ABSTRACT
Inflammatory bowel disease (IBD) is a chronic, recurrent gastrointestinal inflammation that affects millions of people around the world. Loganin, an iridoid glycoside, has shown the anti-inflammatory effects. However, the effect of loganin on IBD and its underlying molecular mechanism are not clear. The present study aimed to investigate whether loganin could alleviate IBD and its mechanisms. The intestinal epithelial Caco-2 cell line was treated with lipopolysaccharide (LPS) to establish an in vitro IBD model. MTT assay was used to detect cell viability. The expression and release level of inflammatory factors were determined by both real-time-PCR and ELISA. Western blotting was used to assess the NF-κB and JAK/STAT3 pathway-related protein levels. The results showed that loganin repressed the expression and release of IL-6, TNF-α, and IL-1ß, and inhibited TLR4/NF-κB and JAK/STAT3 signaling pathways in a concentration-dependent manner. Overexpression of TLR4 could reverse the effect of loganin, leading to activation of NF-κB signaling and production of inflammatory factors. Meanwhile, IGF-1, a JAK/STAT3 signaling activator, could also reverse the anti-inflammation effect of loganin. In conclusion, loganin inhibited LPS-activated intestinal epithelial inflammation by repressing TLR4/NF-κB and JAK/STAT3 signaling pathway.
Subject(s)
Inflammation/metabolism , Inflammation/pathology , Intestinal Mucosa/pathology , Iridoids/pharmacology , Janus Kinases/metabolism , NF-kappa B/metabolism , STAT3 Transcription Factor/metabolism , Toll-Like Receptor 4/metabolism , Caco-2 Cells , Cell Survival/drug effects , Cytokines/metabolism , Humans , Inflammation/chemically induced , Inflammation Mediators/metabolism , Insulin-Like Growth Factor I/pharmacology , Intestinal Mucosa/drug effects , Lipopolysaccharides , Signal TransductionABSTRACT
OBJECTIVE: To evaluate the pre-clinical effect of YJ-XCC1Z3 on the treatment of depression with the mice mouse. METHOD: YJ-XCC1Z3 was administered at the dose of 405 mg x kg(-1) and 135 mg x kg(-1) to observe the locomotor activity with the mouse locomotor activity recorder apparatus, to observe the effect of YJ-XCC1Z3 on the duration of immohility in the mouse forced swimming test and tail suspension test, to observe the effect of YJ-XCC1Z3 on the body temperature and the metabolism of monoamine neurotransmitters in mouse brain in the mouse model of reserpine induced hypothermia, and to observe the effect of YJ-XCC1 Z3 on the times of 5-HTP induced head-twitches in mice. RESULT: There were no significant changes in the locomotor activity, but a significant reduction in the immobility time was observed in the mice treated with YJ-XCC1Z3 405 mg x kg(-1) and imipramine in the forced swimming test and the tail suspension test. YJ-XCC1Z3 135 mg x kg(-1) and 405 mg x kg(-1) could improve the range of reserpine induced hypothermia in mice, and the latter could also enhance the times of 5-HTP induced head-twitches in mice. YJ-XCC1Z3 405 mg x kg(-1) and 135 mg x kg(-1) could increase the content of 5-HT and NE and decrease the ratio of 5-HIAA/5-HT in mouse brain, but the dose of 405 mg x kg(-1) could decrease the content of DA. The dose of 405 mg x kg(-1) could increase the content of 5-HIAA and had no obvious effect on the content of HVA and DOPAC. CONCLUSION: YJ-XCC1Z3 shows potent antidepressant effect by improving the behaviour of the mouse in depression and not inducing hyperlocomotion in the mice. This effect results in the increase of the content of 5-HT and NE in the mouse brain. YJ-XCC1Z3 can decrease the metabolism of 5-HT to effect the content of 5-HT.
