Linderanine C regulates macrophage polarization by inhibiting the MAPK signaling pathway against ulcerative colitis.

Ulcerative colitis (UC) is a chronic non-specific inflammatory disease involving the mucosa and submucosa of the rectum and colon. Lindera aggregate (Sims) Kosterm is a traditional Chinese herb used for thousands of years in the treatment of gastrointestinal diseases. Previously, we have demonstrated that the extracts of Lindera aggregate have good anti-UC effects, but their pharmacodynamic active components have not been fully clarified. Therefore, we explored the therapeutic effect of Linderanine C (LDC), a characteristic component of Lindera aggregata, on UC and its mechanism in this study. Firstly, we found that LDC could significantly reduce the disease activity index of UC and improve shortened colon and pathological changes in vivo. Colon tissue transcriptomics suggested that the anti-UC effect of LDC might be related to its anti-inflammatory activity. Cellular experiments revealed that LDC could inhibit the expression of the M1 cell marker CD86 in RAW264.7 cells, reduce the production of inflammatory mediators such as IL-6 and TNF-α, and have good anti-inflammatory activity in vitro. Cellular transcriptomics reveal the potential involvement of the MAPK signaling pathway in the anti-inflammatory effect of LDC. The co-culture assay confirmed that LDC could significantly reduce inflammation-mediated intestinal epithelial cell injury. In conclusion, LDC was able to inhibit macrophage M1 polarization and reduce inflammatory mediator production by inhibiting the MAPK signaling pathway, effectively improving UC.