curcumin and Gallstones

Dietary hypocholesterolemic spices-curcumin (active compound of turmeric (Curcuma longa)) and capsaicin (active compound of red pepper (Capsicum annuum)), the active principles of spices-turmeric (Curcuma longa) and red pepper (Capsicum annuum), fenugreek (Trigonella foenum-graecum) seeds, garlic (Allium sativum), and onion (Allium cepa) are documented to have anti-cholelithogenic property in animal model. These spices prevent the induction of cholesterol gallstones by lithogenic high cholesterol diet and also regress the pre-established cholesterol gallstones, by virtue of their hypolipidemic potential. The antilithogenic influence of these spices is primarily attributable to their hypocholesterolemic effect. Increased cholesterol saturation index, cholesterol:phospholipid ratio and cholesterol:bile acid ratio in the bile caused by the lithogenic diet was countered by these spices. The antilithogenicity of these hypocholesterolemic spices was considered to be due also to their influence on biliary proteins that have pro-nucleating activity and anti-nucleating activity. Investigations on the involvement of biliary proteins in cholesterol crystal nucleation revealed that in an in vitro bile model, low molecular weight biliary proteins of the lithogenic diet fed animals have a pro-nucleating activity. On the contrary, low molecular weight biliary proteins of the animals fed hypocholesterolemic spices along with lithogenic diet showed a potent anti-nucleating activity.

Topics: Animals; Anticholesteremic Agents; Bile Acids and Salts; Capsaicin; Capsicum; Curcuma; Curcumin; Diet; Disease Models, Animal; Gallstones; Garlic; Humans; Onions; Plant Extracts; Spices; Trigonella

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.. 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.. 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.. 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.

Topics: Alkaloids; Animals; Anticholesteremic Agents; Benzodioxoles; Bile; Biological Availability; Cholesterol, Dietary; Curcumin; Diet; Drug Combinations; Drug Synergism; Gallbladder; Gallstones; Gene Expression; Intestinal Mucosa; Intestines; Liver; Male; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Piperidines; Polyunsaturated Alkamides; Protective Agents; RNA, Messenger; Sterol Regulatory Element Binding Protein 2

Spice bioactive compounds, capsaicin and curcumin, were both individually and in combination examined for antilithogenic potential during experimental induction of cholesterol gallstones in mice. Cholesterol gallstones were induced by feeding mice a high-cholesterol (0.5%) diet for 10 weeks. Groups of mice were maintained on a lithogenic diet that was supplemented with 0.015% capsaicin/0.2% curcumin/0.015% capsaicin + 0.2% curcumin. The lithogenic diet that contained capsaicin, curcumin, or their combination reduced the incidence of cholesterol gallstones by 50%, 66%, and 56%, respectively, compared with lithogenic control. This was accompanied by reduced biliary cholesterol and a marginal increase in phospholipid in these spice-fed groups. Increased cholesterol saturation index and cholesterol : phospholipid ratio in the bile caused by the lithogenic diet was countered by the dietary spice compounds. The antilithogenic influence of spice compounds was attributable to the cholesterol-lowering effect of these dietary spices in blood and liver, as well as a moderate increase in phospholipids. Decreased activities of hepatic glutathione reductase and glutathione-S-transferase caused by the lithogenic diet were countered by the combination of capsaicin and curcumin. The increased lipid peroxidation and the decreased concentration of ascorbic acid in the liver that was caused by the lithogenic diet was countered by the dietary spice compounds, individually or in combination. Thus, while the capsaicin and curcumin combination did not have an additive influence in reducing the incidence of cholesterol gallstones in mice, their combination nevertheless was more beneficial in enhancing the activity of hepatic antioxidant enzyme ─ glutathione reductase in the lithogenic situation. The antioxidant effects of dietary spice compounds are consistent with the observed reduction in cholesterol gallstones formed under lithogenic condition.

Topics: Animals; Antioxidants; Ascorbic Acid; Capsaicin; Cholesterol; Curcumin; Diet; Disease Models, Animal; Gallstones; Glutathione Reductase; Glutathione Transferase; Lipid Peroxidation; Liver; Male; Mice