The Effect Of Cholesterol Esterase Biology Essay

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study examined the effect of cholesterol esterase on the degradation of commercial poly and poly. Unstrained PEU and PCU films were incubated in CE solution or a buffer control. The study used a concentration of cholesterol esterase that was considerably higher than the estimated physiological level in order to accelerate degradation. However, characterization of treated polyurethane films with SEM, attenuated total reflectance Fourier transform infrared (ATR-FTIR) and GPC analysis revealed only a small loss in surface soft segment content. Comparison with implanted PEU and PCU films led to the conclusion that any effect of enzymatic hydrolysis was confined to the immediate surface, and the magnitude of the effect was too small to contribute significantly to in vivo degradation. The study confirmed that oxidation, rather than enzymatic hydrolysis, is the primary mechanism responsible for the observed biodegradation of PEU and PCU. The oxidative H2O2/CoCl2 treatment continues to accurately predict the long-term biostability of polyurethanes.

Rosenblat et al.,

demonstrated antiatherogenic properties of extra virgin olive oil (EVOO) enriched with green tea polyphenols (GTPPs) in comparison to EVOO, were studied in the atherosclerotic apolipoprotein-E-deficient (E0) mice. E0 mice (eight mice in each group) consumed EVOO or EVOO-GTPP by gavage feeding. The placebo group received only water. At the end of the study, blood samples, peritoneal macrophages and aortas were collected. Consumption of EVOO or EVOO-GTPP resulted in a minimal increase in serum total and high-density lipoprotein (HDL) cholesterol levels (by 12%) and in serum paraoxonase 1 activity (by 6% and 10%). EVOO-GTPP (but not EVOO) decreased the susceptibility of the mouse serum to AAPH-induced lipid peroxidation (by 18%), as compared to the placebo-treated mice. The major effect of both EVOO and EVOO-GTPP consumption was on HDL-mediated macrophage cholesterol efflux. Consumption of EVOO stimulated cholesterol efflux rate from mouse peritoneal macrophages (MPMs) by 42%, while EVOO-GTPP increased it by as much as 139%, as compared to MPMs from placebo-treated mice. Finally, the atherosclerotic lesion size of mice was significantly reduced by 11% or 20%, after consumption of EVOO or EVOO-GTPP, respectively.

We thus conclude that EVOO possesses beneficial antiatherogenic effects, and its enrichment with GTPPs further improved these effects, leading to the attenuation of atherosclerosis development.

Deepak Bhatnagar.et.al:

Despite intense debate on the benefits of cholesterol lowering, the use of lipid-lowering drugs has risen substantially in most countries. This change in attitude has accompanied the appreciation of data from initial observational studies on large cohorts that established the link between elevated serum cholesterol and coronary heart disease and randomized controlled trials of cholesterol lowering that demonstrated improvements in coronary morbidity and mortality seen in patients with or without coronary heart disease. Data are now accumulating on the effects of lowering serum triglyceride levels in improving coronary risk. More studies are still required, but metabolic studies indicate that high serum triglycerides are a marker for the presence of atherogenic small dense low-density lipoproteins. Low concentrations of high-density lipoprotein cholesterol is also a marker for coronary risk, but the case for increasing levels by drugs is unclear. The rationale for the use of lipid-lowering drugs becomes more evident with an understanding of the mechanisms that cause hyperlipidaemia. In addition to serum lipid values, a good clinical history and examination are an essential part of assessing coronary risk. Certain groups, such as women, children, elderly people and patients with genetic hyperlipidaemias or liver or renal disease, need a special approach to therapy. The better tolerability and widespread use of the newer lipid-lowering drugs have raised issues of cost effectiveness. New lipid-lowering drugs are being developed, and there is some evidence that existing lipid-lowering drugs may produce benefit beyond that related to lipid lowering.

