Abstract
Phytosterols, besides hypocholesterolemic effect, present anti-inflammatory properties. Little information is available about their efficacy in Inflammatory Bowel Disease (IBD). Therefore, we have evaluated the effect of a mixture of phytosterols on prevention/induction/remission in a murine experimental model of colitis. Phytosterols were administered x os before, during and after colitis induction with Dextran Sodium Sulfate (DSS) in mice. Disease Activity Index (DAI), colon length, histopathology score, 18F-FDG microPET, oxidative stress in the intestinal tissue (ileum and colon) and gallbladder ileum and colon spontaneous and carbachol (CCh) induced motility, plasma lipids and plasma, liver and biliary bile acids (BA) were evaluated. A similar longitudinal study was performed in a DSS colitis control group. Mice treated with DSS developed severe colitis as shown by DAI, colon length, histopathology score, 18F-FDG microPET, oxidative stress. Both spontaneous and induced ileal and colonic motility were severely disturbed. The same was observed with gallbladder. DSS colitis resulted in an increase in plasma cholesterol, and a modification of the BA pattern. Phytosterols feeding did not prevent colitis onset but significantly reduced the severity of the disease and improved clinical and histological remission. It had strong antioxidant effects, almost restored colon, ileal and gallbladder motility. Plasmatic levels of cholesterol were also reduced. DSS induced a modification in the BA pattern consistent with an increase in the intestinal BA deconjugating bacteria, prevented by phytosterols. Phytosterols seem a potential nutraceutical tool for gastrointestinal inflammatory diseases, combining metabolic systematic and local anti-inflammatory effects.
Highlights
There has been a raising an interest towards essential oils and lipid-soluble bioactive compounds from various natural sources among scientists.Phytosterols and phytostanols are plant derived sterols, structurally related to cholesterol
In contrast to C57BL/6 mice where a short 5-day exposure of Dextran Sodium Sulfate (DSS) is sufficient to induce progressive chronic colitis, at the same schedule, BALB/c mice develop acute colitis, which resolves after DSS removal [24]
The results demonstrate that DSS induced colitis is associated with an increase of secondary bile acids, due to the increased bacterial 7a-dehydroxylation, resulting from inflammation, which can be partly prevented by phytosterols
Summary
Phytosterols and phytostanols are plant derived sterols, structurally related to cholesterol. Saturated forms of plant sterols (phytostanols) are less represented in nature than the unsaturated forms (terols) [2]. Woods and vegetables are the main sources for pharmaceutical phytosterols [3]. Phytosterols are natural components of human diets, and they are found, mostly, in vegetable oils, cereals, fruits and vegetables, while common dietary sources of phytostanols are corn, wheat, rye, and rice [4]. B-sitosterol, the main sterol of several plant species, has been shown to exert anti-inflammatory, anticancer, antispasmodic, antioxidant, and antidiabetic activities [5] [6] [7] [8]. The exact molecular mechanisms responsible for cholesterol-lowering activity of plant sterols/
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