Hydroxycinnamic acids do not prevent aortic atherosclerosis in hypercholesterolemic golden Syrian hamsters
Introduction
Phenolic substances are present in large quantities in plant foods. They are important components in the human diet, as their daily intake can reach up to 800 mg depending on the consumption of specific food and beverages such as red wine for exemple (Beecher, 1999). Besides vitamines C, E, A and carotenoids, polyphenols may account for at least part of the health benefits associated with the consumption of fresh fruits, vegetables, tea and red wine (Duthie et al., 2000). A major class of phenolic non flavonoid compounds such as hydroxycinnamic acids is present in human diet in representative amounts Dao and Friedman, 1992, Onyeneho and Hettiarachchy, 1992; they are encountered in wine, coffee, tea leaves, whole grains and in many vegetables and fruits in which they contribute to color and sensory properties such as biterness and astrigency (Macheix et al., 1990). Caffeic acid and sinapic acid are among the major hydroxycinnamic acids present in wine; sinapic acid, which is a potent antioxidant (Andreasen et al., 2001) is present in significant quantities in red wine (up to 2.10−3 g/L) (Cabanis et al., 1998); caffeic acid has also been identified as one of the active antioxidant (Abu-Amsha et al., 1996) of red wine (up to 26.10−3 g/L) (Cabanis et al., 1998); apples were known to contain up to 510 mg/kg chlorogenic acid (Macheix and Fleuriet, 1998). The potential health benefits of the hydroxycinnamic acids and derivatives have mostly been related to their effective antioxidant capacity. These compounds are of growing interest since they are potent antioxidants and inhibit low-density lipoprotein (LDL) oxydation in vitro Frankel et al., 1993, Nardini et al., 1995, Meyer et al., 1998a, Meyer et al., 1998b, properties which are associated to their ability to scavenge free radicals and chelate metals and which are a known feature of the atherosclerotic plaque where oxidised LDL contribute to the development of fatty lesions (Steinberg et al., 1989). The ability of hydroxycinnamic acids to inhibit oxidation of human LDL decrease in the following order: caffeic acid > sinapic acid > ferulic acid > p-coumaric acid Steinberg et al., 1989, Meyer et al., 1998a, Meyer et al., 1998b, Natella et al., 1999. An increased consumption of phenolics has been correlated with a reduced risk of cardiovascular diseases and certain types of cancers Bravo, 1998, Duthie and Crozier, 2000. Hence it is expected that diseases caused by cholesterol oxidation may be prevented by them Frankel et al., 1993, Laranjinha et al., 1992, Laranjinha et al., 1994, Maxwell et al., 1994, Frankel et al., 1995 and particularly atherosclerosis (Steinberg et al., 1989). It has also been shown that wine phenolic compounds such as resveratrol Belguendouz et al., 1998, Frémont et al., 1999, quercetin Meyer et al., 1998a, Meyer et al., 1998b, Yamamoto et al., 1999, catechins and caffeic acid Meyer et al., 1998a, Meyer et al., 1998b exerted considerable antioxidant potency toward LDL oxidation in vitro. Elsewhere, results from studies of red wine phenolics in humans have also been inconsistent Nigdikar et al., 1998, Abu-Amsha Caccetta et al., 2000; moreover, Revell et al. (2002) reported that resveratrol, catechin, epicatechin and quercetin protect LDL oxidation in vitro but not ex vivo. Such studies reflected in part the use of ex vivo methodologies to assess in vivo effects of phenolics ingestion on LDL oxidation and therefore atherosclerosis. Lipid peroxidation is indeed an initial step in the atherosclerosis pathology and evidence is increasing that oxidative modification of LDL is involved (Steinberg et al., 1989). The early lesions of atherosclerosis consist of subendothelial accumulations of cholesterol-engorged macrophages, called foam cells (Steinberg et al., 1989); accumulation of oxidatively modified LDL in the artery intima contributes significantly to monocyte recruitement and foam cell formation, which form fatty streaks Aqel et al., 1985, Rosenfeld et al., 1987 and which are also present in atherosclerotic plaques Gown et al., 1986, Jonasson et al., 1986, Masuda and Ross, 1990. In humans, such fatty streak lesions can usually be found in the aorta, coronary and cerebral arteries (Lusis, 2000). It has been shown that Golden Syrian hamsters fed a fat-rich diet develop dyslipidemia and atherosclerotic plaques, similar in many respects to human atheroma Filip et al., 1987, Nistor et al., 1987. This model was chosen (i) to overcome such controversy, (ii) because both vitamin E and catechin were reported to inhibit development of aortic lesions in Golden Syrian hamsters (Xu et al., 1998) and (iii) because of its responsiveness to plasma cholesterol lowering and anti-atherogenic interventions Spady and Dietschy, 1985, Spady et al., 1986, Kowala et al., 1991. Moreover hamster has similar plasma lipoprotein distribution to humans and LDL as major plasma cholesterol carrier. Apart from ethanol, the phenolic compounds are involved in the cardioprotective capacity of red wine Das et al., 1999, Agewall et al., 2000 and one possible explanation is that they slow the progression of atherosclerosis by acting as antioxidant toward LDL Frankel et al., 1993, Kinsella et al., 1993, Vinson et al., 2001. This study represents a part of an investigation aiming at determining what class(es) of phenolic compounds is (are) efficient in the prevention of early atherosclerosis. Since, at present, there is no direct evidence that hydroxycinnamic acids exert a beneficial cardioprotective effect in vivo, we have studied their effects and that of a de-alcoholized red wine phenolic extract (RWPE) on this model. For a comparative purpose, chlorogenic acid, the parent compound of caffeic acid, was also tested. In order to induce a peroxidative stress, the high cholesterol and high fat diet was rendered deficient in vitamin C and E and in selenium.
