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用于预防口腔头颈部鳞状细胞癌的姜黄素胶制剂

Curcumin gum formulation for prevention of oral cavity head and neck squamous cell carcinoma.

作者信息

Boven Lindsay, Holmes Sean P, Latimer Brian, McMartin Kenneth, Ma Xiaohui, Moore-Medlin Tara, Khandelwal Alok R, McLarty Jerry, Nathan Cherie-Ann O

机构信息

Department of Otolaryngology-Head and Neck Surgery, Louisiana State University- Health Sciences Center, Shreveport, Louisiana, U.S.A.

Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University- Health Sciences Center, Shreveport, Louisiana, U.S.A.

出版信息

Laryngoscope. 2019 Jul;129(7):1597-1603. doi: 10.1002/lary.27542. Epub 2018 Nov 13.

Abstract

OBJECTIVES/HYPOTHESIS: Head and neck squamous cell carcinoma represents the sixth most common cancer. As a result of field cancerization, second primaries and recurrences are high. Hence, research has focused on chemoprevention. Curcumin, a polyphenol compound with anticarcinogenic properties, is one such promising nutraceutical. As poor bioavailability limits curcumin's use, a novel gum formulation was tested allowing for direct mucosal absorption into the bloodstream. This preliminary study validates curcumin gum efficacy by assessing release and transmucosal absorption, along with measuring its effects on serum cytokine levels.

STUDY DESIGN

Clinical trial.

METHODS

Protocols consisting of initial chew (chewing gum for 30 minutes) and revised chew (alternating chewing and parking gum against buccal mucosa for 30 minutes) were tested in healthy volunteers. High-performance liquid chromatography measured remnant curcumin in chewed gum, serum, and saliva. Serum levels were assayed for 15 proinflammatory cytokines via multiplex analysis.

RESULTS

Revised chew samples demonstrated significantly higher curcumin release and absorption (P = .0078). Curcumin serum levels were significantly higher at 4 hours in samples > 2.0 g of curcumin release (P = .01). As saliva levels decreased, a concurrent increase in serum levels was observed, with no significance in the inverse relationship (P = .1423). When evaluating differences between gender, race, and age, the Asian population showed significantly lower curcumin release and serum levels (P = .009). CXCL1 (GRO-α) and TNF-α were significantly decreased in serum after chewing the gum (P = .036, P < .001, respectively).

CONCLUSIONS

Enhanced mucosal contact appears critical in improving curcumin release and absorption. CXCL1 and TNF-α both represent potential biomarkers for the future study of curcumin chemoprevention.

LEVEL OF EVIDENCE

2b Laryngoscope, 129:1597-1603, 2019.

摘要

目的/假设:头颈部鳞状细胞癌是第六大常见癌症。由于场癌化作用,第二原发癌和复发率很高。因此,研究集中在化学预防上。姜黄素是一种具有抗癌特性的多酚化合物,是一种很有前景的营养保健品。由于生物利用度差限制了姜黄素的应用,一种新型口香糖制剂经过测试,可使其直接经黏膜吸收进入血液。这项初步研究通过评估释放和经黏膜吸收情况,并测量其对血清细胞因子水平的影响,验证了姜黄素口香糖的疗效。

研究设计

临床试验。

方法

在健康志愿者中测试了由初始咀嚼(咀嚼口香糖30分钟)和改良咀嚼(交替咀嚼并将口香糖贴在颊黏膜上30分钟)组成的方案。采用高效液相色谱法测定咀嚼后的口香糖、血清和唾液中残留的姜黄素。通过多重分析测定血清中15种促炎细胞因子的水平。

结果

改良咀嚼样本显示姜黄素的释放和吸收显著更高(P = 0.0078)。姜黄素释放量>2.0 g的样本在4小时时血清水平显著更高(P = 0.01)。随着唾液水平下降,观察到血清水平同时升高,两者呈负相关但无显著性差异(P = 0.1423)。在评估性别、种族和年龄之间的差异时,亚洲人群的姜黄素释放和血清水平显著较低(P = 0.009)。咀嚼口香糖后血清中的CXCL1(GRO-α)和TNF-α显著降低(分别为P = 0.036,P < 0.001)。

结论

增强黏膜接触对于改善姜黄素的释放和吸收似乎至关重要。CXCL1和TNF-α均代表未来姜黄素化学预防研究的潜在生物标志物。

证据水平

2b 《喉镜》,2019年,第129卷,第1597 - 1603页

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