Background Piper nigrum essential oil (PnEO) possesses pleasant aroma, unique flavor, and various bioactivities; however, its role against colitis remains unclear. Purpose In this study, we investigated the role of PnEO in relieving colitis and explored its potential mechanisms in a mouse model of dextran sulfate sodium (DSS)–induced colitis. Methods Initially, we identified and quantified the components of PnEO by gas chromatography-mass spectrometry (GC–MS). Subsequently, we investigated the protective role of PnEO (50 and 200?mg/kg) in DSS-induced colitis in mice by evaluating disease activity index (DAI) scores and colon length, and performing histological analyses. Eyeball blood was collected and cytokines were determined using ELISA kits. The anti-inflammatory mechanisms of PnEO were analyzed by western blot (WB) and immunohistochemistry (IHC). The intestinal barrier function was evaluated according to tight junction (TJ) protein mRNA levels. We used 16S rRNA gene sequencing to analyze the intestinal microflora of mouse cecal contents. Results Supplementation with PnEO (50 and 200?mg/kg) increased colon length and improved colon histopathology . PnEO regulated inflammatory responses by downregulating TLR4/MAPKs activation, thereby reducing the release of cytokines and mediators. Moreover, it also protected the intestinal barrier through enhancing the expression of claudin-1, claudin-3, occludin , ZO-1, and mucin 2 . 16S rRNA gene sequencing revealed that PnEO (200?mg/kg) decreased the abundance of Akkermansia in the gut microbiome . Conclusion PnEO treatment (50 and 200?mg/kg) relieved DSS-induced colitis by inhibiting TLR4/MAPK pathway and protecting intestinal barrier, and high-dose PnEO exhibited better effects. Moreover, PnEO (200?mg/kg) regulated key compositions of the gut microbiome, which indicated that it had therapeutic potential for sustaining gut health to lower the risk of colitis.
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