scholarly journals A mechanism for the hypocholesterolaemic activity of saponins

1986 ◽  
Vol 55 (3) ◽  
pp. 643-649 ◽  
Author(s):  
G. S. Sidhu ◽  
D. G. Oakenfull
Keyword(s):  
Small Intestine ◽  
Bile Acid ◽  
Bile Salt ◽  
Plasma Cholesterol ◽  
Sodium Cholate ◽  
Food Plants ◽  
Faecal Excretion ◽  
Rate Of Absorption ◽  
Nutritional Benefits

1. Saponins are steroid or triterpene glycosides which occur in a number of important food plants, including such staples as soya beans (Glycine max) and chickpeas (Cicer arietinurn). They are known to be hypocholesterolaemic.2. Some saponins form an insoluble complex with cholesterol which prevents its absorption from the small intestine. Others cause an increase in the faecal excretion of bile acids, an indirect route for elimination of cholesterol.3. We have investigated the effects of different saponins on absorption of the bile salt sodium cholate from perfused loops of small intestine, in vivo, in the rat. Purified saponins from soapwort (Suponaria Officinalis), soya beans and quillaia (Quillata suponaria) reduced the rate of absorption of the bile salt; soya-bean and soapwort saponins substantially so but quillaia saponin to a much lesser extent.4. These results were explained by the formation of large mixed micelles by bile acid and saponin molecules in aqueous solution. These aggregates can have molecular weights in excess of 106 daltons, consequently the bile acid molecules incorporated in them are not available for absorption.5. Control of plasma cholesterol and nutrient absorption through dietary saponins could provide substantial health and nutritional benefits in humans.

scholarly journals Broiler chicken body weights, feed intakes, plasma lipid and small-intestinal bile acid concentrations in response to feeding of chitosan and pectin

1997 ◽  
Vol 78 (2) ◽  
pp. 283-291 ◽  
Author(s):  
A. Razdan ◽  
D. Pettersson ◽  
J. Pettersson
Keyword(s):  
Small Intestine ◽  
Bile Acid ◽  
Broiler Chicken ◽  
Plasma Cholesterol ◽  
Control Diet ◽  
Plasma Lipid ◽  
Cholesterol Ratio ◽  
Body Weights

One-day-old broiler chickens were fed on a control diet based on maize and maize starch or diets containing 30g/kg of 89 % deacetylated chitin (chitosan) or low-methoxyl (34 % degree of esterification) pectin. Feeding of the chitosan diet to chickens significantly reduced body weights and feed intakes compared with animals fed on control or pectin diets on days 5 and 11 of the experiment. On day 12, significant reductions in total plasma cholesterol and HDL-cholesterol concentrations were observed among birds fed on the chitosan but not the pectin diet in relation to control-fed animals. A concomitant increase in the plasma HDL-cholesterol:total cholesterol ratio was observed among chitosan-fed chickens. The generally reduced concentrations of primary and total bile acids in the duodenum of birds fed on the fibre-containing diets on day 13 may have been an indication of a delay in the production and/or secretion of bile. Viscosity of the three broiler-chicken diets was measured after suspension in water, acidification and finally neutralization of the suspensions, in an attempt to simulate the effect of changes in pH and dilution of diets occurring in the gizzard and small intestine of chickens. Viscosity of the chitosan diet was significantly elevated after acidification and significantly reduced at neutralization in comparison with the control and pectin-containingdiets suggesting that the hypolipidaemic influence of chitosan observed in the present study may be due to interruption of enterohepatic bile acid circulation rather than increased viscosity in the small intestine of chickens. The low viscosity of the pectin dietin vitrotogether with the absence of a hypocholesterolaemic effect of this diet when fedin vivoprecludes any conclusion regarding the hypocholesterolaemic mechanism of pectin observed in earlier studies.

