Evidence Possible Mechanisms Effects Polyphenols On Plasma Lipoproteins Biology Essay

Polyphenols are produced by workss to function a battalion of functions including growing, reproduction, pigmentation and protection from pathogens. To day of the month, over 8000 different polyphenolic constructions have been elucidated ( Bravo, 1998 ) . It is found that they all portion a common chemical construction and differ merely in their extra linkages with other compounds, including sugars, aminoalkanes, organic acids and lipoids. As they are omnipresent in the works land, these compounds are common components of the human diet ( particularly in fruits, veggies, java, tea, vino, cocoa and soy ) . Surveies indicate that polyphenols may be of great importance in disease intervention and bar, chiefly due to their antioxidant belongingss.

Ingested polyphenols may be either absorbed in the little bowel or colon, and/or excreted in the fecal matters or piss. In the little bowel polyphenols can come in the mucous membrane straight while in the colon they foremost need to be digested into smaller constructions ( Bravo, 1998 ) . Once absorbed, polyphenols and their metabolites are transported to the liver where farther digestion may take topographic point. Finally polyphenols or their metabolites may be transported to the tissues where they exert their effects or else be Figure 1.Chemical constructions of polyphenols ( Manach, Scalbert, Morand, Remesy, & A ; Jimez, 2004 )

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excreted by being shuttled to the kidneys or incorporated into gall.

The good effects of polyphenols were ab initio recognized from in vitro surveies ( which showed their antioxidant belongingss ) and epidemiological surveies ( notably surveies sing the Mediterranean diet and the Gallic paradox ) which indicated that the ingestion of polyphenol-rich nutrients correlated with a low incidence of cardiovascular disease. Clinical tests, carnal experiments and mechanistic surveies followed ; the consequences from these are conflicting. In this essay the grounds ( concentrating on human surveies ) and possible mechanisms for the effects of polyphenols from five different foods/beverages ( vino, tea, olive oil, java, and cocoa ) on plasma lipoproteins will be reviewed in relation to cardiovascular wellness.

Polyphenols and LDL oxidization

As one can see from table 1, one of the most of import results found in most surveies look intoing the effects of devouring polyphenol-rich foods/beverages on plasma lipoproteins is a decrease in LDL oxidizability. It is believed that LDL oxidization plays a major function in early atherogenesis and in fact oxidized LDL has been detected in atherosclerotic lesions ( Aviram, Maor, Keidar, & A ; et Al, 1995 ) . LDL oxidization occurs within the arterial wall, where cells such as smooth musculuss cells and macrophages can oxidise LDL. Furthermore the interaction of LDL with macrophages under conditions of oxidative emphasis activates enzymes ( cellular oxygenases ) which in bend produce reactive oxygen/nitrogen species which are besides capable of oxidising LDL ( Aviram, Rosenfeld, Etzioni, & A ; Levy, 1996 ) . Conversely, human serum paraoxonase protects LDL from oxidization. As polyphenols have been shown to be capable of protecting LDL from oxidization, they may hold a really of import preventative function in cardiovascular diseases.

The protection against LDL oxidization is believed to be due to the addition in plasma phenoplasts following polyphenol-rich nutrient ingestion ; these can adhere to LDL and protect it from oxidization. Their ability to move as antioxidants in this scenario is related to their chemical constructions every bit good to their localizaiton in the LDL atom. Several mechanisms may account for this suppression of LDL oxidization: scavenging free groups, chelating metal ions, sparing of other antioxidants and increasing/preserving paraoxonase activity ( Cordova, Jackson, Berke-Schlessel, & A ; Sumpio, 2005 ) . Polyphenols may scavange free groups by moving as cut downing agents, as H atom donating molecules and as vest O quenchers. Polyphenols contain both lipotropic and hydrophilic medieties and therefore are able to move against free groups generated both in aqueous and lipid environments. In this regard, different polyphenols have different divider coefficients ( aqueous/lipophylic compartments ) in plasma and within the LDL atom and therefore different polyphenols are expected to hold different antioxidant capablenesss. A survey done with glabadrin ( hydrophobic ) and catechin ( less lipophylic ) found that after incubation of LDL with the two, merely glabadrin was found to adhere to LDL in important sums ( Belinky, Aviram, Fuhram, & A ; et Al, 1998 ) .

