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姜黄素作为癌症患者潜在抗黏膜炎剂的抗菌和抗炎动力学。

Antibacterial and antiinflammatory kinetics of curcumin as a potential antimucositis agent in cancer patients.

机构信息

Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Bern, Bern, Switzerland.

出版信息

Nutr Cancer. 2012;64(7):975-81. doi: 10.1080/01635581.2012.713161. Epub 2012 Sep 13.

Abstract

The antiinflammatory agent curcumin (diferuloylmethane) has a potential to mitigate cancer therapy-induced mucositis. We assessed the in vitro extent of its bactericidal activity and determined the kinetics of its antiinflammatory effect on pharyngeal cells. Bactericidal activity was assessed using the LIVE/DEAD® Kit after 4 h of exposure to curcumin (50-200 μM) in 18 oropharyngeal species commonly associated with bacteremia in febrile neutropenia. Moraxella catarrhalis or its outer membrane vesicles were used to determine the inhibitory effect of curcumin on bacteria-induced proinflammatory activity as determined by cytokine release into the supernatant of Detroit 562 pharyngeal cells using the Luminex® xMAP® technology. Curcumin exerted a concentration-dependent bactericidal effect on all 18 species tested. After 4 h at 200 μM, 12 species tested were completely killed. Preincubation of Detroit cells with 200 μM curcumin for 5 to 60 min resulted in complete suppression of the release of tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, granulocyte macrophage-colony stimulating factor, and vascular endothelial growth factor. Fibroblast growth factor-2 and interferon-γ were not affected. Repetitive exposure to curcumin resulted in repetitive suppression of cytokine/chemokine expression lasting from 4 to 6 h. Through reduction of oral microbial density as well as suppression of inflammation cascades curcumin may prevent cancer therapy-induced oral mucositis, e.g., when applied as multiple daily mouth washes.

摘要

抗炎剂姜黄素(二芳基甲烷)具有减轻癌症治疗引起的黏膜炎的潜力。我们评估了其杀菌活性的体外程度,并确定了其对咽细胞抗炎作用的动力学。在 LIVE/DEAD®Kit 中,将姜黄素(50-200μM)暴露于 18 种与发热性中性粒细胞减少症中菌血症相关的常见口咽物种中 4 小时后,评估杀菌活性。使用莫拉氏菌属或其外膜囊泡来确定姜黄素对细菌诱导的促炎活性的抑制作用,方法是使用 Luminex®xMAP®技术将细胞因子释放到 Detroit 562 咽细胞的上清液中。姜黄素对所有 18 种测试的物种均表现出浓度依赖性的杀菌作用。在 200μM 下孵育 4 小时后,12 种测试的物种完全被杀死。用 200μM 姜黄素预处理 Detroit 细胞 5 至 60 分钟可完全抑制肿瘤坏死因子-α、白细胞介素(IL)-6、IL-8、单核细胞趋化蛋白 1、粒细胞巨噬细胞集落刺激因子和血管内皮生长因子的释放。成纤维细胞生长因子-2 和干扰素-γ不受影响。重复暴露于姜黄素可导致细胞因子/趋化因子表达的重复抑制,持续 4 至 6 小时。通过降低口腔微生物密度以及抑制炎症级联反应,姜黄素可能预防癌症治疗引起的口腔黏膜炎,例如,当作为每日多次漱口剂使用时。

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