Inflammatory bowel disease, comprising
Crohn's disease (CD) and
ulcerative colitis (UC), is often debilitating. The disease etiology is multifactorial, involving
genetic susceptibility, microbial dysregulation, abnormal immune activation, and environmental factors. Currently, available
drug therapies are associated with adverse effects when used long-term. Therefore, the search for new drug candidates to treat IBD is imperative. The
peroxisome proliferator-activated receptor-γ (PPARγ) is highly expressed in the colon. PPARγ plays a vital role in regulating colonic
inflammation.
1,8-cineole, also known as
eucalyptol, is a
monoterpene oxide present in various aromatic plants which possess potent anti-inflammatory activity. Molecular docking and dynamics studies revealed that
1,8-cineole binds to PPARγ and if it were an agonist, that would explain the anti-inflammatory effects of
1,8-cineole. Therefore, we investigated the role of
1,8-cineole in colonic
inflammation, using both in vivo and in vitro experimental approaches.
Dextran sodium sulfate (DSS)-induced
colitis was used as the in vivo model, and
tumor necrosis factor-α (TNFα)-stimulated HT-29 cells as the in vitro model.
1,8-cineole treatment significantly decreased the inflammatory response in DSS-induced
colitis mice.
1,8-cineole treatment also increased nuclear factor erythroid 2-related factor 2 (Nrf2) translocation into the nucleus to induce potent
antioxidant effects.
1,8-cineole also increased colonic PPARγ
protein expression. Similarly,
1,8-cineole decreased proinflammatory
chemokine production and increased PPARγ
protein expression in TNFα-stimulated HT-29 cells.
1,8-cineole also increased PPARγ promoter activity time-dependently. Because of its potent anti-inflammatory effects,
1,8-cineole may be valuable in treating IBD.