Abstract
Pistacia lentiscus L. (PL) is a flowering plant traditionally used in the treatment of gastrointestinal disorders. The extracts of this plant are endowed with strong pharmacological activities. The aim of our current study was to investigate the anti-inflammatory and potential therapeutic effects of PL leaves aqueous extract (PLAE) against Dextran Sulfate Sodium (DSS)-induced acute colitis. The therapeutic effect of PLAE was evaluated after orally administration of 3% DSS alone or concomitantly with PLAE (50, 100 or 200mg/Kg). Mucosal lesions were assessed by macroscopic and histopathological examination. In this context, hemorrhage, diarrhea, weight loss, and disease activity index (DAI) were determined daily throughout the experiment. In the same way, hematoxylin-eosin and Alcian blue staining of colonic mucosal were used to evaluate, respectively, mucosal damages and mucus production. Furthermore, the levels of nitric oxide (NO), and pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] were measured in plasma, as well as in colonic explants and peritoneal macrophages cultures supernatants. Administration of DSS + PLAE indicated a significant reduction in clinical score of acute colitis DAI compared to DSS alone administration. Interestingly, histological analysis of the mucosa showed that DSS + PLAE-treated groups exhibited almost normal histology evidenced by an intact epithelium structure and less inflammatory cell infiltration in the mucosa. Alcian bleu staining revealed that DSS + PLAE-treated groups displayed almost normal mucus production. Importantly, a significant decrease in pro-inflammatory mediators (NO, IL-6 and TNF-α) levels in dose-dependent manner was reported in plasma, and culture supernatants of colonic explants and peritoneal macrophages from DSS + PLAE-treated mice compared to the DSS group. Our results showed that the systemic and local anti-inflammatory activities of aqueous leaves extract of PL improve the clinical signs of acute colitis. Our data suggest that PLAE has beneficial effects and could constitute a promising approach against acute ulcerative colitis by targeting the deregulated immune response.
Highlights
Inflammatory bowel disease (IBD) constitute a group of chronic and relapsing idiopathic inflammatory disorder of the intestine that include Crohn's disease (CD) and ulcerative colitis (UC) (Caruso et al 2020, Geboes et al 2018)
A significant decrease in pro-inflammatory mediators (NO, IL-6 and tumor necrosis factor-α (TNF-α)) levels in dose dependent manner was reported in plasma, and culture supernatants of colonic explants and peritoneal macrophages from Dextran Sulfate Sodium (DSS)+ PL leaves aqueous extract (PLAE)-treated mice compared to the DSS group
- Induces a significant decrease in pro-inflammatory mediators (NO, IL-6 and TNF-α) levels in plasma, and culture supernatants of colonic explants and peritoneal macrophages
Summary
Inflammatory bowel disease (IBD) constitute a group of chronic and relapsing idiopathic inflammatory disorder of the intestine that include Crohn's disease (CD) and ulcerative colitis (UC) (Caruso et al 2020, Geboes et al 2018). The pathogenesis of both Crohn’s disease and ulcerative colitis involves intestinal inflammation, these two disorders differ in several features, including the association with specific susceptibility loci and the type of immune response and pathology associated with disease (McGovern et al 2015). The intestine of patients with IBD is massively infiltrated by inflammatory cells, mostly macrophages and neutrophils that release large amounts of pro-inflammatory cytokines, such as TNF-α, IL-6, IL-17, IL-12, and interferon-γ (Abraham and Medzhitov 2011, Soufli et al 2016, Toumi et al 2021). The aim of our current study was to investigate the anti-inflammatory and potential therapeutic effects of PL leaves aqueous extract (PLAE) against Dextran Sulfate Sodium (DSS)-induced acute colitis
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