Isocoumarin-based inhibitors of pancreatic cholesterol esterase

Heynekamp, Justin J.; Hunsaker, Lucy A.; Jagt, Thomas A. Vander; Royer, Robert E.; Deck, Lorraine M.; Jagt, David L. Vander

doi:10.1016/j.bmc.2008.03.016

“…Flavonoids have been reported to irreversibly bind with the cholesterol esterase enzyme in its active fatty acid pocket at Serine 194. It was also suggested that the flavonoids act as suicide substrates ahead of cholesterol esters 23 .…”

Section: Resultsmentioning

confidence: 99%

Untitled

2011

IJPSR

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The present study was to evaluate the in vitro cholesterol esterase enzyme inhibitory and in vitro antioxidant activity of the methanol extract of the leaves of Camellia sinensis (L.). Phytochemical screening of the extract shows the presence of flavonoids, phenolics and terpenoids. The extract shows ability to inhibit the enzyme with IC 50 (82.46±0.74µg/ml) where as that of standard, Orlistat (24.15±0.59µg/ml). Antioxidant and free radical scavenging activity were also assessed by using the methods, IC 50 values for Nitric oxide radical scavenging activity (396.83±0.83µg/ml), whereas for standard curcumin (260.38±0.66µg/ml), hydroxyl radical scavenging activity (47.04±2.26µg/ml) and for quercetin (70.99±1.31µg/ml). Moreover, the extract was found to scavenge the superoxide with 50% inhibition at 308.17±23.25µg/ml and standard ascorbic acid at 225.08±2.44µg/ml, IC 50 for ferrous chelating ability assay (44.12±4.63µg/ml) and of ascorbic acid (47.25±.89µg/ml). Total content of flavonoids present in 1mg of extract was 19.8±0.11 µg quercetin equivalents/mg. Results indicated that the extract shows potential bioactive compounds which might have a beneficial impact on diseases related to cholesterol synthesis and showed potential antioxidant and free radical scavenging activities. INTRODUCTION: Dietary cholesterol comprised of free and esterified cholesterol. In diets rich in meats, significant percent of cholesterol is esterified. Hydrolysis of cholesteryl ester in the lumen is catalyzed by cholesterol esterase (CEase).Cholesterol esterase (CEase) also is a lipolytic enzyme with wide substrate specificity capable of hydrolysing cholesteryl esters, triacylglycerol, phospholipids and lysophospholipids. It is synthesized primarily by the pancreas and is found as a component of pancreatic juice.This enzyme is also found in the milk of numerous species. Milk CEase is postulated to substitute for the pancreatic enzyme in the neonatal gastrointestinal tract before maturation of the pancreas 1 . Pancreatic cholesterol esterase is also known as bile salt-activated lipase, nonspecific lipase, phospholipase A 1 lysophospholipase, bile salt-dependent lipase, bile salt stimulated lipase, carboxyl ester lipase, and carboxyl ester hydrolase 2 .A number of studies have suggested a possible role for CEase in the absorption of free cholesterol at the brush border membrane of the small intestine 3 . Cholesterol and its esters are the major risk factors for the development of various cardiovascular diseases and are known to be one of the leading causes of death in developing and developed countries. Free radical is an atom with at least one unpaired electron in the outer

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“…Flavonoids have been reported to irreversibly bind with the cholesterol esterase enzyme in its active fatty acid pocket at Serine 194. It was also suggested that the flavonoids act as suicide substrates ahead of cholesterol esters 23 . The inhibitory effect of the extract against bovine pancreatic cholesterol esterase was performed, which showed good activity and the same was comparable with that of the standard used, Orlistat.…”