Katrina Mackay.et.al

Pancreatic secretion is required for efficient cholesterol absorption by the intestine, but the factors responsible for this effect have not been clearly defined. To identify factors involved and to investigate their role in cholesterol uptake, we studied the effect of Viokase®, a porcine pancreatic extract, on cholesterol uptake into human intestinal Caco-2 cells. Viokase is capable of facilitating cholesterol uptake into these cells such that the level of uptake is 5-fold higher in the presence of solubilized Viokase. This stimulation is time-dependent and is dependent on the presence of bile salt. However, bile salt-stimulated pancreatic cholesterol esterase, which has been proposed to mediate cholesterol uptake, is not fully responsible. The major cholesterol transport activity was purified and identified as pancreatic phospholipase A2. Anti-phospholipase A2 antibodies abolished virtually all of the phospholipase A2 and cholesterol transport activity of solubilized Viokase. We demonstrate that both phospholipase A2 and cholesterol esterase increase cholesterol uptake by hydrolyzing the phosphatidylcholine that is used to prepare the cholesterol-containing micelles. In the absence of cholesterol esterase or phospholipase A2, uptake of cholesterol from micelles containing phosphatidylcholine is not as efficient as uptake from micelles containing phospholipase A2-hydrolytic products. These results indicate that phospholipase A2 may mediate cholesterol absorption by altering the physical-chemical state of cholesterol within the intestine.

The serum cholesterol level is determined mainly by cholesterol synthesis in the liver and clearance of cholesterol-containing lipoproteins and also by the amount of cholesterol absorbed from the intestine. This is demonstrated by the fact that inhibition of cholesterol absorption can decrease serum cholesterol, specifically low density lipoprotein cholesterol (1, 2). The intestinal cholesterol pool has two sources; typically one-third comes from the diet, and the remainder is endogenous cholesterol from bile (3, 4). Cholesterol absorption is not complete and varies widely among individuals; in humans, the percent of cholesterol load absorbed in the intestine has been estimated to vary from 15 to 75% (4), and individuals respond differently to changes in dietary cholesterol (5). This variation suggests that metabolic or genetic factors regulate absorption.

Although cholesterol absorption has been widely studied, the multiple factors involved are not fully understood. However, the absolute requirement for bile is established; bile salts are necessary for solubilization of cholesterol from the oil phase into micelles, from which it is available for absorption (6, 7). Pancreatic secretions also appear to be required. Many studies have shown that giving pancreatic enzymes as a dietary supplement increases fat absorption in patients with pancreatic insufficiency, and one report has specifically demonstrated that enzyme supplementation increases cholesterol absorption in these patients (8). Pancreatectomized dogs and humans have low plasma cholesterol, which can be increased by feeding raw pancreas or pancreatin, a pancreatic extract preparation (9,10).

Of the pancreatic proteins, cholesterol esterase (CEase),1 also known as bile salt-stimulated lipase and carboxyl ester lipase, has received most attention as having a potential role in cholesterol absorption. CEase has a wide substrate specificity, hydrolyzing tri-, di-, and monoglycerides and phospholipids in vitro (11). It also hydrolyzes cholesterol esters, which form a small part of dietary cholesterol and cannot be absorbed without prior hydrolysis to free cholesterol (12). Its role in absorption of free cholesterol has been under debate for many years with conflicting evidence regarding its importance in vivo (13, 14). In vitro, human intestinal Caco-2 cells have been used as a model for cholesterol uptake into the intestinal mucosa. Lopez-Candales et al.(15) reported that CEase stimulated cholesterol uptake from egg phosphatidylcholine (PC) vesicles by Caco-2 cells, whereas Huang and Hui (16) found no stimulation using a similar system. However, the latter study was performed at suboptimal concentrations of bile salt (15). Shamir et al. (17) also found no indication that CEase increased unesterified cholesterol uptake from egg PC or monoolein vesicles. Disruption of the CEase gene in mice confirmed the role of CEase in hydrolysis of cholesterol ester but found no evidence of a role for CEase in the absorption of free cholesterol (18).

The demonstrated importance of pancreatic proteins, combined with increasing data against a role for CEase in unesterified cholesterol uptake, motivated this study to investigate the presence in pancreas of proteins other than CEase which facilitate absorption of free cholesterol. A commercially available porcine pancreatic extract, Viokase®, was used to study cholesterol uptake into Caco-2 cells. Viokase has been used to increase lipid absorption in patients with pancreatic insufficiency (19). We describe the identification of the major cholesterol transport activity in the extract as pancreatic phospholipase A2 and investigate the mechanism by which this enzyme facilitates cholesterol uptake in this model system

