Abstract
p-Cymene (p-C) and rosmarinic acid (RA) are secondary metabolites that are present in medicinal herbs and Mediterranean spices that have promising anti-inflammatory properties. This study aimed to evaluate their intestinal anti-inflammatory activity in the trinitrobenzene sulphonic acid (TNBS)-induced colitis model in rats. p-C and RA (25–200 mg/kg) oral administration reduced the macroscopic lesion score, ulcerative area, intestinal weight/length ratio, and diarrheal index in TNBS-treated animals. Both compounds (200 mg/kg) decreased malondialdehyde (MDA) and myeloperoxidase (MPO), restored glutathione (GSH) levels, and enhanced fluorescence intensity of superoxide dismutase (SOD). They also decreased interleukin (IL)-1β and tumor necrosis factor (TNF)-α, and maintained IL-10 basal levels. Furthermore, they modulated T cell populations (cluster of differentiation (CD)4+, CD8+, or CD3+CD4+CD25+) analyzed from the spleen, mesenteric lymph nodes, and colon samples, and also decreased cyclooxigenase 2 (COX-2), interferon (IFN)-γ, inducible nitric oxide synthase (iNOS), and nuclear transcription factor kappa B subunit p65 (NFκB-p65) mRNA transcription, but only p-C interfered in the suppressor of cytokine signaling 3 (SOCS3) expression in inflamed colons. An increase in gene expression and positive cells immunostained for mucin type 2 (MUC-2) and zonula occludens 1 (ZO-1) was observed. Altogether, these results indicate intestinal anti-inflammatory activity of p-C and RA involving the cytoprotection of the intestinal barrier, maintaining the mucus layer, and preserving communicating junctions, as well as through modulation of the antioxidant and immunomodulatory systems.
Highlights
Inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD), are a group of recurrent and debilitating disorders [1,2]
The release of cytokines contributes to the overproduction of reactive oxygen species (ROS) and the impairment of endogenous antioxidant mechanisms promoted by glutathione (GSH), superoxide dismutase (SOD), and other molecules, being tightly involved with the development of tissue injury [16]
Considering the pharmacological potential of p-C and rosmarinic acid (RA) and the lack of studies evaluating the effects of these isolated compounds in IBD models, we aimed to assess their effects on the outcome of trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis
Summary
Inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD), are a group of recurrent and debilitating disorders [1,2]. UC displays colon-restricted lesions that appear continuously on mucosa and submucosa layers characterized by a Th2-like and natural killer T cell (NKT) phenotype [7,8,9,10], accompanied by neutrophil infiltration into the lamina propria; edema; increased T cell reactivity; and depletion of mucins, such as mucin-type 2 (MUC-2) [11,12,13] This results in instabilities of the intestinal barrier structure formed by epithelial cells that are connected by tight junction structural proteins (claudin, occludin, zonula occludes, etc.) [14]. These miscellaneous pathological changes result in common clinical manifestations including anal lesions, rectal bleeding, diarrhea, lower abdominal pain, and tenesmus, which dramatically impact quality of life [17]
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