Sunday, 24 November 2013

Phytochemicals and Coronary heart disease

Cardiovascular Disease
Cardiovascular disease is defined as medical conditions affecting the cardiovascular system, including heart, blood vessels(arteries and veins).
I. Coronary heart disease
Coronary heart disease is defined as a condition of narrowing coronary arteries that lead to blockage of the blood flow in the arteries as a result of hardening arterial wall, cholesterol building up in the arteries, chemicals, such as cadmium clog up arteries, etc. affecting the small blood vessels that supply blood and oxygen to the heart. Coronary heart disease (CHD) is the leading cause of death in the United States.
Phytochemicals to prevent Coronary heart disease
1. Omega-3, 6,9 fatty acids are phytochemincals in the class of Lipids, found abundantly in dark-green leafy vegetables, grains, legumes, nuts, etc.
a. Vascular smooth muscle tone
In the investigation of the comparative effects of omega-3, omega-6 and omega-9 fatty acids on vascular smooth muscle tone, showed that Docosahexaenoic acid (1-255 microM) and eicosapentaenoic acid (31-255 microM) inhibited phenylephrine-induced contractions, (8-63%) and (20-65%), respectively, which were not altered by indomethacin, NDGA, or by removal of the endothelium. Linoleic acid (18:2n6) and arachidonic acid (20:4n6) also induced significant relaxation. Therefore, fatty acid-induced relaxation of the rat aorta is specific to polyunsaturated fatty acids, 20:5n3, 22:6n3, 18:2n6 and 20:4n6, according to “Effects of omega-3, omega-6 and omega-9 fatty acids on vascular smooth muscle tone” by Engler MB.(69)
b. Systolic blood pressure, triglycerides and LDL cholesterol
In the ccomparison of the cardiovascular risk-reduction potential of three major polyunsaturated fatty acids in a double-blind study. showed that for the diet supplemented with EPA plus DHA compared with the linoleic acid diet systolic blood pressure fell 5.1 mm Hg (p = 0.01); plasma triglyceride and VLDL cholesterol fell by 39% (p = 0.001) and 49% (p = 0.01), respectively; and LDL cholesterol rose by 9% (p = 0.01). There were no significant changes with the diet supplemented with alpha-linolenic acid. The net effect on cardiovascular risk therefore is complex and the systolic blood pressure reduction was substantial, according to “n-3 fatty acids of marine origin lower systolic blood pressure and triglycerides but raise LDL cholesterol compared with n-3 and n-6 fatty acids from plants” by Kestin M, Clifton P, Belling GB, Nestel PJ.(70)
c. Cardiovascular effects
In the comparison of the effects of alpha-linolenic acid (ALA, C18:3n-3) to those of eicosapentaenoic acid (EPA, C20:5n-3) plus docosahexaenoic acid (DHA, C22:6n-3) on cardiovascular risk markers in healthy elderly subjects, found that Both n-3 fatty acid diets did not change concentrations of total-cholesterol, LDL-cholesterol, HDL-cholesterol, triacylglycerol and apoA-1 when compared with the oleic acid-rich diet. However, after the EPA/DHA-rich diet, LDL-cholesterol increased by 0.39 mmol/l (P = 0.0323, 95% CI (0.030, 0.780 mmol/l)) when compared with the ALA-rich diet. Intake of EPA/DHA also increased apoB concentrations by 14 mg/dl (P = 0.0031, 95% CI (4, 23 mg/dl)) and 12 mg/dl (P = 0.005, 95% CI (3, 21 mg/dl)) versus the oleic acid and ALA-rich diet, respectively. Except for an EPA/DHA-induced increase in tissue factor pathway inhibitor (TFPI) of 14.6% (P = 0.0184 versus ALA diet, 95% CI (1.5, 18.3%)), changes in markers of hemostasis and endothelial integrity did not reach statistical significance following consumption of the two n-3 fatty acid diets, according to “Effects of alpha-linolenic acid versus those of EPA/DHA on cardiovascular risk markers in healthy elderly subjects” by Goyens PL, Mensink RP.(71)
d. Antioxidant, antimicrobial activities
