ABSTRACT
Depression is one of the foremost psychological illness which is closely leagued with inflammation. Crocin is a natural product that exhibits both anti-inflammatory and anti-oxidant activities. However, little is known about anti-inflammatory mechanisms of crocin on LPS-induced anxiety and depressive-like behaviors. The objective of this study is emphasized on neuroprotective role of crocin against LPS-induced anxiety and depressive-like behaviors in mice. It is observed that crocin inhibited LPS-induced production of NO, TNF-α, IL-1ß and ROS in BV-2 microglial cells. Moreover, crocin significantly declined the expression of iNOS, NF-κB p65 and CD16/32 (M1 marker), as well as elevated the expression of CD206 (M2 marker) in BV-2 cell line with decreased LPS-induced anxiety and depressive-like behaviors by improved locomotor activity, reduced sucrose intake, and decreased immobility time in forced swim and tail suspension test in Kunming mice. Expression of NLRP3, ASC and caspase-1 by i.p administration of LPS found to be neutralized with reduction in level of IL-1ß, IL-18 and TNF-α in mouse hippocampus. In conclusion, these results suggested that crocin as a potential therapeutic candidate for neuro-inflammation and depressive-like behaviors induced by LPS. The effect was found to be due to inhibition of NLRP3 inflammasome and NF-κB and its promoted M1 to M2 phenotypic conversion of microglia.
Subject(s)
Anxiety Disorders/drug therapy , Carotenoids/pharmacology , Depressive Disorder/drug therapy , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Psychotropic Drugs/pharmacology , Animals , Animals, Outbred Strains , Anxiety Disorders/immunology , Cell Line , Depressive Disorder/immunology , Inflammasomes/drug effects , Inflammasomes/metabolism , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/psychology , Lipopolysaccharides , Mice , Microglia/drug effects , Microglia/immunology , Neuroprotective Agents/pharmacology , Signal Transduction/drug effectsABSTRACT
Chondrocyte dysfunction has been demonstrated to be a major inducer of osteoarthritis(OA). The pathological mechanism of chondrocyte dysfunction is definitely multifactoral, but oxidative stressis regarded as one of the leading causes of apoptosis, autophagy, senescence, and mitochondrial dysfunctionin chondrocytes. Strategies for arresting oxidative stress- induced chondrocyte dysfunction have been considered as potential therapeutic targets for OA. Recently, fork head box O (FoxO) transcription factors have been determined to play a protective role in chondrocytes through the regulation of autophagy and defense against oxidative stress; they also regulate growth, maturation, and matrix synthesis. To explore FoxO' s potential role in the treatment of OA, we first discussed the recent advances in the field of oxidative stress- induced chondrocyte dysfunction and then emphasized the protective role of fox otranscription factors as a potential molecular target for the treatment of OA. Understanding the function of fox otranscription factors will be important in designing next- generation therapies to prevent or reverse the development of OA.
ABSTRACT
OBJECTIVE: To observe the protective effect of rutin (RUT) on neuronal cells against sodium nitroprusside (SNP) induced neurotoxicity. METHODS: PC12 cells were treated with different concentration of SNP for 24 h and MTT assay was applied to analyze the survival rate; PC12 cells were pretreated with rutin for 1 h, and then incubated for 24 h with SNP. MTT assay, morphological observation, as well as immunofluorescence were performed to evaluate both the SNP neurotoxicity and the protective effects of RUT, Western blot was used to analyzed the level of phosphorylated extra cellular regulated protein kinases (ERK1/2) after treatment with RUT, the results were also testified in primary cultured neurons. RESULTS: Results from MTT assay showed that SNP caused cell death in a concentration-dependent manner in PC12 cells. The effect of SNP was observed at 200 - 1 000 micromol/L and was significant at 800 micromol/L. 25 micromol/L rutin partly blocked the neurotoxicity of SNP by preventing PC12 cells from apoptosis. Hoechst and PI staining indicated that SNP treatment decreased the number of viable cells and induced shrinkage and aggregation of the nucleus, whereas RUT pretreatment attenuated the toxic effects of SNP, after treatment with RUT in PC12 cells, the phosphorylation of ERK1/2 was increased and peaked at 20 min. Most importantly, the protective effect of RUT on PC12 cells was confirmed on cultured neurons. CONCLUSION: RUT possesses protective effect against neuronal apoptosis induced by SNP and this effect may be partially related with ERK1/2 signaling.
