Thymol promotes cell proliferation and protects against LPS-induced intestinal inflammation via activation of the EGFR/PI3K pathway.

Sepsis-induced intestinal inflammation affects the rapid turnover of intestinal epithelial cells, disrupting the intestinal barrier. Thymol (THY), as a plant-derived active component, is involved in protecting the intestinal barrier, but the specific mechanisms are still unclear. In this research, thymol increases the amount of cells and enhances the proliferative activity, notably in the G2/M phase of IPEC-J2 cells. Molecular docking indicated that pocket-like binding of thymol with epidermal growth factor receptor (EGFR) protein. Inhibition of EGFR expression diminished the cell proliferation viability after thymol treatment. In vivo, thymol prevented LPS-induced reduction in jejunal villi length, impairment of MUC2 and TFF3, decreased levels of Reg 3β and Reg 3γ, and elevated the pro-inflammatory cytokines. Moreover, thymol inhibited the EGFR-PI3K/AKT and NF-κB pathways and mitigated intestinal cell inflammation and apoptosis. Collectively, thymol inhibited apoptosis by regulating intestinal barrier and activating the EGFR-PI3K/AKT signaling pathway, providing evidence for alleviating intestinal inflammation under sepsis. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-025-01833-y.