The antioxidant consequence of polyphenols might besides be through the chelation of passage metal ions, therefore cut downing the ability of the metal to bring forth free groups ( Nardini, D’Aquino, Tamassi, & A ; et Al, 1995 ) . Another mechanism is by saving vitamin E and carotenoids in the LDL atom, therefore heightening the antioxidant consequence. In vitro surveies have demonstrated that incorporation of glabridin into LDL reduced the ingestion of I?-carotene and lycopene by 41 % and 50 % severally ( Belinky, Aviram, Fuhram, & A ; et Al, 1998 ) .

Polyphenols might besides suppress LDL oxidization by protecting or promoting serum paraoxonase activity by diminishing the content of lipid peroxides, which can oxidize and therefore inactivate paraoxonase ( Fuhrman & A ; Aviram, 2001 ) . By protecting the degrees of serum paraoxonase, the hydrolysis of arterial cells and LDL associated lipid peroxides is promoted. Polyphenol-induced fading of LDL oxidization could besides ensue from suppression of cellular oxygenases ( such as NADPH oxidase ) thereby cut downing macrophage oxidative emphasis. This has been confirmed in vitro by incubating macrophages with glabridin, catechin and quercetin ; all three lead to a decrease in the ability of the cell to oxidise LDL ( Aviram & A ; Fuhrman, LDL oxidization by arterial wall macrophages depends on the antioxidative position in the lipoprotein and in the cells: function of prooxidants vs. antioxidants. , 1998 )

One must maintain in head that in nutrients, polyphenols exist in combination and therefore they may move additively or synergistically, via several mechanisms to protect against LDL oxidization.

Red Wine

The Gallic typically consume a diet which is high in concentrated fats, yet they have a low mortality rate from ischaemic bosom disease ( Renaud & A ; de Lorgeril, 1992 ) . This observation is frequently referred to as ‘the French paradox ‘ and is attributed to their high ingestion of ruddy vino. Though moderate [ write sum and ref ] ingestion of intoxicant in general has been found to assist forestall arterial sclerosis [ ref ] ruddy vino exerts a stronger consequence than other alcoholic drinks [ ref [ ] .

Several constituents of ruddy vino exert beneficiary effects on the cardiovascular system and the ground why ruddy vino produces more marked effects compared to other alcoholic drinks is believed to be it s polyphenolic content. The polyphenols in ruddy vino are largely derived from grape teguments and seeds and include flavanols ( quercitin and myricetin ) , flavanols ( catechin and epicatechin ) , anthocyannins, stilbenes ( resveratrol ) , hydroxynnamates and the hydroxybenzoates ( Cordova, Jackson, Berke-Schlessel, & A ; Sumpio, 2005 ) . Red vinos by and large contain between 1000 and 4000 milligram phenolics/L ( Burns, Gardner, O’Neil, & A ; et Al, 2000 ) .

It is believed that phenolic compounds in vino act as antioxidants protecting the organic structure from harm caused by free groups ( Kanner, Frankel, Granit, German, & A ; Kinsella, 1994 ) . In vitro surveies have besides demonstrated that these compounds my prevent oxidative alterations of LDL ( Frankel, Waterhouse, & A ; Teissedre, 1995 ) On the other manus human intercession surveies have yielded conflicting consequences, as can be seen in table 1. ( Nigdikar, Williams, Griffin, & A ; Howard, 1998 ) look into all found that ruddy vino ingestion for two hebdomads led to a decrease in LDL oxidization ( addition in lag clip ) while the white vino and vodka groups displayed no alteration. Entire cholesterin, HDL, LDL and TAG degrees were unaffected. Since it has been widely demonstrated that intoxicant ingestion increases HDL cholesterin ( Hartung, Foreyt, & A ; Reers, 1990 ) the writers of this survey speculate that the deficiency of consequence on this parametric quantity was due to the continuance of the survey ( 2 hebdomads ) being two short.

( Avellone, et al. , 2006 ) recorded an addition in HDL degrees following 4 hebdomads of vino ingestion, together with an addition in apoA1 and decreases in LDL/HDL ratio ; TAG, entire cholesterin and LDL degrees were unaffected. This was a cross-over survey and the altered parametric quantities returned to baseline values after 4 hebdomads of surcease of wine consumption.