In the investigation of the hexane extract from different parts in several Hypericum species, found that The antioxidant activity of all hexane extracts was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method. The results indicate that hexane extracts from different parts of H. scabrum possess considerable antioxidant activity. The highest radical scavenging activity was detected in seed, which had an IC50 = 165 microg/mL. The antimicrobial activity of the extracts of those samples were determined against seven Gram-positive and Gram-negative bacteria (Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, S. epidermidis, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae), as well as three fungi (Candida albicans, Saccharomyces cerevisiae, and Aspergillus niger), according to “Antioxidant, antimicrobial activities and fatty acid components of flower, leaf, stem and seed of Hypericum scabrum” by Shafaghat A.(72)
e. Obesity
in the determination of whether obesity modifies the association between plasma phospholipid polyunsaturated fatty acids (PUFAs) and markers of inflammation and endothelial activation in Multi-Ethnic Study of Atherosclerosis (MESA) participants, found that the modifying effect of obesity on the association of plasma PUFAs with IL-6 and sICAM-1 suggests differences in fatty acid metabolism and may also have implications in dietary fatty acid intake for obese individuals, particularly for linoleic and EPAs. Further study is warranted to confirm and explain the strong associations of dihomo-γ-linolenic acid (DGLA) with inflammatory and endothelial activation markers, according to “Obesity modifies the association between plasma phospholipid polyunsaturated fatty acids and markers of inflammation: the Multi-Ethnic Study of Atherosclerosis” by Steffen BT, Steffen LM, Tracy R, Siscovick D, Hanson NQ, Nettleton J, Tsai MY.(73)
2. α-Carotene is a phytochemincal in the class of Carotenes, belonging to the group of Carotenoids (tetraterpenoids), found abundantly in carrots, pumpkins, maize, tangerine, orange, etc.
 a. Metabolic syndrome
In the examination of the association between serum antioxidant status and MetS. NHANES 2001-2006 cross-sectional data among adults aged 20-85 y were analyzed (n = 3008-9099). MetS was defined with the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and also by elevated homeostatic model assessment insulin resistance (HOMA-IR), C-reactive protein (CRP) and hyperuricemia, found that Serum antioxidants included retinol, retinyl esters, carotenoids [α-carotene, β-carotene (cis+trans), β-cryptoxanthin, lutein+zeaxanthin, total lycopene], vitamin E, and vitamin C. MetS (NCEP ATP III) prevalence in U.S. adults was 32.0% among men and 29.5% among women. Adults with MetS had consistently lower serum carotenoid concentrations compared with those without MetS, even after controlling for total cholesterol and TG among other potential confounders, according to “Serum antioxidant status is associated with metabolic syndrome among U.S. adults in recent national surveys” by Beydoun MA, Shroff MR, Chen X, Beydoun HA, Wang Y, Zonderman AB.(74)
b. Cardiovascular disease
In the investigation of to whether serum carotenoid concentrations predict mortality among US adults. The study consisted of adults aged ≥20 years enrolled in the Third National Health and Nutrition Examination Survey, 1988 to 1994, with measured serum carotenoids and mortality follow-up through 2006 (N = 13,293), indicated that in a random survival forest analysis, very low lycopene was the carotenoid most strongly predictive of all-cause mortality, followed by very low total carotenoids. α-Carotene/β-cryptoxanthin, α-carotene/lutein+zeaxanthin and lycopene/lutein+zeaxanthin interactions were significantly related to all-cause mortality (P < .05). Low α-carotene was the only carotenoid associated with cardiovascular disease mortality (P = .002). No carotenoids were significantly associated with cancer mortality, according to “Low-serum carotenoid concentrations and carotenoid interactions predict mortality in US adults: the Third National Health and Nutrition Examination Survey” by Shardell MD, Alley DE, Hicks GE, El-Kamary SS, Miller RR, Semba RD, Ferrucci L.(75)
3. Resveratrol is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape wine, nuts, peanuts, etc.
a. Cardiovascular diseases
In the revie of reviews some of the key studies, and the known mechanisms for these beneficial effects. Evidence from different experimental studies, including from the authors’ laboratories, and the beneficial effects of polyphenols found in red wine, especially resveratrol in grape skins.