John E Heidrich.et.al

Pancreatic cholesterol esterase has three proposed functions in the intestine: 1) to control the bioavailability of cholesterol from dietary cholesterol esters; 2) to contribute to incorporation of cholesterol into mixed micelles; and 3) to aid in transport of free cholesterol to the enterocyte. Inhibitors of cholesterol esterase are anticipated to limit the absorption of dietary cholesterol. The selective and potent cholesterol esterase inhibitor 6-chloro-3-(1-ethyl-2-cyclohexyl)-2-pyrone (figure 1, structure 1) was administered to hamsters fed a high cholesterol diet supplemented with radiolabeled cholesterol ester. Hamsters were gavage fed 3H-labeled cholesteryl oleate along with inhibitor 1, 0-200 micromoles. Twenty-four hours later, hepatic and serum radioactive cholesterol levels were determined. The ED50 of inhibitor 1 for prevention of the uptake of labeled cholesterol derived from hydrolysis of labeled cholesteryl oleate was 100 micromoles. The toxicity of inhibitor 1 was investigated in a 30 day feeding trial. Inhibitor 1, 100 micromoles or 200 micromoles per day, was added to chow supplemented with 1% cholesterol and 0.5% cholic acid. Clinical chemistry urinalysis and tissue histopathology were obtained. No toxicity differences were noted between control and inhibitor supplemented groups.

Inhibitors of cholesterol esterase may be useful therapeutics for limiting cholesterol absorption.

Julian C.-H. Chen.et.

The structure of pancreatic cholesterol esterase, an enzyme that hydrolyzes a wide variety of dietary lipids, mediates the absorption of cholesterol esters, and is dependent on bile salts for optimal activity, is determined to 1.6 Å resolution. A full-length construct, mutated to eliminate two N-linked glycosylation sites (N187Q/N361Q), was expressed in HEK 293 cells. Enzymatic activity assays show that the purified, recombinant, mutant enzyme has activity identical to that of the native, glycosylated enzyme purified from bovine pancreas. The mutant enzyme is monomeric and exhibits improved homogeneity which aided in the growth of well-diffracting crystals. Crystals of the mutant enzyme grew in space group C2, with the following cell dimensions: a ) 100.42 Å, b ) 54.25 Å, c ) 106.34 Å, and! ) 104.12°, with a monomer in the asymmetric unit. The high-resolution crystal structure of bovine pancreatic cholesterol esterase (Rcryst ) 21.1%; Rfree ) 25.0% to 1.6 Å resolution) shows an R-! hydrolase fold with an unusual active site environment around the catalytic triad. The hydrophobic C terminus of the protein is lodged in the active site, diverting the oxyanion hole away from the productive binding site

and the catalytic Ser194. The amphipathic, helical lid found in other triglyceride lipases is truncated in the structure of cholesterol esterase and therefore is not a salient feature of activation of this lipase. These two structural features, along with the bile salt-dependent activity of the enzyme, implicate a new mode

of lipase activation.

Siju et al., (2006)

Isolation of intact high quality RNA suitable for RT-PCR from black pepper is greatly hindered by the presence of polyphenols and polysaccharides. These compounds adversely affect the sensitivity of virus detection by RT-PCR. The present study evaluated the effect of sodium sulphite in enhancing RNA yield and quality in a modified acid guanidium thiocyanate-phenol-chloroform (AGPC) protocol. The results were compared with the standard AGPC method and RNeasy Plant Mini Kit (Qiagen) for detection of Cucumber mosaic virus through RT-PCR. The addition of sodium sulphite in the extraction buffer increased the sensitivity of virus detection. Higher sensitivity of detection (than obtained from the kit) was seen when sodium sulphite was used at 0.5%. Similar levels of sensitivity were also observed for the detection of Cucumber mosaic virus from Piper longum.

Sunila et al., (2003)

Alcoholic extract of the fruits of the plant Piper longum and its component piperine was studied for their immunomodulatory and antitumor activity. Alcoholic extract of the fruits was 100% toxic at a concentration of 500 μg/ml to Dalton's lymphoma ascites (DLA) cells and 250 μg/ml to Ehrlich ascites carcinoma (EAC) cells. Piperine was found to be cytotoxic towards DLA and EAC cells at a concentration of 250 μg/ml. Alcoholic extract and piperine was also found to produce cytotoxicity towards L929 cells in culture at a concentration of 100 and 50 μg/ml, respectively. Administration of alcoholic extract of Piper longum (10 mg/dose/animal) as well as piperine (1.14 mg/dose/animal) could inhibit the solid tumor development in mice induced with DLA cells and increase the life span of mice bearing Ehrlich ascites carcinoma tumor to 37.3 and 58.8%, respectively. Administration of Piper longum extract and piperine increased the total WBC count to 142.8 and 138.9%, respectively, in Balb/c mice. The number of plaque forming cells also enhanced significantly by the administration of the extract (100.3%) and piperine (71.4%) on 5th day after immunization. Bone marrow cellularity and α-esterase positive cells were also increased by the administration of Piper longum extract and piperine

