Combination of curcumin and piperine prevents formation of gallstones in C57BL6 mice fed on lithogenic diet: whether NPC1L1/SREBP2 participates in this process?
Combination of curcumin and piperine prevents formation of gallstones in C57BL6 mice fed on lithogenic diet: whether NPC1L1/SREBP2 participates in this process?
复制标题
姜黄素和胡椒碱的组合可防止喂食生石饮食的 C57BL6 小鼠中胆结石的形成：NPC1L1/SREBP2 是否参与此过程？
DOI：
10.1186/s12944-015-0106-2
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发表时间：
2015-09-03
影响因子：
4.5
通讯作者：
Tian, Yu
中科院分区：
文献类型：
--
作者：
Li, Yongnan;Li, Min;Tian, Yu
背景胆固醇结石的形成是由于胆固醇在胆汁中溶解度的物理化学失衡所导致的胆固醇稳态的破坏。我们早期的研究表明，姜黄素（1000 mg/kg）可以预防胆结石的形成。姜黄素吸收差，胡椒碱是生物利用度增强剂。方法C57 BL 6小鼠用致石饲料喂养4周，同时给予姜黄素500、1000 mg/kg和/或胡椒碱20 mg/kg。记录胆囊结石形成率，并采集血液、胆汁、胆囊、肝脏和小肠标本。计算胆囊体积和肝脏重量，并对血液和胆汁进行生化分析。结果姜黄素与胡椒碱合用可显著增强姜黄素的作用，从而阻止胆囊结石的发生，降低胆汁中胆固醇和血脂的饱和度，结论姜黄素能抑制胆固醇的形成，降低NPC 1 L1和SREBP 2的mRNA和蛋白水平的表达高脂饮食诱发小鼠胆结石，SREBP 2和NPC 1 L1可能参与了这一过程。姜黄碱可以增加姜黄素的生物利用度，从而增强姜黄素的作用。
BackgroundA disruption of cholesterol homeostasis characterized by the physical-chemical imbalance of cholesterol solubility in bile often results in formation of cholesterol gallstones. Our earlier studies revealed that curcumin (1000 mg/kg) could prevent formation of gallstones. It has been proved that curcumin is poorly absorbed while piperine is a bioavailability-enhancer. Nevertheless, whether curcumin combined with piperine could enhance the effect of curcumin in preventing gallstones is still awaited.MethodC57BL6 mice were fed on a lithogenic diet concomitant with curcumin at 500 or 1000 mg/kg and/or piperine at 20 mg/kg for 4 weeks. The ratio of gallbladder stone formation was recorded and samples of blood, bile, gallbladder, liver and small intestine were also collected. The volume of gallbladder and weight of liver were calculated, and blood and bile samples were analyzed through biochemical methods. Intestinal NPC1L1 and SREBP2 mRNA and protein expression were detected by real-time PCR and Western blot.ResultCombining with piperine can significantly enhance the effect of curcumin, thus preventing the development of gallbladder stones, lowering the saturation of blood lipids and cholesterol in bile, as well as decreasing the expression of NPC1L1 and SREBP2 in both mRNA and protein levels.ConclusionCurcumin can prevent the formation of cholesterol gallstones induced by high fat diet in mice and SREBP2 and NPC1L1 may participate in this process. Piperine can increase curcumin’s bioavailability, thereby enhancing the effect of curcumin.