( Cordain, et al. , 200 ) studied the possible positive effects of wine ingestion in reasonably corpulent ( BMI ) adult females with impaired insulin sensitiveness, nevertheless no effects on plasma lipoids were observed. This survey nevertheless did non mensurate LDL oxidizability. The writers speculate that the deficiency of alterations in plasma lipid parametric quantities, particularly HDL degrees, might be due to the extra organic structure fat contradicting the good effects of intoxicant ingestion, as tends to go on for insulin sensitiveness. This observation was corroborated by another survey of over 600 adult females, where it was noted that intoxicant ingestion was correlated with an addition in HDL cholesterin in healthy weight adult females but non in corpulent adult females ( Fricker, Fumeron, Chabchoub, & A ; et Al, 1990 )

( Cartron & A ; et Al, 2003 ) demonstrated that ruddy wine lead to an addition in plasma antioxidant capacity ( pAOC ) after three to four hours following a individual consumption of ruddy vino ; nevertheless it was found that after 3 hebdomads of day-to-day vino ingestion this value really decreased. The writers nevertheless commented that this evident lessening might be due to the topic ‘s high baseline values.

apoA1 values increased which supports other surveies describing that HDL degrees are increased following ruddy wine ingestion ( Avellone, et al. , 2006 ) . This addition was non observed in topics given white vino or bubbly, therefore bespeaking that polyphenols in ruddy vino have a cardinal function in this consequence. Since old surveies have found that moderate intoxicants intake in general has the ability to promote apoA1 degrees ( Rimm, Williams, Fosher, Criqui, & A ; Stampfer, 1999 ) so this survey might propose that intoxicant and ruddy vino polyphenols may move synergistically to increase apoA1plasma degrees.

After three hebdomads of ruddy vino ingestion, TAG concentration was found to be decreased, nevertheless LDL degrees were unchanged. Unlike what has been reported by ( Nigdikar, Williams, Griffin, & A ; Howard, 1998 ) , this survey found no alteration in LDL oxidizability. There was besides no noticeable alteration in LDL vitamin E and ubiquinol whose degrees normally reflect extent of oxidization ( due to their oxidation-reduction belongingss ) . This survey therefore concludes that the good effects of ruddy vino with respects to CVD hazard are due to the effects on lipid and lipoprotein invariables and non by an antioxidant action.

Tea

Tea contains a figure of different bioactive chemicals ; nevertheless it peculiarly rich in polyphenols particularly catechins and their derived functions. Fresh bluish green foliages are rich in epicatechin ( EC ) , epigallocatechin ( EGC ) , epicatechin gallate ( ECG ) and epigallocathechin gallate ( EGCG ) . Tea leaves besides contain plyphenol oxidase enzymes is separate beds of the foliages and when the foliages are broken during industrial tea production, the cathechins come in contact with this enzymnes are are later oxidised, organizing the flavanols theaflavins and thearubingins. Due to the different procedures involved in the production of green tea and black tea, the former has a high concentration of catechins and a low concentration of theaflavins and theaarubingins while the latter is hapless in catechins but rich in theaflavins and thearubingins.

It has been demonstrated that catechins are absorbed intestinally ( Okushio, Matxumuto, Kohri, Suzuki, Nanjo, & A ; Hara, 1996 ) and that in worlds, plasma degrees peak two to four hours after consumption ( Yang, Chem, Lee, Balentine, Kuo, & A ; Schantz, 1998 ) . Tea polyphenols have been demonstrated to be powerful antioxidants in in vitro surveies, and they may accomplish this via five different mechanisms ( Higdon & A ; Frei, 2003 ) . The first mechanism might be through free extremist scavenging, particularly sing the fact that EGCG and EGC have lower decrease potencies than vitamin E, therefore bespeaking that they might be superior negatron givers than vitamin E ( Jovanavic, Steenken, & A ; Simic, 1996 ) . In vitro surveies have demonstrated that green tea and black tea polyphenols are able to expeditiously scavenge the azotic oxide extremist, with green tea being five times more powerful than black tea ( Paquay, Haenen, Stender, Wiseman, Tijburg, & A ; Bast, 2000 ) . The antioxidant activity of catechins is believed to be due to 1 ) an ortho-dihydroxyl group in the B ring, which aids negatron delocalization and stabilizes the extremist signifier ( Rice-Evans, Miller, & A ; Paganga, 1996 ) ; 2 ) they are by and large H2O soluble, nevertheless they are still able to efficaciously suppress lipid peroxidation in liposomes and LDL ( in in vitro surveies ) ( Kondo, Kurihara, & A ; Fukuhara, 2001 ) .

Tea polyphenols are able to chelate metal ions, and this may an of import mechanism which explains their antioxidant consequence since this implies that they are able to suppress transition metal-catalyzed free extremist formation ( Rice-Evans & A ; Miller, Antioxidant belongingss of phenolic compounds. , 1997 )

Another possible path which has been demonstrated in vitro is through suppression of written text factor activation ( Nuclear Factor-kB and Activator Protein-1 ) ; the former induces the written text of inflammatory cistrons ( Pan, Lin-Shiau, Ho, Lin, & A ; Lin, 2000 ) while the latter ‘s activity has been implicated in tumour publicity ( Chung, Huang, Meng, Dong, & A ; Yang, 1999 ) .