Gauthaman et al., (2001)

Dried pulverized bark of Terminalia arjuna Linn (TA) was administered orally to Wistar albino rats (120-150 g) in two doses [500 and 750 mg/kg in 2% carboxy methyl cellulose (CMC)], 6 days per week for 12 weeks. Thereafter, rats were sacrificed either for determination of baseline changes in cardiac endogenous antioxidant compounds [superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT)] or the hearts were subjected to oxidative stress associated with in vitro ischemic-reperfusion injury (IRI). There was significant increase in the baseline contents of thiobarbituric acid reactive substance (TBARS) (a measure of lipid peroxidation) with both doses of TA. However, only in the 500 mg/kg treated group, this was accompanied by a simultaneous increase in SOD, GSH and CAT levels, but not in the 750 mg/kg treated group, where only CAT was raised. Significant rise in myocardial TBARS and loss of SOD, CAT and GSH (suggestive of increased oxidative stress) occurred in the vehicle-treated hearts subjected to in vitro IRI. Only hearts, harvested from the 500 mg/kg rats treated rats, were significantly protected from oxidative stress, when subjected to in vitro IRI. The results suggest that crude bark of TA augments endogenous antioxidant compounds of rat heart and also prevents oxidative stress associated with IRI of the heart

E.W.C. Chan .et.al.,(2006)

Methanol extracts of fresh tea leaves from a lowland plantation in Malaysia were screened for total phenolic content (TPC) and antioxidant activity (AOA). AOA evaluation included 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging ability, ferric-reducing antioxidant power (FRAP), and ferrous-ion chelating (FIC) ability. Ranking, based on TPC and AOA, was as follows: shoots > young leaves > mature leaves. TPC and AOA of lowland leaves were comparable to those of highland plants. A green tea produced by drying young leaves in a household microwave oven for 4 min showed significantly higher TPC and AOA than did four commercial brands of green and black tea

Raza et al., (2007)

Both the anti- and pro-oxidant effects of tea catechins, have been implicated in the alterations of cellular functions which determine their chemoprotective and therapeutic potentials in toxicity and diseases. Here, we have studied the protective mechanism (s) of three main green tea catechins namely, epicatechin (EC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG) on free radical induced oxidative degradation of membrane lipids and proteins under in vitro conditions using isolated cell free fractions from rat liver. In addition, we have also studied the effects of the tea catechins on 2-deoxyribose degradation in the presence of Fenton and Haber-Weiss oxidants. Glutathione S-transferase and cytochrome P450 2E1 activities and lipid peroxidation were found to be markedly inhibited by tea catechins. These catechins also inhibited the reactive oxygen species formation and oxidative carbonylation of subcellular proteins induced by a physiological oxidant, 4-hydroxynonenal. EGCG and the other catechins showed a time and concentration-dependent effects on the degradation of 2-deoxyribose in the presence of Fenton oxidants. Our results indicate that tea catechins prevent molecular degradation in oxidative stress conditions by directly altering the subcellular ROS production, glutathione metabolism and cytochrome P450 2E1 activity. These results may have implications in determining the chemotherapeutic use of tea catechins in oxidative stress related diseases

Dunja Horžić et al., (2008)

The popularity of tea is increasing on the global aspect because of its role as a significant source of phenolic compounds in human diet. The purpose of this study was to determine and compare the phenolic and methylxanthine composition as well as the antioxidant capacity of white, green, Oolong and black teas, and chamomile and linden infusions depending on the extraction conditions (water temperature and multiple extractions). The content of total phenols and total flavonoids in teas and herbal infusions was determined by using UV/vis spectrophotometric methods, whilst individual polyphenols (phenolic acids and flavan-3-ols) and methylxanthines were identified and quantified by using high performance liquid chromatography coupled with photodiode array detection. In order to determine the antioxidant capacity of teas the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging assays were applied. The highest content of phenolic compounds was determined in green tea, which also demonstrated the highest antioxidant capacity, whilst herbal infusions were characterised with the lowest content of phenolic compounds, as well as the lowest antioxidant capacity. The highest content of caffeine, as the most abundant methylxanthine, was determined in black tea. Extraction at 100 °C is the most effective to extract the highest content of polyphenols and methylxanthines in all studied teas

Nihal Turkmen et al., (2005)

