Combination of curcumin and piperine prevents formation of gallstones in C57BL6 mice fed on lithogenic diet: whether NPC1L1/SREBP2 participates in this process?
BACKGROUND
A 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.


METHODS
C57BL6 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.


RESULTS
Combining 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.


CONCLUSIONS
Curcumin 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.
Biliary & Vascular surgery, Shengjing Hospital of China Medical University, Shenyang City, 110004, PR China. cmuliyongnan@126.com.
Yongnan
Y
Li
Biliary & Vascular surgery, Shengjing Hospital of China Medical University, Shenyang City, 110004, PR China. limin1771@163.com.
Min
M
Li
Biliary & Vascular surgery, Shengjing Hospital of China Medical University, Shenyang City, 110004, PR China. wushuodong@aliyun.com.
Shuodong
S
Wu
Biliary & Vascular surgery, Shengjing Hospital of China Medical University, Shenyang City, 110004, PR China. surgeon_ty@aliyun.com.
Yu
Y
Tian
D000470:Alkaloids / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000924:Anticholesteremic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D052117:Benzodioxoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001682:Biological Availability; D002791:Cholesterol, Dietary / Q000009:adverse effects; D003474:Curcumin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004032:Diet / Q000009:adverse effects; D004338:Drug Combinations; D004357:Drug Synergism; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D042882:Gallstones / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015870:Gene Expression; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010880:Piperidines / Q000493:pharmacokinetics / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000493:pharmacokinetics / Q000494:pharmacology*; D020011:Protective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
D000470:Alkaloids; D000924:Anticholesteremic Agents; D052117:Benzodioxoles; D002791:Cholesterol, Dietary; D004338:Drug Combinations; D026901:Membrane Transport Proteins; C482445:Npc1l1 protein, mouse; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D020011:Protective Agents; D012333:RNA, Messenger; C497391:Srebf2 protein, mouse; D051782:Sterol Regulatory Element Binding Protein 2; D003474:Curcumin; C008922:piperine