n-3 polyunsaturated fatty acids improve depression-like behavior by inhibiting hippocampal neuroinflammation in mice via reducing TLR4 expression.

INTRODUCTION: n-3 polyunsaturated fatty acids (PUFAs) are believed to be implicated in the pathogenesis of many inflammation-related diseases, including depression. METHODS: The mouse model of depression was established through chronic unpredictable mild stress (CUMS), the mice were intervened with n-3 PUFAs, and then the expression of toll-like receptor 4 (TLR4) was stimulated with lipopolysaccharides (LPS). Tail suspension test (TST), forced swimming test (FST) and sucrose preference test were performed to monitor the depression behavior of mice. Microglia activation was detected by Iba1 immunofluorescence, and neuronal injury was detected by Nissl staining. Concentrations of tumor necrosis factor (TNF)-α, Interleukin (IL)-6 and IL-1ß in the hippocampus were assessed via enzyme linked immunosorbent assay (ELISA). Quantitative real time polymerase chain reaction was used to detect IL-6, IL-1ß and TNF-α messenger RNA levels. Western blot was utilized for detection of TLR4 protein expression. RESULTS: CUMS significantly reduced the sucrose preference in mice, while increased the immobility time in FST and TST. Moreover, CUMS significantly aggravated microglia activation and neuronal damage in mice and increased the levels of IL-6, IL-1ß and TNF-α in hippocampal tissues, however, intervention with n-3 PUFAs could improve the above effects. Further, the increased TLR4 induced by LPS partially reversed the inhibition of n-3 PUFAs on depression-like behaviors, microglial activation and inflammatory injury of hippocampal neurons. CONCLUSION: n-3 PUFAs may ameliorate depression-like behaviors via reducing hippocampal neuroinflammation in CUMS-induced mice by regulating TLR4 expression, suggesting that n-3 PUFAs may be an effective antidepressant, which provides evidence for future treatment of depression.

Effect of Peony-Glycyrrhiza Decoction on Amisulpride-Induced Hyperprolactinemia in Women with Schizophrenia: A Preliminary Study.

OBJECTIVE: The aim of this study is to observe the effect of Peony-Glycyrrhiza Decoction (PGD) on hyperprolactinemia in women with schizophrenia induced by Amisulpride. MATERIAL AND METHODS: A total of 41 female schizophrenia patients receiving Amisulpride were randomly divided into placebo (n = 20) and PGD groups (n = 21). Maintaining the original Amisulpride dose, the two groups were given placebo and PGD, respectively. The levels of Prolactin (PRL) and other hormones were measured on the initial day and at weeks 4 and 8 after treatment. Changes of clinical symptoms in patients with hyperprolactinemia were observed. The PANSS scores were recorded to assess the psychotic symptoms. RESULTS: Compared with placebo group, level of PRL decreased while Progesterone increased remarkably in the PGD group at weeks 4 and 8 (p < 0.01), and level of Estradiol in the PGD group increased significantly at week 8 (p < 0.05). There were no differences in PANSS scores and biochemical indexes between two groups at weeks 4 and 8. CONCLUSION: PGD can improve symptoms of hyperprolactinemia and hormone levels in women with schizophrenia caused by Amisulpride, without affecting their mental symptoms and biochemical indexes.

Reduction of lipid accumulation in HepG2 cells by luteolin is associated with activation of AMPK and mitigation of oxidative stress.

The present study was carried out to investigate the lipid-lowering effect of luteolin by using a cell model of steatosis induced by palmitate. Incubation of HepG2 cells with palmitate markedly increased lipid accumulation (Oil Red O staining), the genes involved in lipogenesis, including fatty acid synthase (FAS) and its upstream regulator sterol regulatory element binding protein 1c (SREBP-1c), and reactive oxygen species (ROS) production. Luteolin enhanced the phosphorylation of AMP-activated protein kinase α (AMPKα) and its primary downstream targeting enzyme, acetyl-CoA carboxylase (ACC), up-regulated gene expression of carnitine palmitoyl transferase 1 (CPT-1), which is the rate-limiting enzyme in mitochondrial fatty acid ß-oxidation, and down-regulated SREBP-1c and FAS mRNA levels in the absence and presence of palmitate. In addition, luteolin significantly decreased ROS production and ameliorated lipid accumulation in HepG2 cells caused by palmitate. Furthermore, intracellular triglyceride (TG) measurement indicated that the luteolin-mediated reduction of enhanced TG caused by palmitate was blocked by pretreatment with the AMPK inhibitor, compound C. The results suggested that the lipid-lowering effect of luteolin might be partially mediated by the up-regulation of CPT-1 and down-regulation of SREBP-1c and FAS gene expression, possibly by activation of the AMPK signaling pathway, and partially might be through its antioxidative actions.