Effect of the use of water and different organic solvents such as acetone, N,N-dimethylformamide (DMF), ethanol or methanol at various concentrations on the total polyphenol content and antioxidant activity was studied for the black tea and mate tea. Polyphenol contents of extracts were determined using ferrous tartrate (method # 1) and Folin-Ciocalteu (method # 2) assays. For black tea, 50% DMF extract showed the highest polyphenol content of 131.9 mg/g and 99.8 mg GAE/g by method # 1 and method # 2, respectively. For mate tea, 50% acetone showed the highest polyphenol content of 132.5 mg/g and 120.4 mg GAE/g by method # 1 and method # 2, respectively. Fifty percent ethanol extract from mate tea and 50% acetone from black tea had the greatest antioxidant activity. The results showed that solvent with different polarity had significant effect on polyphenol content and antioxidant activity. A high correlation between polyphenol content and antioxidant activity of tea extracts was observed.

Ghosh et al., (2004)

Ribonucleases (RNases), which are essential for cleavage of RNA, may be cytotoxic due to undesired cleavage of RNA in the cell. The quest for small molecule inhibitors of members of the ribonuclease superfamily has become indispensable with a growing number exhibiting unusual biological properties. Thus, inhibitors of RNases may serve as potential drug candidates. Green tea catechins (GTC), particularly its major constituent (−)-epigallocatechin-3-gallate (EGCG), have reported potential against cell proliferation and angiogenesis induced by several growth factors including angiogenin, a member of the RNase superfamily. This study reports the inhibition of bovine pancreatic ribonuclease A (RNase A) by EGCG and GTC. This has been checked qualitatively by an agarose gel based assay. Enzyme kinetic studies with cytidine 2′,3′ cyclic monophosphate as the substrate have also been conducted. Results indicate substantial inhibitory activity of a noncompetitive nature with an inhibition constant of 80 μM for EGCG and 100 μM for GTC measured in gallic acid equivalents

Huafu Wang et al., (2000)

The three main categories of tea: green, black and oolong, result from different processing procedures. In recent years tea has attracted more and more attention because of reported health benefits, in particularly as an antioxidant, but also as an anticarcinogenic and antiarteriosclerotic agent. It is generally believed that flavonoids are mainly responsible for these actions. Tea is now consumed throughout the world not just as a popular beverage, but, because its extracts have been prepared in a variety of physical forms, for example, strong infusions, soft extracts and powders, it is now widely available in a range of food, beverage, and toiletry and cosmetic products1

George et al., (2002)

Substrates for synthetic and hydrolytic pancreatic juice cholesterol esterase (sterol ester hydrolase, EC 3.1.1.13), activities were solubuized in micelles of phosphatidylcholine alone or mixed micelles of phosphatidylcholine and a bile acid. The comparative effectiveness of various bile acids in solubilizing the substrates, cholesterol and oleic acid, or cholesterol oleate, was measured turbidimetrically, and the effects of the same bile acids on enzymatic activity were quantitatively determined. In esterification studies, dihydroxy bile acids solubuized substrates as effectively as trihydroxy bile acids. However, only with the latter group, cholic acid and its conjugates, was there significant cholesterol esterification. Comparable results were obtained in hydrolysis studies; essentially no splitting of cholesterol oleate occurred in the absence of trihydroxycholanic acids. Even when cholesterol oleate was effectively solubuized in mixed micelles of glycodeoxycholate and phospholipid, no enzymatic hydrolysis of the substrate occurred until taurocholate was added. Thus, cholic acid and its conjugates appear to be cofactors for pancreatic juice cholesterol esterase.

Data obtained by microtitration of fatty acids and thin-layer silicic acid chromatography of the enzyme digests indicated that the bile acid did not complex with either the fatty acid or cholesterol substrates. The presence of taurocholate effectively prevented tryptic (trypsin, EC 3.4.4.4) and chymotryptic (chymotrypsin, EC 3.4.4.5) inactivation of cholesterol esterase, even though general proteolysis of pancreatic proteins was not effected. In the absence of taurocholate, trypsin addition resulted in complete loss of cholesterol esterase activity within 10 min. It appears, therefore, that the specific requirement of trihydroxy bile acids for cholesterol esterase activity, and the protective effect of taurocholate against proteolytic inactivation of this enzyme, are due to the formation of a specific bile acid-enzyme complex.

