Umbelliferone ameliorates ulcerative colitis induced by acetic acid via modulation of TLR4/NF-κB-p65/iNOS and SIRT1/PPARγ signaling pathways in rats
2022
Abdel-Wahab, Basel A. | Alkahtani, Saad A. | Alqahtani, Abdulsalam A. | Hassanein, Emad H. M.
Ulcerative colitis (UC) is a common chronic, idiopathic inflammatory bowel disease associated with inflammatory perturbation and oxidative stress. Umbelliferone (UMB) is a potent anti-inflammatory and antioxidant coumarin derivative. Depending on the possible mechanisms, we aimed to explore and elucidate the therapeutic potential of UMB on UC-inflammatory response and oxidative injury-induced via intrarectal administration of acetic acid (AA) in rats. Animals were assigned into four groups: control group, UMB (30 mg/kg, oral)-treated group, AA-induced colitis model group (2 ml of AA; 3% v/v), and colitis treated with UMB group. The results showed that UMB improved macroscopic and histological tissue injury caused by the AA. Mechanistically, UMB reduced the elevated colonic TNF-α, IL-6, MPO, and VCAM-1 and downregulated the gene and protein expression of TLR4, NF-κB, and iNOS signaling factors, exhibiting potent anti-inflammatory effects. Moreover, UMB upregulated the gene and protein expression of both SIRT1 and PPARγ signaling pathways, thereby inhibiting both oxidative injury and inflammatory response. Conclusively, UMB protected rats against AA-induced UC by suppressing the TLR4/NF-κB-p65/iNOS signaling pathway and promoting the SIRT1/PPARγ signaling. Our results showed the effectiveness of UMB in alleviating the pathogenesis of UC and introduced it as a possible therapeutic applicant for clinical application.
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