Department of Cardiology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China.
Phytother Res. 2013 Sep;27(9):1321-7. doi: 10.1002/ptr.4863. Epub 2012 Nov 7.
Curcumin, the principal active component of turmeric, has long been used to treat various diseases in India and China. Recent studies show that curcumin can serve as a therapeutic agent for autoimmune diseases via a variety of mechanisms. Effector memory T cells (T(EM), CCR7⁻ CD45RO⁺ T lymphocyte) have been demonstrated to play a crucial role in the pathogenesis of T cell-mediated autoimmune diseases, such as multiple sclerosis (MS) or rheumatoid arthritis (RA). Kv1.3 channels are predominantly expressed in T(EM) cells and control T(EM) activities. In the present study, we examined the effect of curcumin on human Kv1.3 (hKv1.3) channels stably expressed in HEK-293 cells and its ability to inhibit proliferation and cytokine secretion of T(EM) cells isolated from patients with MS or RA. Curcumin exhibited a direct blockage of hKv1.3 channels in a time-dependent and concentration-dependent manner. Moreover, the activation curve was shifted to a more positive potential, which was consistent with an open-channel blockade. Paralleling hKv1.3 inhibition, curcumin significantly inhibited proliferation and interferon-γ secretion of T(EM) cells. Our findings demonstrate that curcumin is able to inhibit proliferation and proinflammatory cytokine secretion of T(EM) cells probably through inhibition of hKv1.3 channels, which contributes to the potency of curcumin for the treatment of autoimmune diseases. This is probably one of pharmacological mechanisms of curcumin used to treat autoimmune diseases.
姜黄素是姜黄的主要活性成分,长期以来一直被用于治疗印度和中国的各种疾病。最近的研究表明,姜黄素可以通过多种机制作为治疗自身免疫性疾病的药物。效应记忆 T 细胞(T(EM),CCR7⁻ CD45RO⁺ T 淋巴细胞)已被证明在 T 细胞介导的自身免疫性疾病(如多发性硬化症(MS)或类风湿性关节炎(RA))的发病机制中发挥关键作用。Kv1.3 通道主要在 T(EM)细胞中表达,并控制 T(EM)细胞的活性。在本研究中,我们研究了姜黄素对稳定表达于 HEK-293 细胞中的人 Kv1.3(hKv1.3)通道的影响,以及其抑制从 MS 或 RA 患者中分离出的 T(EM)细胞增殖和细胞因子分泌的能力。姜黄素以时间和浓度依赖的方式直接阻断 hKv1.3 通道。此外,激活曲线向更正的电位移动,与开放通道阻断一致。与 hKv1.3 抑制平行,姜黄素显著抑制 T(EM)细胞的增殖和干扰素-γ分泌。我们的研究结果表明,姜黄素能够抑制 T(EM)细胞的增殖和促炎细胞因子分泌,可能是通过抑制 hKv1.3 通道,这有助于姜黄素治疗自身免疫性疾病的功效。这可能是姜黄素用于治疗自身免疫性疾病的药理学机制之一。