Pham et al., (

Green tea extract (GTE) was extracted from raw green tea by using solvent extraction with traditional heating method (SETM) and microwave-assisted extraction (MAE method). Several factors such as solvents (alcohol aquaus), material: solvent ratio (1/5-1/15), pH, extraction temperature, immersion and extraction time of both methods were studied. In same conditions, MAE method gave higher yield in much shorter time than SETM, 82.56% in 360 seconds and 62.14% in 180 minutes, respectively. GTE from MAE method had total polyphenols concentration higher (36%) than that of SETM. Consequently, MAE method was found to be much more effective than SETM in quality of GTE, time and energy consumption.

Turkmen et al., (2007)

Black tea was extracted for 2, 8 and 18 h with absolute acetone, N,N-dimethylformamide (DMF), ethanol and methanol and their 50% aqueous solutions. The extracts were screened for total polyphenol contents, antioxidant and antibacterial activities. The polyphenol content of the extracts was found to be in the range of 0.44-114.01 mg gallic

acid equivalents (GAE)/g dry weight tea, depending on the solvent used and the length of

the extraction process. In general, aqueous acetone or DMF extracts displayed the highest

polyphenol contents and antioxidant activity, while absolute acetone was the least

efficient solvent. Antioxidant activities of tea extracts tested using the reducing power

and 2,2-diphenyl-1-picryhydrazyl (DPPH) radical methods ranged from 0.09 to 1.18 and

from 2.60 to 95.42 %, respectively, depending on the extraction conditions and the

antioxidant activities correlated well with the polyphenol concentrations. Aqueous

solvent black tea extracts also possessed antibacterial activity, depending on the solvent

used and bacterial species tested. Staphylococcus aureus was found to be the most

sensitive to all tea extracts, except for the methanol extract. Tea extracts were not

effective against Y. enterocolitica, L. monocytogenes and E. coli O157:H7.

Gomes et al., (1994)

Investigations were carried out to evaluate the effect of the hot water extract of black tea (Camellia sinensis (L.) O. Kuntze (Theaceae) on streptozotocin (STZ)-induced diabetes in rats. The extract significantly reduced the blood glucose level and was found to possess both preventive and curative effects on experimentally produced diabetes in rats. The study reveals that, like green tea, black tea also possesses antidiabetic activity

Jyotirmoy Ghosh.et.al., (2009)

Acetaminophen (APAP) causes acute and chronic renal failure. The mechanisms leading to hepatic injury have been extensively studied, but the molecular mechanisms regarding APAP-induced nephro-toxicity are poorly defined. In earlier studies, we have demonstrated that arjunolic acid (AA) possesses protective roles against chemically induced organ pathophysiology. The purpose of the present study was to explore whether AA plays any protective role against APAP induced acute renal toxicity; and if so, what pathways it utilizes for the mechanism of its protective action. Exposure of rats with a nephro-toxic dose of APAP altered a number of biomarkers (like blood urea nitrogen and serum creatinine levels, etc.) related to renal oxidative stress, decreased antioxidant activity, elevated renal tumor necrosis factor-α and nitric oxide levels. AA treatment both pre- and post to APAP exposure protected the alteration of these biomarkers, compensated deficits in the antioxidant defense mechanisms, and suppressed lipid peroxidation in renal tissue. Investigating the inherent molecular signaling of this pathophysiology and its protection, we found that the mitochondrial pathway was not activated during APAP-induced cell death as no dissipation of mitochondrial membrane potential or release of cytochrome C was detected in the respective experiments. Our experimental evidence suggests that APAP-induced nephro-toxicity is a caspase-dependent process that involves activation of caspase-9 and caspase-3 in the absence of cytosolic cytochrome C release. These results provide evidence that inhibition of NO overproduction and maintenance of intracellular antioxidant status may play a pivotal role in the protective effects of AA against APAP-induced renal damage. AA represents a potential therapeutic option to protect renal tissue from the detrimental effects of acute acetaminophen overdose.

Rethinam.et.al.,(2006)

Present study was to evaluate the effect of methanolic extract of Terminalia arjuna (TA) on diclofenac sodium induced gastric ulcer in experimental rats.

Animals were induced for gastric ulcer with diclofenac sodium (DIC) (80 mg/kg bodyweight in water, orally) and treated orally with TA in various doses ranging from 100 mg/kg bodyweight to 500 mg/kg bodyweight. The effective dose was 400 mg/kg bodyweight, since this dose elicited a maximum reduction in lesion index. The gastroprotective effect of TA was assessed from volume of gastric juice, pH, free and total acidity, pepsin concentration, acid output in gastric juice, the levels of non-protein sulfhydryls (NP-SH), lipid peroxide (LPO), reduced glutathione (GSH), and activities of enzymic antioxidants-super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and myeloperoxidase (MPO) in gastric mucosa. The levels of DNA, protein bound carbohydrate complexes-hexose, hexoseamine, sialic acid, fucose in gastric mucosa and gastric juice and the levels of RNA in gastric mucosa were assessed. The stomach tissues were used for adherent mucus content and also for the histological examination.