Interrelationship of Plasma Cholate and Phospholipid Concentrations and Their Resultant Effect on Plasma Cholesterol in Biliary Obstruction

1957 ◽  
Vol 188 (2) ◽  
pp. 337-341 ◽  
Author(s):  
Meyer Friedman ◽  
Sanford Byers
Keyword(s):  
Bile Acid ◽  
Intravenous Injection ◽  
Biliary Obstruction ◽  
Plasma Cholesterol ◽  
Plasma Phospholipid ◽  
Sodium Cholate ◽  
Phospholipid Ratio ◽  
Resultant Effect ◽  
Normal Rat

Elevation of plasma cholate (by intravenous injection of sodium cholate) in both the normal rat and the rat with biliary obstruction was found to lead to an elevation of plasma phospholipid and cholesterol. Experimental elevation of plasma phospholipid (also by injection), however, while leading to an elevation of plasma cholesterol did not elevate the plasma cholate in either the normal or obstructed rat. Furthermore, comparison of the cholesterol-phospholipid ratio obtained in rats by infusion of phosphatide with those observed in rats with biliary obstruction suggests that the plasma phospholipid elevation occurring spontaneously in these latter rats induced the hypercholesteremia observed. In view of these observations, it is suggested the elevation of plasma bile acid occurring in biliary obstruction effects its hypercholesteremic effect by first leading to the elevation of plasma phospholipid. The latter in turn leads to the hypercholesteremia observed.

A Multicompartmental Dynamic Computer-controlled Model Simulating the Stomach and Small Intestine

1995 ◽  
Vol 23 (2) ◽  
pp. 197-209 ◽  
Author(s):  
Mans Minekus ◽  
Phillipe Marteau ◽  
Robert Havenaar ◽  
Jos H.J. Huis in't Veld
Keyword(s):  
Small Intestine ◽  
Bile Salt ◽  
Computer Control ◽  
Gastrointestinal Transit ◽  
Glucose Absorption ◽  
Laboratory Animals ◽  
Healthy Human ◽  
Dynamic Events

A multicompartmental in vitro model has been described, which simulates the dynamic events occurring within the lumen of the gastrointestinal tract of man and monogastric animals. The accuracy of the model for reproducing in vivo data on gastrointestinal transit, pH, bile salt concentrations and the absorption of glucose was tested. The in vivo conditions simulated in the model were based on studies in healthy human volunteers. Mathematical modelling of gastric and ileal delivery with power exponential equations was used for the computer control of meal transit. The model appeared to reproduce accurately the pre-set data on meal transit, pH and bile salt concentrations in the different gastrointestinal compartments. Glucose absorption from the small intestine was almost complete. This model reproduces very closely the dynamic conditions based on the in vivo situation in monogastric animals and man. Therefore, the model can be an important tool in studying the fate of ingested components (for example, food, microorganisms and medicines) during gastrointestinal transit and, consequently, may contribute to the replacement of studies using laboratory animals.

scholarly journals Development of a Covalent Inhibitor of Gut Bacterial Bile Salt Hydrolases

2019 ◽  
Author(s):  
Arijit A. Adhikari ◽  
Tom C. Seegar ◽  
Scott B. Ficarro ◽  
Megan D. McCurry ◽  
Deepti Ramachandran ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Salt ◽  
Bile Acids ◽  
Unmet Need ◽  
Cysteine Residue ◽  
Gut Bacteria ◽  
Bile Salt Hydrolase ◽  
Secondary Bile Acid ◽  
Bsh Activity

AbstractBile salt hydrolase (BSH) enzymes are widely expressed by human gut bacteria and catalyze the gateway reaction leading to secondary bile acid formation. Bile acids regulate key metabolic and immune processes by binding to host receptors. There is an unmet need for a potent tool to inhibit BSHs across all gut bacteria in order to study the effects of bile acids on host physiology. Here, we report the development of a covalent pan-inhibitor of gut bacterial BSH. From a rationally designed candidate library, we identified a lead compound bearing an alpha-fluoromethyl ketone warhead that modifies BSH at the catalytic cysteine residue. Strikingly, this inhibitor abolished BSH activity in conventional mouse feces. Mice gavaged with a single dose of this compound displayed decreased BSH activity and decreased deconjugated bile acid levels in feces. Our studies demonstrate the potential of a covalent BSH inhibitor to modulate bile acid composition in vivo.

