Piperine prevents cholesterol gallstones formation in mice
Piperine prevents cholesterol gallstones formation in mice
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胡椒碱可预防小鼠胆固醇胆结石的形成
DOI：
10.1016/j.ejphar.2015.01.038
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发表时间：
2015-03-15
影响因子：
5
通讯作者：
Chen, Nai-Hong
中科院分区：
文献类型：
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作者：
Song, Xiu-Yun;Xu, Shuang;Chen, Nai-Hong
胆汁胆固醇可能有助于胆固醇结石的形成，调节这些水平可能是胆结石疾病的有用治疗策略。精氨酸（PA）是一种潜在的降胆固醇药物。本研究旨在探讨PA对高胆固醇致石饲料诱导的小鼠胆固醇结石形成的预防作用及其机制。C57 BL/6近交系小鼠分别饲喂致石饲料或普通饲料10周，给予或不给予PA（15、30和60 mg/kg）或熊去氧胆酸（UDCA，60 mg/kg）。分析胆汁中的胆固醇、磷脂和晶体，血清中的脂质，肝脏的病理变化和蛋白质表达。结果表明，PA能降低胆汁中胆固醇含量和结晶，降低血清中总胆固醇（TC）、甘油三酯（TG），升高高密度脂蛋白/低密度脂蛋白（HDL/LDL）水平。此外，PA治疗减少肝脏脂质过氧化和保护肝细胞免受肝损伤，通过降低丙二醛（MDA）和增加超氧化物歧化酶（SOD）。此外，PA还可抑制肝脏ATP结合盒转运体G5/8（ABCG 5/8）和肝脏X受体（LXR）的表达，并减少胆固醇从肝细胞向胆囊的转运。这可能是PA预防胆固醇结石形成的机制之一。PA作为预防胆固醇结石的潜在药物值得进一步研究。(C)2015 Elsevier By. All rights reserved.
Biliary cholesterol may contribute to the formation of cholesterol gallstones, and regulation of these levels could be a useful therapeutic strategy for gallstones disease. Piperine (PA) is a potential cholesterol lowering agent. In this study, we assessed the effect and mechanism of PA in preventing cholesterol gallstones formation induced by feeding lithogenic diet containing high cholesterol levels to mice. C57BL/6 inbred mice were fed lithogenic or chow diets for 10 weeks, with or without PA (15, 30 and 60mg/kg) or ursodeoxycholic acid (UDCA, 60mg/kg) administration. Cholesterol, phospholipids and crystals in bile, the lipid in serum, pathological changes and proteins expression in liver were analyzed. The results showed that PA could decrease the cholesterol potency and crystals in bile, reduce total cholesterol (TC), triglycerides (TG) and increase high-density lipoprotein/low-density lipoprotein (HDL/LDL) levels in serum. Furthermore, PA treatment reduced liver lipid peroxidation and protected hepatobiliary cells from liver injury by decreasing malondialdehyde (MDA) and increasing superoxide dismutase (SOD). In addition, PA inhibited the expression of ATP-binding cassette transporters G5/8 (ABCG5/8) and liver X receptor (LXR) in liver, and reduced cholesterol transport from the hepatocytes to the gallbladder. It may be the mechanism of PA in preventing cholesterol gallstones formation. PA as a potential drug for prevention cholesterol gallstones merits further investigation. (C) 2015 Elsevier By. All rights reserved.