Patchouli alcohol alleviates ulcerative colitis in mice by targeting PDI to reduce ER stress and inflammation

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) marked by mucosal damage and impaired epithelial barrier function. Current treatments often fall short, necessitating novel therapeutic strategies. Endoplasmic reticulum (ER) stress and inflammation are key drivers of UC pathology, contributing to intestinal epithelial injury. Natural compounds like Patchouli alcohol (PA) with known anti-inflammatory and antioxidant properties offer a promising avenue, but their precise mechanisms in UC, particularly regarding ER stress modulation, require further elucidation.

Researchers investigated Patchouli alcohol (PA) in a dextran sulfate sodium (DSS)-induced ulcerative colitis mouse model to assess its therapeutic effects. They also used an LPS-induced inflammatory model in RAW264.7 cells to explore cellular mechanisms. Primary endpoints included assessment of UC symptoms, intestinal barrier integrity, inflammatory markers, and ER stress pathways. The study identified protein disulfide isomerase (PDI) as a direct target of PA and evaluated its impact on IRE1 activation.

Patchouli alcohol (PA) significantly alleviated symptoms of DSS-induced ulcerative colitis in mice, demonstrating a clear therapeutic effect. This was accompanied by a reduction in intestinal barrier impairment and inhibition of inflammatory reactions. > In LPS-induced RAW264.7 cells, PA significantly downregulated the mRNA expression of il-1β and il-6, indicating its potent anti-inflammatory action at the cellular level. Mechanistically, protein disulfide isomerase (PDI) was identified as a direct molecular target of PA. By inhibiting IRE1 activation via PDI, PA effectively mitigated endoplasmic reticulum (ER) stress. This reduction in ER stress was crucial in preventing intestinal epithelial injury, thereby contributing to the overall alleviation of UC severity. The protective effect on the intestinal epithelial barrier was directly linked to PA's specific targeting of PDI and subsequent ER stress alleviation.