Functional Effects of Prebiotic Fructans in Colon Cancer and Calcium Metabolism in Animal Models.

Inulin-type fructans are polymers of fructose molecules and are known for their capacity to enhance absorption of calcium and magnesium, to modulate gut microbiota and energy metabolism, and to improve glycemia. We evaluated and compared the effects of Chicory inulin "Synergy 1®" and inulin from Mexican agave "Metlin®" in two experimental models of colon cancer and bone calcium metabolism in mice and rats. Inulins inhibited the development of dextran sulfate sodium-induced colitis and colon cancer in mice; these fructans reduced the concentration of tumor necrosis factor alpha and prevented the formation of intestinal polyps, villous atrophy, and lymphoid hyperplasia. On the other hand, inulin treatments significantly increased bone densitometry (femur and vertebra) in ovariectomized rats without altering the concentration of many serum biochemical parameters and urinary parameters. Histopathology results were compared between different experimental groups. There were no apparent histological changes in rats treated with inulins and a mixture of inulins-isoflavones. Our results showed that inulin-type fructans have health-promoting properties related to enhanced calcium absorption, potential anticancer properties, and anti-inflammatory effects. The use of inulin as a prebiotic can improve health and prevent development of chronic diseases such as cancer and osteoporosis.

The Hypocholesterolemic Effects of Eryngium carlinae F. Delaroche Are Mediated by the Involvement of the Intestinal Transporters ABCG5 and ABCG8.

Hypercholesterolemia is a metabolic disorder characterized by a high concentration of cholesterol in the blood. Eryngium carlinae is a medicinal plant used to treat lipid diseases. The goal of this work was to evaluate, in a model of hypercholesterolemia in mice, the hypocholesterolemic effect of a hydroalcoholic extract of E. carlinae and its main metabolite, D-mannitol. Biochemical analyses of serum lipids and hepatic enzymes were performed by photocolorimetry. We performed histopathological studies of the liver and the expression of the intestinal cholesterol transporters Abcg5 and Abcg8 was determined by standard western blot method. Our results showed that hydroalcoholic extract at doses of 100 mg/kg and D-mannitol at doses of 10 mg/kg reduced the concentration of both total cholesterol and non-HDL cholesterol, without altering the concentration of HDL cholesterol and without damage to hepatocytes. Treatment with the extract increased Abcg8 intestinal transporter expression, while D-mannitol decreased the expression of the two Abcg5/Abcg8 transporters, compared with the hypercholesterolemic group. Considering that Abcg5/Abcg8 transporters perform cholesterol efflux, our results demonstrate that the lipid-lowering effect of the hydroalcoholic extract may be associated with the increase of Abcg8 expression, but the hypocholesterolemic effect of D-mannitol is independent of overexpression of these intestinal transporters and probably they have another mechanism of action.

Future therapeutic targets for the treatment and prevention of cholesterol gallstones.

The formation of cholesterol gallstones involves very complex imbalances, such as alterations in the secretion of biliary lipids (which involves the ABCG5, ABCG8, ABCB4 and ABCB11 transporters), biochemical and immunological reactions in the gallbladder that produce biliary sludge (mucins), physicochemical changes in the structure of cholesterol (crystallization), alterations in gallbladder motility, changes in the intestinal absorption of cholesterol (ABCG5/8 transporters and Niemann-Pick C1L1 protein) and alterations in small intestine motility. Some of these proteins have been studied at the clinical and experimental levels, but more research is required. In this review, we discuss the results of studies on some molecules involved in the pathophysiology of gallstones that may be future therapeutic targets to prevent the development of this disease, and possible sites for treatment based mainly on the absorption of intestinal cholesterol (Niemann-Pick C1L1 and ABCG5/8 proteins).

Intestinal and hepatic Niemann-Pick C1L1 proteins: future therapeutic targets for cholesterol gallstones disease?

The formation of cholesterol gallstones is a very complex and polygenic disorder that involves an alteration of the secretion of bile lipids, cholesterol crystallization, important immunological reactions in the gallbladder tissue, formation of biliary sludge composed of mucin, and inadequate gallbladder motility. The search for a therapeutic target is oriented towards decreasing bile secretion and intestinal absorption of cholesterol, in which Niemann-Pick C1L1 (NPC1L1) proteins play an important role. In basic and clinical studies, regulating the expression of these proteins can reduce intestinal, liver, plasma and bile cholesterol levels, a therapeutic effect that would be useful not only for treating the disease, but to prevent it, given the large quantity of risk factors. We discuss these effects in this review and propose NPC1L1 proteins as future therapeutic targets of cholesterol gallstones disease.