Altered Bile Acid Metabolism during Treatment with Phenobarbitone

1973 ◽  
Vol 45 (2) ◽  
pp. 257-262 ◽  
Author(s):  
N. E. Miller ◽  
P. J. Nestel
Keyword(s):  
Bile Acid ◽  
Acid Metabolism ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Specific Radioactivity ◽  
Density Lipoprotein ◽  
Bile Acid Metabolism ◽  
Faecal Excretion ◽  
Healthy Humans ◽  
Early Rise

1. The effects of phenobarbitone on cholesterol and bile acid metabolism have been examined in healthy humans. 2. In three of four subjects the faecal excretion of bile acids was increased by phenobarbitone. This was associated with an increased pool size and turnover of cholic acid. Cholesterol excretion was not clearly affected. The fourth subject who did not respond was also exceptional in not showing an increase in the plasma clearance of antipyrine. 3. The three responsive subjects also developed significant increases in plasma cholesterol and triglyceride concentrations. These findings were associated with an early rise in very-low-density lipoprotein and a fall in plasma cholesterol specific radioactivity in one patient, changes compatible with increased cholesterol synthesis.

scholarly journals Pathology of Infestation of the Rat With Nippostrongylus Muris (Yokogawa) IV. The Absorption of Glucose and Histidine

1960 ◽  
Vol 13 (2) ◽  
pp. 180 ◽  
Author(s):  
LEA Symons
Keyword(s):  
Small Intestine ◽  
Gastric Emptying ◽  
Direct Relationship ◽  
The Other ◽  
Perfusion Technique ◽  
Intubation Technique ◽  
Entire Small Intestine ◽  
Other Hand ◽  
Rate Of Absorption

The rate of absorption of D-glucose and L-histidine from the entire small intestine of the rat when measured by an intubation technique was not affected by infestation with the nematode Nippostrongylu8 muris. On the other hand, absorption of D-glucose from the infested jejunum when measured in vivo by a perfusion technique was severely reduced. The rate of gastric emptying was not affected by the infestation. There was a direct relationship between gastric emptying and the rate of absorption of glucose.

scholarly journals A gut-restricted lithocholic acid analog as an inhibitor of gut bacterial bile salt hydrolases

2021 ◽  
Author(s):  
Arijit A. Adhikari ◽  
Deepti Ramachandran ◽  
Snehal N. Chaudhari ◽  
Chelsea E. Powell ◽  
Megan D. McCurry ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Salt ◽  
Bile Acids ◽  
Mammalian Cells ◽  
Lithocholic Acid ◽  
Bile Salt Hydrolase ◽  
Host Physiology ◽  
Secondary Bile Acids ◽  
Bsh Activity

AbstractBile acids play crucial roles in host physiology by acting as both detergents that aid in digestion and as signaling molecules that bind to host receptors. Gut bacterial bile salt hydrolase (BSH) enzymes perform the gateway reaction leading to the conversion of host-produced primary bile acids into bacterially modified secondary bile acids. Small molecule probes that target BSHs will help elucidate the causal roles of these metabolites in host physiology. We previously reported the development of a covalent BSH inhibitor with low gut permeability. Here, we build on our previous findings and describe the development of a second-generation gut-restricted BSH inhibitor with enhanced potency, reduced off-target effects, and durable in vivo efficacy. SAR studies focused on the bile acid core identified a compound, AAA-10, containing a C3-sulfonated lithocholic acid scaffold and an alpha-fluoromethyl ketone warhead as a potent pan-BSH inhibitor. This compound inhibits BSH activity in conventional mouse fecal slurries, bacterial cultures, and purified BSH proteins and displays reduced toxicity against mammalian cells compared to first generation compounds. Oral administration of AAA-10 to wild-type mice for 5 days resulted in a decrease in the abundance of the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA) in the mouse GI tract with low systemic exposure of AAA-10, demonstrating that AAA-10 is an effective tool for inhibiting BSH activity and modulating bile acid pool composition in vivo.

scholarly journals Hypocholesterolaemic effect of dietary inclusion of two putative probiotic bile salt hydrolase-producingLactobacillus plantarumstrains in Sprague–Dawley rats