Results

A significant reduction in lesion index was observed in ulcer induced animals treated with TA (DIC + TA) compared to ulcerated rats (DIC). A significant increase was observed in pH, NP-SH, GSH, enzymic antioxidants, protein bound carbohydrate complexes, adherent mucus content, nucleic acids with a significant decrease in volume of gastric juice, free and total acidity, pepsin concentration, acid output, LPO levels and MPO activities in DIC + TA rats compared to DIC rats. Histological studies confirmed the gastroprotective activity of TA.

Conclusion

From the data presented in this study it could be concluded that T. arjuna acts as an gastroprotective agent probably due to its free radical scavenging activity and cytoprotective nature

Hiroshi Kuriharan et al., (2006)

A naturally decaffeinated tea, Camellia sinensis var. ptilophylla (cocoa tea), has long been popular in southern China as a healthy beverage. Our experiments indicate that a single oral administration of 500 mg/kg of cocoa tea extract suppresses increases in plasma triacylgycerol (TG) levels when fed with 5 mL/kg of olive or lard oil in mice and that the inhibition rates are 22.9% and 31.5%, respectively, compared with controls. Under the same condition, cocoa tea extract did not affect the level of plasma free fatty acid. Likewise, the extract reduced the lymphatic absorption of lipids at 250 and 500 mg/kg. Also, cocoa tea extract and polyphenols isolated from cocoa tea inhibit pancreatic lipase. These findings suggest that cocoa tea has hypolipemic activity, which may be due to the suppression of digestive lipase activity by the polyphenols contained within the tea.

Chan et al., (1999)

These studies were designed to test the hypolipidemic activity of green tea epicatechins (GTE) isolated from jasmine green tea. In Experiment 1, three groups of hamsters were given a semisynthetic diet containing 200 g lard/kg and 1 g cholesterol/kg for 4 wk. The control group received distilled water, and the other two groups received either 15 g/L green tea water extract (GTWE) or 5.0 g/L GTE solution. Both the GTWE and GTE groups had lower concentrations of serum total cholesterol (TC) and triacylglycerols (TG) than the controls (P < 0.05). In Experiment 2, four groups of hamsters received tap water as the drinking fluid, but they were given the same high fat and cholesterol diet supplemented with 0 (control), 1.1, 3.4 or 5.7 g GTE/kg diet. The hypolipidemic effect of jasmine GTE was dose dependent. In Experiment 3, the time-course of changes in serum TC and TG was monitored in hamsters given the high fat diet supplemented with 5.7 g GTE/kg in comparison with that of controls. The hypolipidemic effects of dietary GTE were evident after feeding for 2 wk. Dietary supplementation of GTE did not affect liver fatty acid synthase. However, GTE-supplemented hamsters had higher fecal excretions of total fatty acids, neutral sterols and acidic sterols compared with the control group. In Experiment 4, hamsters were fed nonpurified diet; the control group drank distilled water, and the GTE group drank distilled water containing 5.0 g GTE/L. No differences in activities of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and intestinal acyl CoA:cholesterol acyltransferase were observed. This study suggests that the hypolipidemic activity of GTE is not due to inhibition of synthesis of cholesterol or fatty acid but is most likely mediated by its influence on absorption of dietary fat and cholesterol

Santosh et al.,(1992)

Recently, we and others showed that the components of green tea may be useful cancer chemopreventive agents. It has been suggested that (-)-epigallocatechin-3-gallate (EGCG), the major constituent in green tea, may possess antitumor-promoting and/or anticarcinogenic effects in rodent tumor bioassay systems. During the chemical analysis of various green tea products, we found a traditionally preserved preparation of green tea used by tribes in the Himalayan region of Sikkim, India that was rich in EGCG. EGCG was isolated from this tea product, and its inhibitory effects were evaluated against the binding of topically applied 3H-labeled polycyclic aromatic hydrocarbons (PAHs) to epidermal DNA and 12-O-tetra-decanoylphorbol-13-acetate (TPA) caused induction of epidermal ornithine decarboxylase (ODC) activity in Sencar mice, the short-term markers of tumor initiation and tumor promotion, respectively. Preapplication of EGCG resulted in significant inhibition (p < 0.05) in the binding of [3H] PAH to epidermal DNA. Similarly, the topical application of EGCG resulted in significant inhibition (p < 0.005) in TPA-caused induction of epidermal ODC activity. In further studies, we assessed the anti-skin tumor-initiating effect of EGCG in Sencar mice in an initiation-promotion protocol. The application of EGCG before challenge with 7,12-dimethylbenz[a]anthracene as tumor initiator resulted in significant reduction both in percentage of mice with tumors and number of tumors per mouse compared with a non-EGCG-pretreated group of animals. The results of the present study suggest that the green tea preparation from Sikkim may be a good source for the isolation of EGCG and that this compound may have significant potential as a cancer chemopreventive agent.