found that Resveratrol benefits include a reduction in cardiovascular morbidity and mortality, lung cancer and prostate cancer by approximately 30% to 50%, 57% and 50%, respectively. Polyphenols possess antioxidant, superoxide-scavenging, ischemic-preconditioning and angiogenic properties. Some of these properties of polyphenols may explain their protective effects on the cardiovascular system, as well as other body organs, according to “Significance of wine and resveratrol in cardiovascular disease: French paradox revisited” by Vidavalur R, Otani H, Singal PK, Maulik N.(76)
b. Cardiovascular health
In the review of Resveratrol (3,4′,5-trihydroxystilbene), a member of natural, plant-derived chemicals known as polyphenols and is attracting increased attention due to its diverse health benefits especially in case of cardiovascular disease, cancer, diabetes and neurological problems, indicated that Recently, resveratrol was found to induce autophagy and regenerate myocardial ischemic tissue treated with stem cells. Overall observation indicates that resveratrol has a high therapeutic potentials for the treatment of cardiovascular diseases, according to “Resveratrol and cardiovascular health” by Das M, Das DK.(77)
c. Oxidative stress and endothelial dysfunction
In the investiagtion of the role of S6K1 in aging-associated endothelial dysfunction and effects of the polyphenol resveratrol on S6K1 in aging endothelial cells, wrote that our data demonstrate a causal role of the hyperactive S6K1 in eNOS uncoupling leading to endothelial dysfunction and vascular aging. Resveratrol improves endothelial function in aging, at least in part, through inhibition of S6K1. Targeting S6K1 may thus represent a novel therapeutic approach for aging-associated vascular disease, according to “Hyperactive S6K1 mediates oxidative stress and endothelial dysfunction in aging: inhibition by resveratrol” by Rajapakse AG, Yepuri G, Carvas JM, Stein S, Matter CM, Scerri I, Ruffieux J, Montani JP, Ming XF, Yang Z.(78) d. Insulin resistance
In the evaluation of the effects of Res on insulin sensitivity and the underlying mechanism, insulin-resistant KKA(y) mice were treated with 2 and 4 g/kg diets of Res for 12 weeks, found that Res intervention reduces blood glucose and serum insulin levels, improves insulin and glucose tolerance, increases serum adiponectin and adiponectin mRNA levels in epididymal adipose tissues, and more importantly, elevates Sirt1, p-AMPK, p-IRS1, and p-AKT levels in liver and soleus muscles, according to “Effects of resveratrol on the amelioration of insulin resistance in KKA(y) mice” by Chen S, Li J, Zhang Z, Li W, Sun Y, Zhang Q, Feng X, Zhu W.(79)
e. Healthy heart and longevity
In the review focuses on the anti-aging aspects of resveratrol, the possible mechanisms of action,
found that resveratrol can induce the expression of several longevity genes including Sirt1, Sirt3, Sirt4, FoxO1, Foxo3a and PBEF and prevent aging-related decline in cardiovascular function including cholesterol level and inflammatory response, but it is unable to affect actual survival or life span of mice, according to “Resveratrol and red wine, healthy heart and longevity” by Das DK, Mukherjee S, Ray D.(80)
f. Anti diabetes
In the evaluation of resveratrol, a polyphenolic SIRT1 activator and its SIRT1 activation in an in vitro fluorescent based assay (EC(50) : 7 μM) and the efficacy of resveratrol was also evaluated in ob/ob mice for its antidiabetic and associated metabolic effects, found that a significant improvement observed in the glucose excursion in the oral glucose tolerance test performed for 120 min; although an insignificant improvement in the triglycerides, total cholesterol, adiponectin and free fatty acid levels was observed at different doses of resveratrol tested. The present findings suggest that resveratrol is an antihyperglycemic agent and drugs similar to resveratrol can be considered as an effective therapeutic adjuvant for the current treatment of diabetes mellitus, according to “Antidiabetic activity of resveratrol, a known SIRT1 activator in a genetic model for type-2 diabetes” by Sharma S, Misra CS, Arumugam S, Roy S, Shah V, Davis JA, Shirumalla RK, Ray A.(81)
4. Oleuropein is a phytochemical in the Tyrosol esters, belonging to The class of Phenolic compounds, found a abundantly in olive oil.
