Anti-depression-like effect of Mogroside V is related to the inhibition of inflammatory and oxidative stress pathways.

Siraitia grosvenorii (SG) is an edible medicinal plant found mainly in Guangxi, China, and Mogroside V (MGV) is the main component of SG extract. Previous research has shown that SG and MGV exert anti-inflammatory, antioxidative and neuroprotective effects. However, it is not clear whether MGV has anti-depression-like effect. In this study, we evaluated the neuroprotective effects and anti-depression-like effect of MGV both in vitro and in vivo. By performing in vitro tests, we evaluated the protective effects of MGV on PC12 cells with corticosterone-induced injury. In vivo tests, we used the chronic unpredictable mild stress (CUMS) depression model. Fluoxetine (10 mg/kg/day) and MGV (10 or 30 mg/kg/day) were administered by gavage for 21 days, and the open field test (OFT), novelty suppressed feeding test (NSFT), Tail suspension test (TST), and forced Swimming test (FST) were used to evaluate the depressive-like behaviors. In addition, we investigated the role of proinflammatory cytokines (IL-1ß, IL-6, and TNF-α) and anti-inflammatory cytokine (IL-4) in the hippocampal and cortex tissues. The levels of Superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-PX) in hippocampal and cortex tissues were also measured. Pathological changes in the hippocampal dentate gyrus and cortex regions were detected by immunofluorescence and Western blotting was used to measure the protein expression of BDNF, TrkB, TNF-α, and AKT. The results showed that MGV had a protective effect on PC12 cells with corticosterone-induced incurred injury. In addition, MGV treatment relieved the depressive symptoms and significantly reduced inflammatory levels (IL-1ß, IL-6, and TNF-α). MGV also significantly reduced oxidative stress damage and reduced the levels of apoptosis in hippocampal nerve cells. These results suggested that the anti-depressive effect of MGV may occur through the inhibition of inflammatory and oxidative stress pathways and the BDNF/TrkB/AKT pathway. These findings provide a new concept for the identification of new anti-depressive strategies.

The role of MARCH9 in colorectal cancer progression.

Colorectal cancer (CRC) is the third most common cancer with a high global incidence and mortality. Mutated genes or dysregulated pathways responsible for CRC progression have been identified and employed as biomarkers for diagnosis and prognosis. In this study, a ubiquitination regulator, MARCH9, was shown to accelerate CRC progression both in vitro and in vivo. CRC samples from The Cancer Genome Atlas (TCGA) showed significantly upregulated MARCH9 expression by individual cancer stage, histological subtype, and nodal metastasis status. Knockdown of MARCH9 inhibited, while MARCH9 overexpression promoted, CRC cell proliferation and migration. Knockdown of MARCH9 also induced CRC cell apoptosis and caused cell cycle arrest. Further investigation showed that MARCH9 promoted CRC progression by downregulating the expression of a deubiquitinase cylindromatosis (CYLD) gene and activating p65, a member of the nuclear factor-κB (NF-κB) protein family. Finally, in vivo xenograft studies confirmed that MARCH9 knockdown suppressed tumor growth in nude mice. Thus, this study demonstrated that MARCH9 may be a novel and effective therapeutic target for CRC therapy.

Muscone with Attenuation of Neuroinflammation and Oxidative Stress Exerts Antidepressant-Like Effect in Mouse Model of Chronic Restraint Stress.

Major depressive disorder (MDD) is a common mental disorder with high morbidity. Stress negatively affects for MDD development, whereby transport of stress-induced inflammatory mediators to the central nervous system (CNS) is associated with the etiology of mood disorders. Muscone is a pharmacologically active ingredient isolated from musk, with anti-inflammatory and neuroprotective effects. We hypothesized that muscone may ameliorate depression-like behavior by regulating inflammatory responses. To test this hypothesis, we used the chronic restraint stress (CRS) depression model, and CRS mice were treated with muscone (10 mg/kg, i.g., respectively) for 14 days. The effects of the drug on depressive-like behaviors were evaluated via the open field test (OFT), novelty-suppressed feeding test (NSFT), tail suspension test (TST), and forced swimming test (FST). Quantitative reverse transcription-PCR (qRT-PCR) was utilized to assess levels of proinflammatory cytokines (IL-6, TNF-α, COX2, and IL-1) and the anti-inflammatory cytokines (IL-4 and IL-10). We also determined levels of oxidative stress factors (malondialdehyde, superoxide dismutase, and glutathione peroxidase), as well as doublecortin (DCX) expression by immunofluorescence. The results showed that depression-like behavior and inflammatory levels were improved after muscone treatment. Muscone also significantly improved neurogenesis in the CRS mouse hippocampus and decreased oxidative stress in both the central and peripheral nervous systems. In conclusion, this work is the first to demonstrate that muscone has an antidepressant effect using a CRS model. Oxidative stress, neurogenesis, and inflammatory pathways are key factors affected by the drug and may represent new therapeutic targets to treat MDD, in this impact. These results may represent a new therapeutic target for MDD.