Loganin alleviates LPS‐activated intestinal epithelial inflammation by regulating TLR4/NF‐κB and JAK/STAT3 signaling pathways

• Published in: The Kaohsiung journal of medical sciences Vol. 36; no. 4; pp. 257 - 264
• Main Authors: Wang, Jia‐Wen, Pan, Yi‐Bin, Cao, Yong‐Qing, Wang, Chen, Jiang, Wei‐Dong, Zhai, Wei‐Feng, Lu, Jin‐Gen
• Format: Journal Article
• Language: English
• Published: BP, Asia Wiley Publishing Asia Pty Ltd 01.04.2020; John Wiley & Sons, Inc; Wiley
• Subjects: Analysis; Caco-2 Cells; Cell Survival - drug effects; Cytokines; Cytokines - metabolism; Drug dosages; Enzyme-linked immunosorbent assay; Gastrointestinal diseases; Humans; Immunoglobulins; Inflammation; Inflammation - chemically induced; Inflammation - metabolism; Inflammation - pathology; Inflammation Mediators - metabolism; Inflammatory bowel disease; Insulin-Like Growth Factor I - pharmacology; Intestinal Mucosa - drug effects; Intestinal Mucosa - pathology; Iridoids - pharmacology; JAK/STAT3 signaling pathway; Janus Kinases - metabolism; Lipopolysaccharides; loganin; Metabolites; NF-kappa B - metabolism; Proteins; Signal Transduction; STAT3 Transcription Factor - metabolism; TLR4/NF‐κB signaling pathway; Toll-Like Receptor 4 - metabolism; Illinois; China; United States > US; California; TLR4/NF-κB signaling pathway; loganin; JAK/STAT3 signaling pathway; inflammation; inflammatory bowel disease
• ISSN: 1607-551X; 2410-8650
• DOI: 10.1002/kjm2.12160

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‐1β, 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.