a. Antioxidant activity
In the evaluation of the effect of the isolation of seventeen compounds (1-17) of antioxidant activity of a 70% EtOH extract from the bark of Syringareticulata, found that among the isolated compounds, jaspolyoside (2), oleuropein (4) and 2-(3,4-dihydroxy)-phenylethyl-β-d-glucopyranoside (17), showed the most potent superoxide anion scavenging activity with the EC(50) values of 4.97, 2.57 and 4.97μM, respectively. The structure-activity relationship indicated that the presence of 2-(3,4-dihydroxyphenyl)-ethoxy group is important for exhibiting the activity, according to “Secoiridoid glucosides and related compounds from Syringa reticulata and their antioxidant activities” by Bi X, Li W, Sasaki T, Li Q, Mitsuhata N, Asada Y, Zhang Q, Koike K.(82)
b. Cardiovascular health
In the determination of the effect of oleuropein, one of the polyphenols in olive oil, on vascular smooth muscle cell (SMC) proliferation in vitro, found that Oleuropein inhibited SMC proliferation through a cell cycle block between the G1 and the S phases, which may be regulated by ERK1/2. These results suggest a mechanism by which olive oil consumption may have beneficial effects on cardiovascular mortality by inhibiting SMC proliferation. according to ” Olive oil polyphenol oleuropein inhibits smooth muscle cell proliferation” by Abe R, Beckett J, Abe R, Nixon A, Rochier A, Yamashita N, Sumpio B.(83) c. LDL oxidation resistance
In the comparison of the antioxidative activity of diverse phenolic compounds presented in virgin olive oil on these lipoproteins, found that both virgin olive oil extract enriched in phenolic compounds and phenolic compounds present in olive oil (caffeic acid and oleuropein) are potent antioxidants at very low concentrations. Thus, the beneficial effects of a Mediterranean diet may be partly due to the protective action of these compounds, according to “[Effect of phenolic compounds of virgin olive oil on LDL oxidation resistance].[Article in Spanish]” by Moreno JA, López-Miranda J, Gómez P, Benkhalti F, El Boustani ES, Pérez-Jiménez F.(84)
5. Phytosterols are a subgroup of lipids, the steroid compounds similar to cholesterol in plant, Researchers have found more than 200 of them.
a. Cholesterol
Phytosterols are best best known to have a property in lowering the blood cholesterol, according to the study of ” Scientific Opinion on the substantiation of health claims related to plant sterols and plant stanols and maintenance of normal blood cholesterol concentrations (ID 549, 550, 567, 713, 1234, 1235, 1466, 1634, 1984, 2909, 3140), and maintenance of normal prostate size and normal urination (ID 714, 1467, 1635) pursuant to Article 13(1) of Regulation (EC) No 1924/2006″, posted in EFSA Journak, researchers filed in summary that a cause and effect relationship has been established between the consumption of plant sterols and plant stanols and the reduction of blood cholesterol concentrations.
b. Coronary heart disease
In most case, if a substance have a good effect in lowering blood cholesterol concentration, it may also promote heart health. In a study of ” Plant Sterols and Blood Cholesterol Scientific substantiation of a health claim related to plant sterols and lower/reduced blood cholesterol and reduced risk of (coronary) heart disease pursuant to Article 14 of Regulation (EC) No 1924/20061″ from Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies, Adopted on 11 July 2008, researchers indicated that Elevated low-density lipoprotein (LDL) blood cholesterol is one recognised risk factor for coronary heart disease (CHD). CHD is an important cause of mortality and morbidity. Lowering LDL-cholesterol by dietary intervention has been shown to reduce the risk of coronary heart disease. The Panel considers that the claimed effect of lowering LDL cholesterol is beneficial to human health.
