Cinnamaldehyde targets TLR-4 and inflammatory mediators in acetic-acid induced ulcerative colitis model

Cinnamon and its bioactive ingredients such as cinnamaldehyde (CA), with broad pharmacological profiles, are important parts of daily diet in many cultures. Moreover, there are plenty motivating patents on efficacy of nutritional phytochemicals as novel anti-inflammatory drugs in patients with inflammatory bowel disease (IBD). This study intended to evaluate the effects of CA on inflammatory biomarkers in acetic acid-induced colitis rats. Colitis was induced in all animals, except in sham group, using acetic acid (4%). Following colitis induction, in 3 groups, CA was administrated orally at 2, 4 and 8 mg/kg/day for 2 days (once a day). Other groups were defined as the control (only treated with acetic acid), sham group (normal saline), and a standard group (Dexamethasone). To evaluate the inflammation sites, macroscopic and microscopic markers were assessed. Tissue concentrations of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF)-α, were assessed by ELISA assay kits, while myeloperoxidase (MPO) was measured spectrophotometrically. The mRNA expression of toll like receptor (TLR)-4 in colon tissue was assessed by Real time-PCR. CA at 4 mg/kg/day and 8 mg/kg/day significantly improved microscopic and macroscopic manifestations of colitis tissues. TNF-α, MPO, and IL-6 levels were significantly lower in CA treated groups at all the concentrations tested (P < 0.001). CA at 4 and 8 mg/kg/day significantly downregulated the mucosal gene expression of TLR-4. CA attenuated experimental colitis by means of colitis symptoms, reduction in inflammation cytokines, decline of neutrophil infiltration, and suppression of TLR-4 expression in acetic acid-induced colitis. CA improved colitis in animal model through suppression of inflammatory parameters and downregulation of TLR-4 mRNA expression.