Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
Mol Nutr Food Res. 2010 Aug;54(8):1202-9. doi: 10.1002/mnfr.200900106.
Chronic and complex autoimmune diseases, currently treated palliatively with immunosuppressives, require multi-targeted therapy for greater effectiveness. The naturally occurring polyphenol curcumin has emerged as a powerful "nutraceutical" that interacts with multiple targets to regress diseases safely and inexpensively. Up to 8 g/day of curcumin for 18 months was non-toxic to humans. However, curcumin's utility is limited by its aqueous insolubility. We have demonstrated a heat-mediated 12-fold increase in curcumin's aqueous solubility. Here, we show by SDS-PAGE and surface plasmon resonance that heat-solubilized curcumin binds to proteins. Based on this binding we hypothesized that heat-solubilized curcumin or turmeric would prevent autoantibody targeting of cognate autoantigens. Heat-solubilized curcumin/turmeric significantly decreased binding of autoantibodies from Sjögren's syndrome (up to 43/70%, respectively) and systemic lupus erythematosus (up to 52/70%, respectively) patients as well as an animal model of Sjögren's syndrome (up to 50/60%, respectively) to their cognate antigens. However, inhibition was not specific to autoimmunity. Heat-solubilized curcumin/turmeric also inhibited binding of commercial polyclonal anti-spectrin to spectrin (50/56%, respectively). Thus, we suggest that the multifaceted heat-solubilized curcumin can ameliorate autoimmune disorders. In addition, the non-toxic curcumin could serve as a new protein stain in SDS-PAGE even though it is less sensitive than the Coomassie system which involves toxic chemicals.
慢性和复杂的自身免疫性疾病目前通过免疫抑制剂进行姑息治疗,需要多靶点治疗以提高疗效。天然存在的多酚姜黄素已成为一种强大的“营养保健品”,可通过多种靶点相互作用,安全且廉价地使疾病消退。高达 8 克/天的姜黄素用于人类 18 个月是无毒的。然而,姜黄素的用途受到其水溶性差的限制。我们已经证明姜黄素的水溶解度通过热介导增加了 12 倍。在这里,我们通过 SDS-PAGE 和表面等离子体共振显示,热溶解的姜黄素与蛋白质结合。基于这种结合,我们假设热溶解的姜黄素或 turmeric 将防止自身抗体针对同源自身抗原。热溶解的姜黄素/ turmeric 显著降低了来自干燥综合征(分别高达 43/70%)和系统性红斑狼疮(分别高达 52/70%)患者以及干燥综合征动物模型的自身抗体与同源抗原的结合(分别高达 50/60%)。然而,抑制并非特异性针对自身免疫。热溶解的姜黄素/ turmeric 还抑制了商业多克隆抗血影蛋白与血影蛋白的结合(分别为 50/56%)。因此,我们认为多方面的热溶解姜黄素可以改善自身免疫性疾病。此外,即使姜黄素比涉及有毒化学物质的考马斯亮蓝系统的灵敏度低,无毒的姜黄素也可以作为 SDS-PAGE 中的新型蛋白质染色剂。