c. Cytotoxic and Antioxidant effects
Phytoecdysteroids are phytochemicals including triterpene saponins, phytosterols, and phytoecdysteroid. In a study of “Phytoecdysteroids of Silene guntensis and their in vitro cytotoxic and antioxidant activity” by Mamadalieva NZ, El-Readi MZ, Janibekov AA, Tahrani A, Wink M. (Source from Institute of the Chemistry of Plant Substances AS RUz, Tashkent, Uzbekistan), posted in PubMed, researchers filed in abstract that
c.1. Cytotoxic effects
The chloroform extract showed potent cytotoxic effects [IC50 values (26.58 +/- 1.88) microg/mL, (20.99 +/- 1.64) microg/mL, and (18.89 +/- 2.36) microg/mL, respectively].
c.2. Antioxidant effect
The new compound 1 was mildly cytotoxic compared to extracts [(127.97 +/- 11.34), (106.76 +/- 7.81), and (203.10 +/- 19.56) microg/mL, respectively]. Water and n-butanol extracts exhibited good antioxidant activities [IC50 values of (68.90 +/- 6.45) microg/mL and (69.12 +/- 5.85) microg/mL, respectively].
6. Matairesinol is a phytochemical in the class of Lignans (phytoestrogens), found abundantly in flax seed, sesame seed, rye bran, strawberries, blackcurrants, broccoli, etc.
a. Cardiovascular healthIn the assessment of the association of phytoestrogens and risk markers of cardiovascular diseases in postmenopausal women, found that the intake of matairesinol and secoisolaiciresinol (SILR) (mean±SD, mg/day) were 0.022±0.006 and 7.30±3.28 respectively. The total phytoestrogens (r=-0.19, p=0.03) and SILR, one specific type of lignans (r=-0.19, p=0.04) consumption in this study were inversely significantly associated with serum glucose level. The dietary formononetin, one specific type of isoflavones was negatively significantly associated with LDL-cholesterol (r=-0.18, p=0.04). There was no significant relationship found between phytoestrogen intake and serum homocysteine level (r=-0.11, p=0.23). Phytoestrogens containing food intake should be encouraged for reducing risk markers of cardiovascular disease in postmenopausal women, according to “Phytoestrogen intake and cardiovascular risk markers in Bangladeshi postmenopausal women” by Saleh F, Afnan F, Ara F, Yasmin S, Nahar K, Khatun F, Ali L.(85)
b. Free radical scavengers
In the examination of the radical and superoxide scavenging activities of oxidized matairesinols,
indicated that the superoxide scavenging activity of the oxidized matairesinols was also demonstrated for the first time. It is assumed that the pKa value of phenol in the oxidized matairesinols affected this activity, according to “Radical and superoxide scavenging activities of matairesinol and oxidized matairesinol” by Yamauchi S, Sugahara T, Nakashima Y, Okada A, Akiyama K, Kishida T, Maruyama M, Masuda T.(86) c. Coronary heart disease (CHD), cardiovascular diseases (CVD), cancer, and all-cause mortality
In the assessment of whether the intakes of 4 plant lignans (lariciresinol, pinoresinol, secoisolariciresinol, and matairesinol) were inversely associated with coronary heart disease (CHD), cardiovascular diseases (CVD), cancer, and all-cause mortality, found that total lignan intake was not associated with mortality. The intake of matairesinol was inversely associated with mortality due to CHD, CVD, cancer, and all causes. We cannot exclude the possibility that the inverse association between matairesinol intake and mortality is due to an associated factor, such as wine consumption, according to “Intakes of 4 dietary lignans and cause-specific and all-cause mortality in the Zutphen Elderly Study” by Milder IE, Feskens EJ, Arts IC, Bueno-de-Mesquita HB, Hollman PC, Kromhout D.(87)
7. Etc. 

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