Section: Resultsmentioning

confidence: 99%

Untitled

2011

IJPSR

0

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The present study was to evaluate the in vitro cholesterol esterase enzyme inhibitory and in vitro antioxidant activity of the methanol extract of the leaves of Camellia sinensis (L.). Phytochemical screening of the extract shows the presence of flavonoids, phenolics and terpenoids. The extract shows ability to inhibit the enzyme with IC 50 (82.46±0.74µg/ml) whereas that of standard, Orlistat (24.15±0.59µg/ml). Antioxidant and free radical scavenging activity were also assessed by using the methods, IC 50 values for Nitric oxide radical scavenging activity (396.83±0.83µg/ml), whereas for standard curcumin (260.38±0.66µg/ml), hydroxyl radical scavenging activity (47.04±2.26µg/ml) and for quercetin (70.99±1.31µg/ml). Moreover, the extract was found to scavenge the superoxide with 50% inhibition at 308.17±23.25µg/ml and standard ascorbic acid at 225.08±2.44µg/ml, IC 50 for ferrous chelating ability assay (44.12±4.63µg/ml) and of ascorbic acid (47.25±.89µg/ml). Total content of flavonoids present in 1mg of extract was 19.8±0.11 µg quercetin equivalents/mg. Results indicated that the extract shows potential bioactive compounds which might have a beneficial impact on diseases related to cholesterol synthesis and showed potential antioxidant and free radical scavenging activities. INTRODUCTION:Dietary cholesterol comprised of free and esterified cholesterol. In diets rich in meats, significant percent of cholesterol is esterified. Hydrolysis of cholesteryl ester in the lumen is catalyzed by cholesterol esterase (CEase).

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“…The well-established link between plasma cholesterol levels and coronary artery disease and the contribution of elevated plasma cholesterol, specifically Low Density Lipoprotein (LDL)-cholesterol, to other diseases including cancer, obesity and diabetes, have made control of plasma cholesterol a major health aim [5].…”

Section: Introductionmentioning

confidence: 99%

HMG CoA reductase inhibition by Simvastatin gets rat <i>β</i>-Myosin heavy chain disappeared: A statin paradox

Trapani¹,

Segatto²,

Jóźwiak³

et al. 2013

OJMIP

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ABSTRACT3-hydroxy-3methylglutaryl Coenzyme A reductase, the rate limiting enzyme of mevalonate pathway, generates, in addition to cholesterol, a range of products involved in several biological functions: oligoprenyl groups, dolichol and ubiquinone. The latter, in particular, participates in electron transport chain and, in turn, in tissue energy supply. The enzyme is inhibited by statins that, besides lowering cholesterolemia, seem to impair human energy-dependent myocardial functions (e.g. stroke volume, cardiac output, and contractile index). The modulation of heart contractile properties could be explained by the decrease of ventricle ubiquinone content and/or by putative changes in proportion of the different myosin heavy chain isoforms. Since we previously demonstrated that chronic statin treatment modifies myosin heavy chain isoform pattern in skeletal muscle impairing its functional properties, this work was aimed at investigating the effects of statin chronic treatment on both ventricle ubiquinone content and myosin heavy chain isoforms. Our results showed that simvastatin treatment leads to a reduced amount of rat ventricle ubiquinone and to β myosin heavy chain disappearance. Thus, statins which are prescribed to prevent cardiovascular disease, might induce cardiac metabolic and structural modifications whose functional implications on contractility are still to be established and carefully considered.

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Isocoumarin-based inhibitors of pancreatic cholesterol esterase

Cited by 61 publications

References 20 publications

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HMG CoA reductase inhibition by Simvastatin gets rat <i>β</i>-Myosin heavy chain disappeared: A statin paradox

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Isocoumarin-based inhibitors of pancreatic cholesterol esterase

Cited by 61 publications

References 20 publications

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HMG CoA reductase inhibition by Simvastatin gets rat &lt;i&gt;β&lt;/i&gt;-Myosin heavy chain disappeared: A statin paradox

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HMG CoA reductase inhibition by Simvastatin gets rat <i>β</i>-Myosin heavy chain disappeared: A statin paradox