The protective effect of teprenone in TNBS-induced ulcerative colitis rats by modulating the gut microbiota and reducing inflammatory response

Abstract

Objective

Ulcerative colitis (UC), a chronic and refractory nonspecific inflammatory bowel disease, affects millions of patients worldwide and increases the risk of colorectal cancer. Teprenone is an acylic polyisoprenoid that exerts anti-inflammatory properties in rat models of peptic ulcer disease. This in vitro and in vivo study was designed to investigate the effects of teprenone on UC and to explore the underlying mechanisms.

Methods

Human intestinal epithelial cells (Caco-2 cells) serve as the in vitro experimental model. Lipopolysaccharide (LPS, 1 μg/mL) was employed to stimulate the production of pro-inflammatory cytokines (interleukin [IL]-6, IL-1β, and tumor necrosis factor [TNF]-α), Toll-like receptor-4 (TLR4), MyD88 expression, and NF-κB activation. A trinitrobenzene sulfonic acid (TNBS)-induced chronic UC rat model was employed for the in vivo assay.

Results

Pro-inflammatory cytokine stimulation by LPS in Caco-2 cells was inhibited by teprenone at 40 μg/mL through the TLR4/NF-κB signaling pathway. Teprenone attenuated TNBS-induced UC, decreased myeloperoxidase and malondialdehyde, induced TLR4 expression and NF-κB activation, and increased glutathione and zonula occludens-1 level in the rat colonic tissue. Moreover, Fusobacterium, Escherichia coli, Porphyromonas gingivalis elevation, and Mogibacterium timidum decline in UC rats were inhibited by teprenone.

Conclusion

Based on our results, the protective effects of teprenone for UC may be related to its ability to modulate the gut microbiota and reduce the inflammatory response.

Keywords:

• Gut microbiota
• inflammation
• teprenone
• TLR4/NF-κB signaling pathway
• ulcerative colitis

Authors’ contributions

WZ and YY designed the research and supervised the study. JY and TS performed the experiments and wrote the manuscript. SZ, JM, QZ, and KL performed data analysis. All authors read and approved the final version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This study is funded by the National Key R&D Program of China (Grant/Award Number: 2018YFC2000301) granted to Songbai Zheng.