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p-Cymene and Rosmarinic Acid Ameliorate TNBS-Induced Intestinal Inflammation Upkeeping ZO-1 and MUC-2: Role of Antioxidant System and Immunomodulation

1
Postgraduate Program in Natural and Synthetic Bioactive Products, Health Sciences Center, Federal University of Paraíba (UFPB), João Pessoa 58051970, Brazil
2
Department of Biophysics and Pharmacology, Biosciences Center, Federal University of Rio Grande do Norte, Natal 59064-741, Brazil
3
Department of Morphology, Histology and Basic Pathology, Biosciences Center, Federal University of Rio Grande do Norte, Natal 59064-741, Brazil
4
Department of Pharmacology, Federal University of Santa Catarina (UFSC), Florianópolis 88037-000, Brazil
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(16), 5870; https://doi.org/10.3390/ijms21165870
Received: 16 May 2020 / Revised: 4 June 2020 / Accepted: 11 June 2020 / Published: 15 August 2020
(This article belongs to the Section Molecular Pharmacology)
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. View Full-Text
Keywords: p-cymene; rosmarinic acid; intestinal inflammation; antioxidant; immunomodulation; cytoprotection p-cymene; rosmarinic acid; intestinal inflammation; antioxidant; immunomodulation; cytoprotection
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MDPI and ACS Style

Formiga, R.d.O.; Alves Júnior, E.B.; Vasconcelos, R.C.; Guerra, G.C.B.; Antunes de Araújo, A.; Carvalho, T.G.d.; Garcia, V.B.; de Araújo Junior, R.F.; Gadelha, F.A.A.F.; Vieira, G.C.; Sobral, M.V.; Barbosa Filho, J.M.; Spiller, F.; Batista, L.M. p-Cymene and Rosmarinic Acid Ameliorate TNBS-Induced Intestinal Inflammation Upkeeping ZO-1 and MUC-2: Role of Antioxidant System and Immunomodulation. Int. J. Mol. Sci. 2020, 21, 5870. https://doi.org/10.3390/ijms21165870

AMA Style

Formiga RdO, Alves Júnior EB, Vasconcelos RC, Guerra GCB, Antunes de Araújo A, Carvalho TGd, Garcia VB, de Araújo Junior RF, Gadelha FAAF, Vieira GC, Sobral MV, Barbosa Filho JM, Spiller F, Batista LM. p-Cymene and Rosmarinic Acid Ameliorate TNBS-Induced Intestinal Inflammation Upkeeping ZO-1 and MUC-2: Role of Antioxidant System and Immunomodulation. International Journal of Molecular Sciences. 2020; 21(16):5870. https://doi.org/10.3390/ijms21165870

Chicago/Turabian Style

Formiga, Rodrigo d.O.; Alves Júnior, Edvaldo B.; Vasconcelos, Roseane C.; Guerra, Gerlane C.B.; Antunes de Araújo, Aurigena; Carvalho, Thaís G.d.; Garcia, Vinícius B.; de Araújo Junior, Raimundo F.; Gadelha, Francisco A.A.F.; Vieira, Giciane C.; Sobral, Marianna V.; Barbosa Filho, José M.; Spiller, Fernando; Batista, Leônia M. 2020. "p-Cymene and Rosmarinic Acid Ameliorate TNBS-Induced Intestinal Inflammation Upkeeping ZO-1 and MUC-2: Role of Antioxidant System and Immunomodulation" Int. J. Mol. Sci. 21, no. 16: 5870. https://doi.org/10.3390/ijms21165870

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