group, a social contact with one mouse (SCO) group, or a social contact with five mice (SCF) group. Our results demonstrated that social housing improved the behavioral performance of APP/PS1 mice in Morris Water Maze testing, without significantly altering the rates of amyloid plaque deposition or amyloidogenic APP processes. Furthermore, the synaptic function, dendritic spine density, and complexity of neuronal network were notably increased in the SCF group, as compared to the SI and SCO groups. Additional protein and mRNA analyses of isolated astrocyte and microglia revealed that several glial genes related to regulation and anti-inflammatory progression were significantly upregulated, while pro-inflammatory markers were decreased. These findings highlight the important role of quality social communication (five mice not one mice) on maintaining neuronal function during AD pathogenesis and provide evidence to place great emphasis of family care of AD patients.

[Effects of phosphocreatine on plasma brain natriuretic peptide level in elderly patients with chronic congestive heart failure].

OBJECTIVE: To investigate the therapeutic effects of phosphocreatine in elderly patients with chronic congestive heart failure (CHF) and its effects on plasma brain natriuretic peptide (BNP). METHODS: Forty elderly patients with chronic CHF were randomly divided into two groups to receive basic treatment (control group) and additional phosphocreatine treatment (treatment group) with a treatment course of 8 weeks. The patients were evaluated for improvement in New York Heart Association (NYHA) functional class, symptoms, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and left ventricular ejection fraction (LVEF) and the levels of BNP before and after treatment. RESULTS: After 8 weeks of treatment, the overall efficacy rate was significantly higher in treatment group than in the control group, and LVESD, LVEDD, LVEF and BNP level of the treatment group were significantly lowered in comparison with those of the control group (P<0.05). CONCLUSION: Phosphocreatine in addition to the basic treatment can reduce the BNP level and improve the cardiac systolic and diastolic function in elderly patients with chronic CHF.