2010 ◽  
Vol 105 (4) ◽  
pp. 561-573 ◽  
Author(s):  
Rajesh Kumar ◽  
Sunita Grover ◽  
Virender Kumar Batish
Keyword(s):  
Bile Salt ◽  
Plasma Cholesterol ◽  
Dietary Treatment ◽  
Normal Diet ◽  
Bile Salt Hydrolase ◽  
Sprague Dawley ◽  
Faecal Excretion ◽  
Treatment Groups ◽  
Sprague Dawley Rats ◽  
Probiotic Treatment

The purpose of the present study was to evaluate the anti-hypercholesterolaemic effects of two putative probiotic bile salt hydrolase (Bsh)-producingLactobacillusplantarumstrains, i.e. Lp91 and Lp21, in rats.L. plantarumLp91 exhibited excellent tolerance to low pH and high bile salt concentrations as well as showed potential Bsh activity, cholesterol assimilation and cholesterol co-precipitation ability along withL. plantarumLp21 and NCDO82 strains. Furthermore, the potential effect ofL. plantarumLp91 on plasma cholesterol level was evaluated in Sprague–Dawley rats. Five treatment groups of rats (n6) were fed experimental diets: normal diet, hypercholesterolaemic diet (HD), HD plusL. plantarumLp91 (HD91) at ≥ 1·0 × 108colony-forming units (cfu)/g, HD plus microencapsulatedL. plantarumLp91 (HDCap91) at ≥ 1·0 × 108 cfu/g and HD plusL. plantarumLp21 (HD21) at ≥ 1·0 × 108 cfu/g for 3 weeks. Feed intake and feed efficiency differed significantly among the five groups. After 21 d of dietary treatment, comparative analysis revealed 23·26, 15·71 and 15·01 % reduction in total cholesterol, 21·09, 18·77 and 18·17 % reduction in TAG, 38·13, 23·22 and 21·42 % reduction in LDL-cholesterol, and the corresponding HDL-cholesterol values increased at the rate of 18·94, 10·30 and 7·78 % in treated groups HD91, HDCap91 and HD21, respectively. Faecal excretion of cholic acid and faecal lactobacilli counts were significantly higher in the probiotic treatment groups than in the control groups. In conclusion, these results suggest that the indigenousL. plantarumLp91 strain has the potential to be explored as a probiotic in the management of hypercholesterolaemia.

scholarly journals Acute in vivo studies on glucose absorption from the small intestine of lambs, sheep and rats

1971 ◽  
Vol 25 (1) ◽  
pp. 57-76 ◽  
Author(s):  
R. G. White ◽  
V. J. Williams ◽  
R. J. H. Morris
Keyword(s):  
Body Weight ◽  
Small Intestine ◽  
Absorptive Capacity ◽  
Glucose Absorption ◽  
In Vivo Studies ◽  
Adult Sheep ◽  
Young Rats ◽  
Unit Body Weight ◽  
Rate Of Absorption

1. Rates of disappearance of glucose from ligated loops of small intestine in lambs, adult sheep and young rats were studied. The concentration of glucose in the lumen decreased exponentially with time, suggesting that within a range of concentrations of 166–277 m-moles/l glucose was absorbed mainly by passive diffusion.2. The rate of absorption of glucose from a 166 mM-solution based on either zero or first order kinetics and expressed as m-moles/m small intestine per h decreased along the intestine from the duodenum to the ileum in lambs and rats. The decrease was slight in adult sheep.3. The total absorptive capacity of the small intestine of adult grazing sheep for glucose from 166 mM-solutions (06 m-moles/kg body-weight per h) was approximately 25% of that for lambs less than 1 week of age.4. Young rats had a greater absorptive capacity of the small intestine (12.9m-moles/kg body-weight per h) than adult sheep of about 40 kg body-weight (0.6 m-moles/kg body-weight per h) and this largely reflected a longer small intestine per unit body-weight.5. The absorptive capacity of lambs for glucose was greater when the level of voluntary lactose intake was increased before an experiment. The absorptive capacity of the ileum of adult sheep given wheat was greater than that of grazing adult sheep.6. Developmental changes in glucose absorption are discussed in relation to normal changes in diet and to changes in the morphology of the small intestine with age.

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