Tea polyphenols are besides believed to be able to suppress certain enzymes whose activity tends to increase oxidative emphasis. The three chief enzyme of involvement are inducible azotic oxide synthase ( iNOS ) ; lipoxygenases and Coxs ; and xanthine oxidase [ x1 ] . iNOS generates big sums of azotic oxide which can respond with O in vivo to organize harmful azotic oxide-derived oxidizers. Lipoxygenases and Coxs may cooxidize other molecules, ensuing in increased oxidative emphasis in some tissues. Xanthine oxidase catalyzes the oxidization of hypoxanthine and xantine to uric acid, bring forthing reactive O species as by merchandises.

Finally, in vitro surveies have demonstrated that tea polyphenols may bring on stage II enzymes and antioxidant enzymes ( Higdon & A ; Frei, 2003 ) . Phase II enzymes by and large have a detoxifying action while antioxidant enzymes such as catalase and superoxide dismutase carry out antioxidant functions in the organic structure.

Human surveies sing the consequence of tea ingestion on lipoproteins are scarce. ( Ishikawa & A ; et Al, 1997 ) describe a decrease in LDL oxidizability, which might be explained by the mechanisms explained above. The survey found no alteration in HDL, TAG and entire cholesterin degrees. Similarly ( Gomikawa & A ; Ishikawa, 2000 ) found that ingestion of green tea lead to a decrease in LDL oxidizability together with a lessening in LDL degrees while HDL degrees were unchanged. On the other manus ( van het Hof, de Boer, Wiseman, Lien, Weststrate, & A ; Tijburg, 1997 ) reported no alteration in LDL oxidizability or in LDL, HDL or TAG degrees.

Olive oil

Olive oil contains a assortment of bioactive molecules, the chief good 1s believed to be oleic acid, phenoplasts and squalene ( Owen, et al. , 2000 ) . These have all been found to posses antioxidant belongingss and the high degrees of monounsaturated fatty acids found in olive oil have a cardiovascular benefit in their ain right.

The entire phenolic content of olive has been measured to be in the scope of 196-500 mg/kg, with excess virgin oil holding higher phenoplast content than refined virgin oil ( Owen, et al. , 2000 ) . Major phenols in olive oil are hyroxytyrosol, tyrosol, oleuropein and ligstroside ( Owen, et al. , 2000 ) . Hydroxytyrosol and oleuropein have been demonstrated to posses free extremist scavenging belongingss and the ability to suppress LDL oxidization in vitro ( Owen, et al. , 2000 ) . Apart from their direct antioxidant activity, olive oil polyphenols have been shown to suppress xanthine oxidase activity while seed oils had small consequence ( Owen, et al. , 2000 )

It is believed that the decrease in LDL oxidizability brought approximately by olive oil phenoplasts is due to the binding of the polyphenols to the LDL atom and their subsequent antioxidant action. In fact it has been found that polyphenols edge to LDL addition in dose dependent mode with the sum of polyphenols in the olive oil consumed ( Fuller & A ; Jialal, 1994 ) . Specifically it has been found that in worlds, hyroxytyrosol and its metabolites are capable of adhering to human LDL after olive oil ingestion ( De la Torre, Jauregui, Castellote, Lamuela-Raventos, Covas, & A ; Casalas, 2006 ) .

Human intercession surveies entering the positive effects of olive oil ingestion on cardiovascular hazard and lipoprotein parametric quantities are many ( Covas, 2007 ) . In order for this consequence to be ascribed to the polyphenol fraction, so one must look at surveies comparing olive oils with similar MUFA degrees but different polyphenols degrees. ( De la Torre R. , 2004 ) conducted a controlled, dual blind, cross-over, randomised clinical trail utilizing three similar olive oils with increasing phenolic concentration. It was found that when devouring olive oil without polyphenols, there was no alteration in LDL oxidizability ; when devouring olive oil with 68mg/Kg polyphenols at that place was a decrease in LDL oxidizability ; and when devouring an olive oil with 150mg/Kg polyphenols, the decrease in LDL oxidizability was even higher. Furthermore merely when devouring the olive oil incorporating the highest sums of polyphenols was an addition in HDL degrees recorded.