Two glucosinolates and their effects related to the prevention of cholesterol gallstones: a review / Dos glucosinolatos y sus efectos asociados con la prevención de cálculos biliares de colesterol: una revisión

Two glucosinolates (glucoraphasatin and glucoraphanin) and their degradation products (raphasatin and sulforaphane) are secondary metabolites which have shown antioxidant properties and inhibitory properties against the hepatic cholesterol; these effects are very important for the prevention of cholesterol gallstones because in their pathophysiology there is an imbalance in the transport and secretion of cholesterol. These effects produce oxygen reactive species formation, which damages the hepatic and biliary tissues. Cholesterol gallstones are a public health problem; their pharmacological treatment is very limited and the invasive surgical treatment for symptomatic gallstones is the cholecystectomy. Current research focuses on the search for preventive treatments, as there are many risk factors associated with the development of gallstones; therefore, a natural therapeutic alternative may be the use of these glucosinolates and their degradation products.

Dos glucosinolatos (glucorafasatina y glucorafanina) y sus productos de degradación (rafasatina y sulforafano) son metabolitos secundarios que han demostrado propiedades antioxidantes y propiedades inhibidoras contra el colesterol hepático; estos efectos son muy importantes para la prevención de cálculos biliares de colesterol porque en su fisiopatología existe un desajuste en el transporte y secreción del colesterol. Estos efectos producen la formación de especies reactivas de oxígeno, que dañan los tejidos hepático y biliar. Los cálculos biliares de colesterol son un problema de salud pública, su terapia farmacológica es muy limitada y el tratamiento quirúrgico invasivo para cálculos biliares sintomáticos es la colecistectomía. Las investigaciones actuales están orientadas a la búsqueda de tratamientos preventivos, porque hay muchos factores de riesgo asociados al desarrollo de cálculos biliares; por lo tanto, una alternativa terapéutica natural podría ser el uso de estos glucosinolatos, así como sus productos de degradación.

Raphanus sativus L. var niger as a source of phytochemicals for the prevention of cholesterol gallstones.

Raphanus sativus L. var niger (black radish) is a plant of the cruciferous family with important ethnobotanical uses for the treatment of gallstones in Mexican traditional medicine. It has been established that the juice of black radish decreases cholesterol levels in plasma and dissolves gallstones in mice. Glucosinolates, the main secondary metabolites of black radish, can hydrolyze into its respective isothiocyanates and have already demonstrated antioxidant properties as well as their ability to diminish hepatic cholesterol levels; such therapeutic effects can prevent the formation of cholesterol gallstones. This disease is considered a current problem of public health. In the present review, we analyze and discuss the therapeutic effects of the main glucosinolates of black radish, as well as the effects that this plant has on cholesterol gallstones disease.

Antilithiasic and hypolipidaemic effects of Raphanus sativus L. var. niger on mice fed with a lithogenic diet.

In Mexico, Raphanus sativus L. var. niger (black radish) has uses for the treatment of gallstones and for decreasing lipids serum levels. We evaluate the effect of juice squeezed from black radish root in cholesterol gallstones and serum lipids of mice. The toxicity of juice was analyzed according to the OECD guidelines. We used female C57BL/6 mice fed with a lithogenic diet. We performed histopathological studies of gallbladder and liver, and measured concentrations of cholesterol, HDL cholesterol and triglycerides. The juice can be considered bioactive and non-toxic; the lithogenic diet significantly induced cholesterol gallstones; increased cholesterol and triglycerides levels, and decreased HDL levels; gallbladder wall thickness increased markedly, showing epithelial hyperplasia and increased liver weight. After treatment with juice for 6 days, cholesterol gallstones were eradicated significantly in the gallbladder of mice; cholesterol and triglycerides levels decreased too, and there was also an increase in levels of HDL (P < 0.05). Gallbladder tissue continued to show epithelial hyperplasia and granulocyte infiltration; liver tissue showed vacuolar degeneration. The juice of black radish root has properties for treatment of cholesterol gallstones and for decreasing serum lipids levels; therefore, we confirm in a preclinical study the utility that people give it in traditional medicine.