David Y. Hui et al.,(2005)

Many enzymes and transport proteins participate in cholesterol absorption. This review summarizes recent results on several proteins that are important for each step of the cholesterol absorption pathway, including the important roles of: (i) pancreatic triglyceride lipase (PTL), carboxyl ester lipase (CEL), and ileal bile acid transporter in determining the rate of cholesterol absorption; (ii) ATP binding cassette (ABC) transporters and the Niemann-Pick C-1 like-1 (NPC1L1) protein as intestinal membrane gatekeepers for cholesterol efflux and influx; and (iii) intracellular membrane vesicles and transport proteins in lipid trafficking through intracellular compartments prior to lipoprotein assembly and secretion to plasma circulation.

Zesheng Zhang et al., (2001)

The present study was to investigate the mechanisms by which hawthorn fruit lowers serum cholesterol in hamsters. The control group was fed a semisynthetic diet containing 0.1% cholesterol while the tested group was maintained on the same diet but supplemented with 0.5% hawthorn fruit aqueous ethanolic extract for 4 weeks. Serum total cholesterol (TC) and triacylglycerols (TG) were decreased by 10 and 13%, respectively, in hawthorn fruit group as compared with the control (P<0.05). Supplementation of hawthorn fruit aqueous ethanolic extract led to greater excretion of both neutral and acidic sterols. Further enzymatic assays suggest the mechanisms by which hawthorn fruit decreases serum cholesterol involve a greater excretion of bile acids mediated by up-regulation of hepatic cholesterol 7α-hydroxylase (CH) activity, and an inhibition of cholesterol absorption mediated by down-regulation of intestinal acyl CoA:cholesterol acyltransferase (ACAT) activity.

G.F. Ngando Ebongue et al., (2006)

The mesocarp of mature oil palm fruit undergoes intensive triglycerides hydrolysis upon abscission and bruising. This generates such a high amount of free fatty acids that the oil might become unfit for human consumption without appropriate refining. The lipase (EC 3.1.1.3) involved in the breakdown of the oil is not stable after homogenization of the tissue in aqueous buffers. In this study, we have devised a solvent-based procedure that allowed us to obtain fractions with stable lipase activity. Using these fractions, we have determined the optimal conditions for assaying mesocarp lipase activity. The activity was highest at a temperature of 35 °C and a pH of 9. The lipase was found to be strictly calcium dependent. The specific activity of the lipase measured in optimal conditions was found to be 33 μmol fatty acids released min-1 mg-1 protein using olive oil as substrate. The mesocarp contains about 190 U of lipase g-1 fresh weight. This activity was found to be inhibited by the lipase inhibitor tetrahydrolipstatin (THL), suggesting that the lipase is a serine hydrolase.

V. Chithra1 and S. Leelamma et al ., (2004)  

The effect of the administration of coriander seeds (Coriandrum sativum) on the metabolism of lipids was studied in rats fed a high fat diet with added cholesterol. The spice had a significant hypolipidemic action. The levels of total cholesterol and triglycerides decreased significantly in the tissues of the animals of the experimental group which received coriander seeds. Significant increases in -hydroxy, -methyl glutaryl CoA reductase and plasma lecithin cholesterol acyl transferase activity were noted in the experimental group. The level of LDL + VLDL cholesterol decreased while that of HDL cholesterol increased in the experimental group compared to the control group. The increased activity of plasma LCAT, enhanced hepatic bile acid synthesis and the increased degradation of cholesterol to fecal bile acids and neutral sterols appeared to account for its hypocholesterolemic effect.

Coriander - Spices - -hydroxy - -methyl glutaryl CoA reductase - Plasma lecithin cholesterol acyl transferase - Cholesterol - Triglycerides - Hepatic and Fecal bile acids

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