The therapeutic mechanism of borneol acetate in alleviating ulcerative colitis by regulating the intestinal flora

Abstract

Ulcerative colitis (UC) is a chronic and relapsing inflammatory bowel disease with an increasing global burden. Although various terpenoids have demonstrated significant efficacy against UC, the therapeutic mechanism of bornyl acetate (BA), a monocyclic diterpene derived from pine needle essential oil (PNEO), remains unclear. This study systematically investigated the anti-inflammatory effects and microbiota-modulating mechanisms of PNEO and BA by using an integrated approach that combined in vitro and in vivo models with 16S rRNA sequencing. These results showed that while PNEO significantly inhibited pro-inflammatory mediators like NO and TNF-α, its therapeutic efficacy against UC was modest. In contrast, BA exerted potent anti-inflammatory effects by downregulating the transcriptional activity of p65 in the NF-κB pathway. Furthermore, BA enhanced the transcription and expression of tight junction proteins (ZO-1, claudin-1, and occludin), thereby restoring intestinal barrier integrity in mice with UC. Moreover, BA treatment effectively suppressed the abnormal expansion of opportunistic pathogens (Erysipelotrichaceae, Saccharimonadaceae, Escherichia-Shigella, Turicibacter, Ruminococcus and Candidatus Saccharimonas) while significantly promoting the proliferation of the potential probiotic Akkermansia. Spearman correlation analysis revealed that the abundance of Akkermansia was negatively correlated with p65 transcriptional activity in the NF-κB pathway but positively correlated with anti-inflammatory cytokine IL-10 and the mRNA levels of barrier proteins (ZO-1 and occludin). In conclusion, these findings indicated that BA alleviates UC through a synergistic mechanism encompassing NF-κB pathway inhibition, microbiota homeostasis restoration and intestinal barrier repair. This discovery offers a theoretical basis for novel functional foods leveraging terpenoids to restore gut microecological balance.