Objective To investigate the effects of proanthocyanidins on depressant-like behaviors and the structure of adrenal gland in chronic unpredictable mild stress (CUMS) rats. Methods Rats were randomly divided into 6 groups:control group, stressed group (CUMS + vehicle), three treatment groups (CUMS + proanthocyanidins 25,50,100 mg·kg-1,respectively) ,and imipramine group (CUMS + imipramine 10 mg·kg-1). Used the CUMS model in rats to investigate the effects of chronic oral administration (21 days) of proanthocyanidins and imipramine (ip) on the open-field;and forced swimming and sucrose consumption tests and the ratio of adrenal gland/body weight,and its thickness were examined by HE stain. Results Compared with control group, rats subjected to CUMS exhibited increased ratio of adrenal gland /body weight ( P < 0. 01), less sucrose consumption( P<0.01) and inhibited in the open-field test( P<0.01) as well as more despair time in the forced swimming test( P<0.01). While compared with stressed group,treatments with proanthocyanidins (25,50,100 mg·kg-1, po ,21 days) could significantly improve the activities in open-field test ((39.6±3.4) vs (49±4.5), (52.6±3.7),(54.1±1.8) ;all P<0.01) and sucrose consumption( (5.8±2.5)ml vs (8.1±3.3)ml,(8.5±4.1) ml, (9.2±2.6) ml; P < 0.05, P < 0.05, P < 0.01 respectively); Meanwhile, it could reduce the duration time in forced swimming test significantly( (103.5±10.2)s vs (83.7±8.8)s,(75.8±5.9)s,(67.2±6.5)s; all P<0.01) as well as thickness of the adrenal gland(P<0.05, P<0.01).Conclusions This study suggests that the proanthocyanidins (25,50,100 mg·kg-1) has an antidepressant-like effects in CUMS rats. The antidepressant actions of proanthocyanidins, in some degrees, may be related with the regulation of the adrenal gland's structure.

Objective:To investigate the effect and mechanism of 6-formylindolo[3,2-b]carbazole (FICZ) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Methods:Male C57BL/6J mice aged 8-12 weeks were divided into 4 groups with 8 mice in each group, according to the method of simple random sampling. Sepsis-induced ALI mice model was established by intraperitoneal injection of LPS 5 mg/kg (LPS group), and phosphate buffer saline (PBS) control group (PBS group) was injected with equal volume of PBS. The LPS+FICZ group was intervened by intraperitoneal injection of 1 μg FICZ 1 hour after LPS stimuli, while the FICZ control group (FICZ group) was given the same amount of FICZ 1 hour after intraperitoneal injection of PBS. Serum and lung tissue were collected 24 hours after LPS stimuli, and the pathological changes of lung tissue were analyzed by hematoxylin-eosin (HE) staining and wet/dry weight (W/D) ratio of lung tissue. The concentrations of inflammatory factors in serum and lung tissue were detected by enzyme linked immunosorbent assay (ELISA). The expression levels of endoplasmic reticulum stress signaling pathway related molecules were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:Compared with PBS group, inflammatory cell infiltration, alveolar collapse and obvious alveolar exudative lesions had increased, lung tissue W/D ratio was significantly increased, serum interleukin-6 (IL-6) level, lung tissue IL-6 mRNA expression, and the mRNA expressions of glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), CCAAT/EBP homologous protein (CHOP), and the protein expressions of GRP78, PERK, activating transcription factor 6 (ATF6), CHOP in lung tissue were significantly increased in LPS group. However, the indexes of FICZ group were not affected. Compared with LPS group, LPS+FICZ group had less inflammatory cell infiltration, relatively intact alveolar structure. Lung W/D weight ratio in LPS+FICZ group was significantly decreased (5.38±0.10 vs. 6.60±0.30, P < 0.01), so as serum IL-6 (ng/L: 15.55±3.77 vs. 32.22±3.84) and lung IL-6 mRNA expression (2 -ΔΔCt: 0.79±0.21 vs. 6.89±0.92, both P < 0.01). The mRNA expressions of GRP78, PERK and CHOP were also significantly decreased [GRP78 mRNA (2 -ΔΔCt): 1.90±0.16 vs. 7.55±1.29, PERK mRNA (2 -ΔΔCt): 1.68±0.20 vs. 4.54±0.89, CHOP mRNA (2 -ΔΔCt): 1.13±0.24 vs. 4.44±1.13, all P < 0.05], and the protein expressions of GRP78, PERK, ATF6 and CHOP were significantly decreased (GRP78/GAPDH: 0.59±0.02 vs. 0.77±0.01, PERK/GAPDH: 0.48±0.03 vs. 1.04±0.05, ATF6/GAPDH: 0.51±0.03 vs. 0.65±0.01, CHOP/GAPDH: 0.91±0.05 vs. 1.11±0.07, all P < 0.05). Conclusion:FICZ protects LPS-induced ALI possibly via suppressing endoplasmic reticulum stress and reducing IL-6 expression in blood and lung tissue.

Immunosuppression plays a critical role in death of sepsis. Innate immunity is the first line defense to prevent pathogen invasion, and neutrophils, macrophages, dendritic cells and natural killer cells (NK cells) are closely involved in the process of the immune-regulation during sepsis. Recently, metabolic reprogramming in immune cells is known as a keystone for immune intervention therapy in sepsis. Here, we focus on the recent advances in metabolic regulation in neutrophils, macrophages, dendritic cells and NK cells including glycolysis, fatty acid synthesis, fatty acid oxidation and arginine metabolism involved in the immune-regulation of sepsis. This review will be helpful to summarize the mechanisms underlying sepsis-induced immunosuppression.