The aim of the present study was to trigger off the arterial wall response to such a stress (fatty streak formation and aortic atherosclerosis emergence) and then to look at the modulation of this effect by RWPE, caffeic acid, sinapic acid and chlorogenic acid.
Section snippets
Preparation of red wine phenolic extract (RWPE)
The RWPE dry powder from red French wine (Corbières A.O.C.) was prepared according to the following procedure: briefly, phenolic compounds were adsorbed on a preparative column (20% Polyclar AT , 10% silica G gel, 70% silica 60 gel; this adsorbant mix was treated by HCl 12N during 30 minutes and rinsed by twice distilled water until neutrality) then the wine was added to the column and an elution with twice distilled water was realized to flush out sugars, acids and minerals. In a second time
General
There were some differences in the final body weight among the five groups (Table 2). The group receiving sinapic acid (SA) was slightly heavier although all the groups did not differ in the food consumption.
Plasma lipids and apolipoproteins
Plasma TC was lower in hamsters that received RWPE than in controls and in those that received hydroxycinnamic acids (Table 3). Whatever the experimental group, treatment was without effect on plasma HDL-C and Apo-A1 (Table 3); RWPE affected Apo-B concentration, whereas CA, SA and CHA did
Discussion
Epidemiological studies have shown that the reduced mortality rate from cardiovascular disease (CVD) in southern France is approximately half the rate in other European countries in spite of a high consumption of saturated fats Klatsky et al., 1974, Tunstall-Pedoe et al., 1999. In such a case, cardioprotection has been demonstrated to be correlated with an increased intake of red wine Rimm et al., 1996, Renaud and de Lorgeril, 1992 rather than white wine and other liquor such as beer and
References (66)
- et al.
Ingestion of red wine significantly increases plasma phenolic acid concentrations but does not acutely affect ex vivo lipoprotein oxidizability
American Journal of Clinical Nutrition
(2000) - et al.
Phenolic contents of various beverages determines the extent of inhibition of human serum and low density lipoprotein oxidation in vitro: identification and mechanism of action of some cinnamic acid derivatives from red wine
Clinical Science
(1996) Catalase
Methods in Enzymology
(1984)- et al.
Does a glass of red wine improve endothelial function?
European Heart Journal
(2000) - et al.
Antioxidant effects of phenolic rye (Secale cereale L.) extracts, monomeric hydroxycinnamates, and ferulic acid dehydrodimers on human low-density lipoproteins
Journal of Agricultural and Food Chemistry
(2001) - et al.
Identification of macrophages and smooth muscle cells in human atherosclerosis using monoclonal antibodies
Journal of Pathology
(1985) Flavonoids in foods
- et al.
Interaction of transresveratrol with plasma lipoproteins
Biochemical Pharmacology
(1998) Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance
Nutrion Reviews
(1998)- et al.