Coffee

While there are over a thousand different compounds in java, the three chief ingredients responsible for physiological effects are caffeine, the diterpene alcohols kahweol and cafestol and the polyphenols. The chief polyphenol in java is chlorogenic acid, an ester of caffeic acid and quinic acid, and is an in vitro antioxidant ( Natella, Nardini, Belelli, & A ; Scaccini, 2007 ) . It is estimated that a 180mL cup of brewed java contains 396mg of polyphenols while instant java around 316mg ( Bonita, Mandarano, Shuta, & A ; Vinson, 2007 ) . In vitro surveies indicate that java polyphenols can adhere to LDL and therefore protect them from oxidization ( Bonita, Mandarano, Shuta, & A ; Vinson, 2007 ) nevertheless human intercession surveies are controversial.

( Yukawa, et al. , 2004 ) reported that after 1 hebdomad of java ingestion, LDL oxidizability was reduced, together with a decrease in entire and LDL cholesterin. Similarly ( Natella, Nardini, Belelli, & A ; Scaccini, 2007 ) demonstrated a decrease in LDL oxidizability after imbibing a individual cup of 200mL of filtered java.

It seems that different types of javas might hold really different impacts on cardiovascular wellness. In fact while the surveies mentioned above study a positive impact after the ingestion of filtered java, a meta-analysis of randomized controlled clinical tests analyzing the effects of java ingestion on serum cholesterin concluded that “ ingestion of unfiltered, but non filtered, java additions serum degrees of entire and LDL cholesterin ” ( Ha, He, Appel, Whelton, Suh, & A ; Klag, 2001 ) .

Cocoa and Chocolate

Cocoa is one of the richest flavinoid-conaining nutrients available ; in fact over 10 per centum of chocolate pulverization by weight is flavinoids ( Keen, 2001 ) . The flavinoids nowadays in cocoa/chocolate are chiefly catechin and epicatechin ( in a ratio of about 6:1 ) which are besides present in ruddy vino and green tea. Surveies in worlds have shown that the concentration of these flavinoids in the plasma extremums after about one hr following consumption and returns to baseline after about six hours ( Keen, 2001 ) . The observations from in vitro surveies that cocoa/chocolate polypohenols act as antioxidants ( Keen, 2001 ) have besides been replicated in vivo: both ( Mathur, Devaraj, Grundy, & A ; Jialal, 2002 ) and ( Osakabe, 2001 ) found that cocoa/chocolate ingestion resulted in decreased LDL oxidizability. As for other polyphenols, it is believed that this consequence is chiefly brought approximately by 1 ) the direct antioxidant consequence of the polyphenols and 2 ) the saving consequence on other antioxidants such as vitamin E and C. Other mechanisms described antecedently might besides be in consequence.

Decision

Assorted epidemiological surveies have demonstrated an opposite association between the ingestion of polyphenol-rich nutrients and the hazard of cardiovascular diseases. With respects to plasma lipoproteins, the mechanism by which these compounds are thought to cut down the hazard for cardiovascular disease is chiefly by their ability to move as antioxidant, cut downing the susceptibleness of LDL to oxidization, which is a causative procedure in coronary artery disease. Polyphenols might besides cut down entire and LDL cholesterin and increase HDL in some instances. In vitro surveies have confirmed that these compounds are powerful antioxidants and may so hold the ability to cut down the susceptibleness of LDL to oxidization. However, bioavailability surveies have shown that ingested polyphenols are quickly and extensively metabolized by the organic structure, and this brings to oppugn the utility of in vitro informations.

Human intercession surveies concentrating on the effects of polyphenols on lipoproteins have characteristically yielded conflicting consequences. Assorted factors might explicate this. First, bioavailability differs greatly among polyphenols and the same polyphenols are known to hold different bioavailability harmonizing to the signifiers in which they are present in the nutrient ( Manach, Mazur, & A ; Scalbert, 2005 ) . Furthermore high inter-individual variableness in the efficaciousness of enteric soaking up and metamorphosis has been recorded ( Meyer & A ; et Al, 2004 ) . Most polyphenols have been shown to be quickly eliminated one time absorbed and therefore whether the polyphenol-rich food/beverage is consumed as portion of a repast or in fasting conditions may hold a pronounced effect on whether or non their effects are observed. Besides, non all surveies measure the concentration of the polyphenols in the food/beverage administered, and therefore it is hard to compare surveies. It is known that for a given nutrient point, the sums and nature of polyphenols present may change significantly harmonizing to seasonal fluctuation, clime, ripeness, and nutrient processing and readying.

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