Targeting Nrf2/HO-1 signaling by crocin: Role in attenuation of AA-induced ulcerative colitis in rats
Targeting Nrf2/HO-1 signaling by crocin: Role in attenuation of AA-induced ulcerative colitis in rats
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DOI：
10.1016/j.biopha.2018.11.133
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发表时间：
2019-02-01
影响因子：
7.5
通讯作者：
Salem, Hatem A.
中科院分区：
文献类型：
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作者：
Khodir, Ahmed E.;Said, Eman;Salem, Hatem A.
溃疡性结肠炎 (UC) 通常是一种轻度活动性疾病；然而，它可能与严重的全身并发症有关。目前的研究旨在评估藏红花素的抗溃疡和结肠保护特性；藏红花的主要生物活性成分通过结肠内滴注 AA (AA) 来对抗实验诱导的 UC。大鼠连续 8 天口服非洛地平 (3 mg/kg) 或藏红花素 (20 mg/kg) 作为保护性和治疗性疗法。无论是作为保护性药物还是治疗性药物，藏红花素都能显着逆转 AA 引起的结肠损伤。结肠内 AA 诱导显着的功能性、生化性和炎症性结肠损伤。另一方面，藏红花素显着减弱 AA 诱导的氧化、炎症和细胞凋亡活性。藏红花素显着增强结肠抗氧化防御，降低结肠肿瘤坏死因子-α (TNF-α) 和 Ca + 2 含量，并下调炎症反应和氧化负荷。藏红花素的抗溃疡作用似乎是 Ca + 2 依赖性的。最重要的是，藏红花素增强结肠核因子、红细胞衍生 2 样蛋白 2 (Nrf2) 含量和血红素加氧酶-1 (HO-1) 活性，并减弱 caspase-3 活性。综上所述;藏红花素具有抗溃疡和结肠保护作用，主要通过其抗氧化、抗炎和抗细胞凋亡特性介导。治疗效果主要是通过结肠 Nrf2 含量在保护方案中增强 211%、在治疗方案中增强 350% 以及 HO-1 信号传导在保护方案中增强 49%、在治疗方案中增强 288% 来介导的。 Nrf2 和 HO-1 信号传导的增强以及 caspase-3 活性的下调被认为是观察到的治疗效果的基础。
Ulcerative colitis (UC) is usually a mildly active disease; however, it can be associated with serious systemic complications. The current study was undertaken to evaluate the anti-ulcerogenic and coloprotective properties of crocin; the major biologically active ingredient of saffron against experimentally-induced UC, by intracolonic instillation of AA (AA). Rats received either felodipine (3 mg/kg) or crocin (20 mg/kg) orally for 8 successive days as protective and curative therapies. Either as a protective or as a curative remedy, crocin significantly reversed AA-induced colonic damage. Intracolonic AA-induced a significant functional, biochemical and inflammatory colon injury. On the other hand, crocin significantly attenuated AA-induced oxidative, inflammatory and apoptotic activity. Crocin significantly enhanced colon anti-oxidant defenses and reduced colon tumor necrosis factor-alpha (TNF-alpha) and Ca + 2 contents with down-regulation of the inflammatory response and oxidative load. The anti-ulcerogenic effect of crocin appears to be Ca + 2 dependent Most importantly, crocin enhanced colon Nuclear Factor, Erythroid-Derived 2 like Protein 2 (Nrf2) content and Heme Oxygenase-1 (HO-1) activity and attenuated caspase-3 activity. In conclusion; crocin demonstrated anti-ulcerogenic and coloprotective effect mediated primarily by its antioxidant, anti-inflammatory and anti-apoptotic properties. The therapeutic impact is mediated primarily via enhancement of colon Nrf2 content by 211% in protective protocol and by 350% in curative and HO-1 signaling by 49% in protective protocol and, 288% in the curative protocol. Enhancement of Nrf2 and HO-1 signaling and down-regulation of caspase-3 activity are believed to underly the observed therapeutic effect.