Martín Antonio Ramón, Villegas Isabel, Sánchez-Hidalgo Marina, de la Lastra Catalina Alarcón
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Profesor García González Street 2, Sevilla 41012, Spain.
Br J Pharmacol. 2006 Apr;147(8):873-85. doi: 10.1038/sj.bjp.0706469.
Neutrophil infiltration, proinflammatory cytokines, eicosanoid generation and oxidative stress have been implicated in colitis. Resveratrol is a polyphenolic compound found in grapes and wine, with multiple pharmacological actions, including anti-inflammatory, antioxidant, antitumour and immunomodulatory activities. In a previous report, we documented that resveratrol decreases the degree of inflammation associated with acute experimental colonic inflammation, but its effects on chronic experimental colitis remain undetermined. The aim of this research was to investigate the effects of resveratrol on the chronic colonic injury caused by intracolonic instillation of trinitrobenzenesulphonic acid (TNBS) in rats. The inflammatory response was assessed by histology and myeloperoxidase activity. Tumour necrosis factor alpha (TNF-alpha) production, histological and histochemical analysis of the lesions were also carried out. We determined the production of prostaglandin (PG) E2 and D2 in colon mucosa, as well as cyclooxygenase (COX)-1 and -2 and nuclear transcription factor NF-kappa B (NF-kappaB) p65 protein expression. Finally, since resveratrol has been found to modulate apoptosis, we intended to elucidate its effects on colonic mucosa under chronic inflammatory conditions. Resveratrol (10 mg kg(-1) day(-1)) significantly attenuated the damage score and corrected the disturbances in morphology associated to injury. In addition, the degree of neutrophil infiltration and the levels of TNF-alpha were significantly ameliorated. Resveratrol did not modify PGD2 levels but returned the decreased PGE2 values to basal levels and also reduced COX-2 and the NF-kappaB p65 protein expression. Furthermore, treatment of rats with resveratrol caused a significant increase of TNBS-induced apoptosis in colonic cells. In conclusion, resveratrol reduces the damage in chronic experimentally induced colitis, alleviates the oxidative events, returns PGE2 production to basal levels and stimulates apoptosis in colonic cells.
中性粒细胞浸润、促炎细胞因子、类花生酸生成和氧化应激与结肠炎有关。白藜芦醇是一种存在于葡萄和葡萄酒中的多酚化合物，具有多种药理作用，包括抗炎、抗氧化、抗肿瘤和免疫调节活性。在之前的一份报告中，我们记录了白藜芦醇可降低与急性实验性结肠炎症相关的炎症程度，但其对慢性实验性结肠炎的影响仍未确定。本研究的目的是探讨白藜芦醇对大鼠结肠内注入三硝基苯磺酸（TNBS）所致慢性结肠损伤的影响。通过组织学和髓过氧化物酶活性评估炎症反应。还进行了肿瘤坏死因子α（TNF-α）产生、病变的组织学和组织化学分析。我们测定了结肠黏膜中前列腺素（PG）E2和D2的产生，以及环氧化酶（COX）-1和-2和核转录因子NF-κB（NF-κB）p65蛋白表达。最后，由于已发现白藜芦醇可调节细胞凋亡，我们旨在阐明其在慢性炎症条件下对结肠黏膜的影响。白藜芦醇（10 mg kg⁻¹ 天⁻¹）显著降低了损伤评分，并纠正了与损伤相关的形态学紊乱。此外，中性粒细胞浸润程度和TNF-α水平显著改善。白藜芦醇未改变PGD2水平，但使降低的PGE2值恢复到基础水平，还降低了COX-2和NF-κB p65蛋白表达。此外，用白藜芦醇治疗大鼠导致TNBS诱导的结肠细胞凋亡显著增加。总之，白藜芦醇可减轻慢性实验性诱导结肠炎的损伤，减轻氧化事件，使PGE2产生恢复到基础水平，并刺激结肠细胞凋亡。