Human Apo A-I and rat transferrin are the principal plasma proteins that bind wine catechins
Journal of Agricultural and Food Chemistry
(2002)
Protection against free radical injury by selenoenzymes
Pharmacological Therapeutics
Tables de composition
Levels of flavan-3-ols in french wines
Journal of Agricultural and Food Chemistry
Chlorogenic acid content of fresh and processed potatoes determined by ultraviolet spectrophotometry
Journal of Agricultural and Food Chemistry
Cardioprotection of red wine: role of phenolic antioxidants
Drugs Experimental and Clinical Research
Plant-derived phenolic antioxidants
Current Opinion in Lipidology
Plant polyphenols in cancer and heart disease: implications as nutritional antioxydants
Nutrition Research Reviews
Cellular events in the development of vascular atherosclerotic lesions induced by experimental hypercholesterolemia
Atherosclerosis
Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine
Lancet
Principal phenolic phytochemicals in selected California wines and their antioxidant activity in inhibiting oxidation of human low-density-lipoproteins
Journal of Agricultural and Food Chemistry
Antioxidant activity of resveratrol and alcohol-free wine polyphenols related to LDL oxidation and polyunsaturated fatty acids
Life Sciences
Human atherosclerosis: II. Immunocytochemical analysis of the cellular composition of human atherosclerotic lesions
American Journal of Pathology
Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque
Arteriosclerosis
Comparison of red wine extract and polyphenol constituents on endothelin-I synthesis by cultured endothelial cells
Clinical Science
Possible mechanisms for the protective role of antioxidants in wine and plant foods
Food Technology
Alcohol consumption before myocardial infarction
Annals of Internal Medicine
Doxazosin and cholestyramine similarly decrease fatty streak formation in the aortic arch of hyperlipidemic hamsters
Atherosclerosis
A direct hplc separation of wine phenolics
American Journal of Enology and Viticulture
Lipid peroxidation and its inhibition in low density lipoproteins: quenching of cis-parinaric acid fluorescence
Archives of Biochemistry and Biophysics
Reactivity of dietary phenolic acids with peroxyl radicals: antioxidant activity upon low density lipoprotein peroxidation
Biochemical Pharmacology
Atherosclerosis
Nature
Phenolic acids in fruits
Cited by (26)
Regression of atherosclerosis with apple procyanidins by activating the ATP-binding cassette subfamily A member 1 in a rabbit model
2017, AtherosclerosisCitation Excerpt :The second purpose of this study was to evaluate whether the anti-atherosclerotic effect is obtained not only by a cholesterol-lowering effect, but also through other mechanisms. Mechanisms for the anti-atherosclerotic capacity of procyanidins have been explained by in vitro and in vivo studies as the inhibition of several substances or reactions [9,11–18,21], in addition to their cholesterol-lowering effect. However, it remains unclear whether the efficacy regarding atherosclerosis is mainly attributable to mechanisms other than a cholesterol-lowering effect, since an obvious reduction in the serum LDL-C level is usually obtained by procyanidins administration [22].
Effect of supplementation of purple pigment from anthocyanin-rich corn (Zea mays L.) on blood antioxidant activity and oxidation resistance in sheep
2012, Livestock ScienceCitation Excerpt :Consistent with the present results, no significant change in the plasma TAC was observed in lactating cows fed anthocyanin-rich corn (Hosoda et al., in press). However, it has been reported that the consumption of anthocyanin leads to increases in blood TAC in monogastric animals (Auger et al., 2004; Mazza et al., 2002), a finding that disagrees with our present result. The conflict between the present result and the results of previous studies with monogastric animals might be explained by the poor absorption of anthocyanin by sheep due to their different digestion system (Dijkstra et al., 2005).
Effects of Hydroxytyrosol on Atherosclerotic Lesions in apoE-Deficient Mice
2010, Olives and Olive Oil in Health and Disease PreventionPlum juice, but not dried plum powder, is effective in mitigating cognitive deficits in aged rats
2009, NutritionCitation Excerpt :The absence of flavonoids in the dried plum powder may have also contributed to the lack of effect in dried plum powder-fed rats in the MWM, because flavonoids typically possess greater bioactivity than hydroxycinnamates. Compared with hydroxycinnamates, flavonoids are more potent antioxidants [32] and are also more protective in models of vascular oxidative stress, inflammation [33], and atherosclerosis [34]. Furthermore, another investigation using a similar dried plum powder found that the concentration of neochlorogenic acid and chlorogenic acid in the dried plum powder was considerably less than that reported for dried plums [35].
Coffee and cardiovascular disease: In vitro, cellular, animal, and human studies
2007, Pharmacological ResearchCitation Excerpt :In confirmation of our study a French group did not find that CGA or caffeic acid had any effect on lipids or atherosclerosis in this same hamster model. These phenolic acids did increase plasma antioxidant capacity and thus had an in vivo antioxidant effect [52]. Hypertension is a major risk factor for CHD, stroke and congestive heart failure [57,58].
Effects of anthocyanin-rich purple potato flakes on antioxidant status in F344 rats fed a cholesterol-rich diet
2007, British Journal of Nutrition