Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86057-970, Cx Postal 10.011, Londrina, Paraná, Brazil.
Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Hospital Universitário, Universidade Estadual de Londrina, Av. Robert Koch, 60, 86038-350, Londrina, Paraná, Brazil.
Inflammation. 2018 Aug;41(4):1276-1289. doi: 10.1007/s10753-018-0776-9.
The idiopathic inflammatory bowel diseases (IBD) comprise two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis. Recruited neutrophils and macrophages contribute to intestinal tissue damage via production of ROS and NF-κB-dependent pro-inflammatory cytokines. The introduction of anti-TNF-α therapies in the treatment of IBD patients was a seminal advance. This therapy is often limited by a loss of efficacy due to the development of adaptive immune response, underscoring the need for novel therapies targeting similar pathways. Vinpocetine is a nootropic drug and in addition to its antioxidant effect, it is known to have anti-inflammatory and analgesic properties, partly by inhibition of NF-κB and downstream cytokines. Therefore, the present study evaluated the effect of the vinpocetine in a model of acid acetic-induced colitis in mice. Treatment with vinpocetine reduced edema, MPO activity, microscopic score and macroscopic damage, and visceral mechanical hyperalgesia. Vinpocetine prevented the reduction of colonic levels of GSH, ABTS radical scavenging ability, and normalized levels of anti-inflammatory cytokine IL-10. Moreover, vinpocetine reduced NF-κB activation and thereby NF-κB-dependent pro-inflammatory cytokines IL-1β, TNF-α, and IL-33 in the colon. Thus, we demonstrate for the first time that vinpocetine has anti-inflammatory, antioxidant, and analgesic effects in a model of acid acetic-induced colitis in mice and deserves further screening to address its suitability as an approach for the treatment of IBD.
特发性炎症性肠病（IBD）包括两种慢性肠道疾病：克罗恩病和溃疡性结肠炎。募集的中性粒细胞和巨噬细胞通过产生 ROS 和 NF-κB 依赖性促炎细胞因子导致肠道组织损伤。抗 TNF-α 疗法在 IBD 患者中的引入是一个开创性的进展。这种治疗方法常常由于适应性免疫反应的发展而导致疗效丧失，这凸显了需要针对类似途径的新型治疗方法。长春西汀是一种益智药，除了具有抗氧化作用外，它还具有抗炎和镇痛作用，部分通过抑制 NF-κB 和下游细胞因子。因此，本研究评估了长春西汀在乙酸诱导的小鼠结肠炎模型中的作用。长春西汀治疗可减轻水肿、MPO 活性、显微镜评分和宏观损伤，并减轻内脏机械性痛觉过敏。长春西汀可防止结肠中 GSH 水平、ABTS 自由基清除能力和抗炎细胞因子 IL-10 水平降低。此外，长春西汀可降低 NF-κB 的激活，从而降低结肠中 NF-κB 依赖性促炎细胞因子 IL-1β、TNF-α 和 IL-33。因此，我们首次证明长春西汀在乙酸诱导的小鼠结肠炎模型中具有抗炎、抗氧化和镇痛作用，值得进一步筛选，以确定其作为治疗 IBD 的方法的适用性。
