Quercetin attenuates brain apoptosis in mice with chronic unpredictable mild stress-induced depression.

BACKGROUND: Depression is a common psychiatric disorder with limited effective treatments. Research suggests that depression involves apoptosis mechanisms. Quercetin (QUE) has been reported to have anti-apoptotic activities. In this study, we aimed to investigate the effects and mechanisms of QUE in chronic unpredictable mild stress (CUMS)-induced depression. METHODS: After establishing mouse models of CUMS-induced depression, the mice were randomly assigned into four groups: control, CUMS, CUMS+QUE, and CUMS+Fluoxetine (FLX). The body weight of the mice was measured during the study. Then, depression-associated behaviors were evaluated using the sucrose preference test (SPT), novelty suppressed feeding test (NSFT), forced swim test (FST) and tail suspension test (TST). Apoptosis in the hippocampus and prefrontal cortex was determined using flow cytometry. Bcl-2 and Nrf2 protein expressions in the hippocampus and prefrontal cortex were also detected. Furthermore, Western blot was used to measure the protein levels of p-ERK, ERK, p-CREB, CREB, and Nrf2 in brain tissues. RESULTS: QUE or FLX administration increased the body weight of the CUMS mice. Behavioral tests indicated that CUMS mice developed a state of depression, but QUE or FLX treatment improved their depression-associated behaviors. Meanwhile, QUE or FLX treatment decreased apoptosis in the hippocampus and prefrontal cortex. Furthermore, the decreased Nrf2 protein expression, ERK and CREB phosphorylation in CUMS group were enhanced by QUE or FLX administration. CONCLUSION: QUE could attenuate brain apoptosis in mice with CUMS-induced depression, and the mechanism may be related to the ERK/Nrf2 pathway, indicating that QUE could be a potential treatment for depression.

Quercetin mitigates depression-like behavior via the suppression of neuroinflammation and oxidative damage in corticosterone-induced mice.

Depression is a clinically common and easily overlooked mental disease. Quercetin is a flavonoid compound, which has anti-inflammatory and antioxidant roles. Previous reports presented the anti-depressant role of quercetin. Nevertheless, the latent mechanism of the anti-depressant function of quercetin is blurry. This research aimed to probe its effects on corticosterone (CORT)-induced depression-like behaviors and explore the underlying mechanism. A depression model was established by subcutaneous injection of CORT (20 mg/kg). Thereafter, CORT-treated mice were given 40 mg/kg and 80 mg/kg of quercetin by gavage. This study found that quercetin mitigated depression-like behaviors, as evidenced by increased the number of line crossings, swimming time, and time spent in open arm and reduced thigmotaxis time in CORT-challenged mice in open field test and decreased immobility time as well as the swimming and climbing time in forced swim test and increased number of head dips, time spent and entries in open arm elevated plus maze test. Also, quercetin exerted anti-inflammatory and anti-oxidation effects in hippocampus and prefrontal cortex of CORT-induced mice. Additionally, quercetin alleviated the pathological injury of the liver tissue and weakened alkaline phosphatase (ALP) and alanine aminotransferase (ALT) concentrations of the serum in CORT-induced mice. Quercetin also suppressed Caspase-3 content but advanced vascular endothelial growth factor (VEGF) and brain derived neurotrophic factor (BDNF) contents in hippocampus of CORT-treated mice. Based on these results, quercetin mitigated CORT-induced depression-like behaviors, and the mechanism was partly related to the repression of neuroinflammation and oxidative damage.

Ginkgo leaf extract and dipyridamole injection as adjuvant treatment for acute cerebral infarction: Protocol for systemic review and meta-analysis of randomized controlled trials.

BACKGROUND: Acute cerebral infarction (ACI) is one of the most commonly seen cerebral vascular disease and the current therapy options are not satisfied. Ginkgo leaf extract and dipyridamole injection (GDI) is widely used as adjuvant therapy for ACI. However, there is no systemic review and meta-analysis published regarding the efficacy and safety of GDI. Herein, we describe the protocol of a proposed study aims to systemically evaluate the efficacy and safety of GDI in ACI patients. METHODS: Five electronic databases (Medline, EMBase, Cochrane database, China National Knowledge Infrastructure, and Wanfang database) will be searched up to February 28, 2018. Randomized controlled trials (RCTs) meet the eligibility criteria will be identified and included. Data synthesis will be run using RevMan software after the data extraction and risk of bias assessment of included studies. The primary outcomes of this study are effective rate and adverse event rate. RESULTS: This study will provide a high-quality synthesis of RCTs on the efficacy and safety of GDI as an adjuvant therapy in the treatment of ACI. CONCLUSION: This systemic review and meta-analysis will provide high quality evidence to evaluate GDI as adjuvant therapy in patients with ACI.Registration: PEROSPERO CRD42018107112.

Clinical outcomes of prolonged infusion (extended infusion or continuous infusion) versus intermittent bolus of meropenem in severe infection: A meta-analysis.

BACKGROUND: Meropenem exhibits time-dependent antimicrobial activity and prolonged infusion (PI) (extended infusion or continuous infusion, EI or CI) of meropenem can better achieve pharmacodynamics target when comparing with intermittent bolus (IB). However, the clinical outcomes between two groups remain inconclusive. OBJECTIVE: To evaluate current published literatures by meta-analysis to ascertain whether PI of meropenem can improve clinical outcomes. METHODS: Medline, Cochrane database and EMBASE were searched. Randomized control trails (RCT) and observational studies which compared the clinical outcomes of PI and IB groups were included and evaluated for quality. The data of studies were extracted and meta-analysis was performed using Revman 5.3 software. RESULTS: Six RCTs and 4 observation studies with relatively high quality were included in this analysis. Compared to IB group, PI group had a higher clinical success rate (odd ratio 2.10, 95% confidence interval 1.31-3.38) and a lower mortality (risk ratio 0.66, 95% confidence interval 0.50-0.88). The sensitivity analysis showed the results were stable. CONCLUSION: PI of meropenem was associated with a higher clinical improvement rate and a lower mortality. It is recommended for patients with severe infection or infected by less sensitive microbial.