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Red Grape Seed Extract Improves Lipid Profiles and Decreases Oxidized Low-Density Lipoprotein in Patients with Mild Hyperlipidemia

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Seyed-Mostafa Razavi at University of South Dakota
Seyed-Mostafa Razavi
Sharareh Gholamin at California Institute of Technology
Sharareh Gholamin
Ali Eskandari at Isfahan University of Technology
Ali Eskandari
Nakta Mohsenian
Nakta Mohsenian
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Abstract Hyperlipidemia can lead to atherosclerosis by lipoprotein deposition inside the vessel wall and oxidative stress induction that leads to the formation of atherosclerotic plaque. Oxidized low-density lipoprotein particles (Ox-LDL) have a key role in the pathogenesis of atherosclerosis. The lipid-lowering properties and antioxidants of the grape seed can be beneficial in atherosclerosis prevention. We conducted a randomized double-blind placebo-controlled crossover clinical trial. Fifty-two mildly hyperlipidemic individuals were divided into two groups that received either 200 mg/day of the red grape seed extract (RGSE) or placebo for 8 weeks. After an 8-week washout period, the groups were crossed over for another 8 weeks. Lipid profiles and Ox-LDL were measured at the beginning and the end of each phase. RGSE consumption reduced total cholesterol (-10.68±26.76 mg/dL, P=.015), LDL cholesterol (-9.66±23.92 mg/dL, P=.014), and Ox-LDL (-5.47±12.12 mg/dL, P=.008). While triglyceride and very low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased by RGSE, the changes were not statistically significant. RGSE consumption decreases Ox-LDL and has beneficial effects on lipid profile-consequently decreasing the risk of atherosclerosis and cardiovascular disorders-in mild hyperlipidemic individuals.
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SHORT COMMUNICATIONS
Red Grape Seed Extract Improves Lipid Profiles
and Decreases Oxidized Low-Density Lipoprotein
in Patients with Mild Hyperlipidemia
Seyed-Mostafa Razavi,
1
Sharareh Gholamin,
1,2
Ali Eskandari,
1
Nakta Mohsenian,
1
Amir Ghorbanihaghjo,
3
Abbas Delazar,
4
Nadereh Rashtchizadeh,
3
Maryam Keshtkar-Jahromi,
1,5
and Hassan Argani
4,6
1
Clinical Research and Development Center, Shahid Modarres Hospital;
6
Urology and Nephrology
Research Center; Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2
Department of Neurosurgery, Institute of Stem Cell Biology and Regenerative Medicine,
Stanford University, Stanford, California, USA.
3
Biothechnology Research Center and
4
Drug Applied Research Center, Tabriz University
of Medical Sciences, Tehran, Iran.
5
Department of Internal Medicine, Union Memorial Hospital, University of Maryland,
Baltimore, Maryland, USA.
ABSTRACT Hyperlipidemia can lead to atherosclerosis by lipoprotein deposition inside the vessel wall and oxidative stress
induction that leads to the formation of atherosclerotic plaque. Oxidized low-density lipoprotein particles (Ox-LDL) have a
key role in the pathogenesis of atherosclerosis. The lipid-lowering properties and antioxidants of the grape seed can be
beneficial in atherosclerosis prevention. We conducted a randomized double-blind placebo-controlled crossover clinical trial.
Fifty-two mildly hyperlipidemic individuals were divided into two groups that received either 200 mg/day of the red grape
seed extract (RGSE) or placebo for 8 weeks. After an 8-week washout period, the groups were crossed over for another 8
weeks. Lipid profiles and Ox-LDL were measured at the beginning and the end of each phase. RGSE consumption reduced
total cholesterol (-10.68 –26.76 mg/dL, P=.015), LDL cholesterol (-9.66 –23.92 mg/dL, P=.014), and Ox-LDL (-5.47 –
12.12 mg/dL, P=.008). While triglyceride and very low–density lipoprotein cholesterol were decreased and high-density
lipoprotein cholesterol was increased by RGSE, the changes were not statistically significant. RGSE consumption decreases
Ox-LDL and has beneficial effects on lipid profile—consequently decreasing the risk of atherosclerosis and cardiovascular
disorders—in mild hyperlipidemic individuals.
KEY WORDS: atherosclerosis grape seed extract lipid profile oxidative stress
Cardiovascular disorders are the leading cause of
mortality worldwide. Plasma lipoprotein disorders and
dyslipidemia are long-known risk factors for progression of
atherosclerosis and cardiovascular disease. Lipoprotein de-
position in the intimal layer of arteries causes the formation
of atherosclerotic plaque.
1,2
Additionally, plasma lipid pro-
file changes induce formation of hydroxyperoxide and lysis
of phospholipids, oxysterol, and other lipids.
2
Oxidized low-
density lipoprotein particles (Ox-LDL) have a key role in the
atherosclerosis pathogenesis. The exposure to Ox-LDL
causes endothelial cells to express adhesion molecules that
facilitate monocytes migration to subendothelial layers,
which transform into macrophages and release growth
factors. Exposure to Ox-LDL also triggers smooth muscle cell
and fibroblast proliferation, platelet aggregation, and angio-
tensin II-like effects.
3
Free radical oxygen scavengers play a
role in the coronary artery disease pathophysiology.
1,2,4
Lipid-lowering properties of grape products have been
investigated in many animal and some human studies, some
with promising results, and some investigators have debated
their effect on lipid profiles.
5–9
Antioxidants contained in the
red grape seed extract (RGSE) are able to inactivate su-
peroxide anions and prevent lipid peroxidation.
10
RGSE has
cardioprotective effects against reperfusion-induced injury
by free radicals after ischemia.
2,11
In this study, we evalu-
ated the lipid-lowering properties of RGSE and its effect on
Ox-LDL in mild hyperlipidemic individuals.
A randomized double-blind placebo-controlled clinical
trial was carried out at Shahid Modarres Hospital (Tehran,
Iran). The target population were adults aged 21–64 years,
with triglyceride (TG) >150 mg/dL and total cholesterol
>200 mg/dL. Individuals with severe hyperlipidemia (TG
Manuscript received 12 June 2012. Revision accepted 17 December 2012.
Address correspondence to: Sharareh Gholamin, MD, Department of Neurosurgery,
Institute of Stem Cell Biology and Regenerative Medicine, Stanford University, Lorry
Lokey Research Building (SIM-1), 265 Campus Drive, Cheshier Lab Room #G1115,
Stanford, CA 94305,USA, E-mail: sharar@stanford.edu
JOURNAL OF MEDICINAL FOOD
J Med Food 16 (3) 2013, 255–258
#Mary Ann Liebert, Inc., and Korean Society of Food Science and Nutrition
DOI: 10.1089/jmf.2012.2408
255
>300 mg/dL, total cholesterol >250 mg/dL), body mass
index (BMI) >30 kg/m
2
, heart failure, chronic renal failure,
chronic hepatic disease, malignancy, any lipid-lowering
drug usage, vegetarian diet, alcohol, and cigarette use were
excluded from the study. During a nonrandom sequential
sampling of subjects participating in the screening program
for cardiovascular disease at the hospital’s clinics, 52 sub-
jects were randomly assigned into two groups (RGSE and
placebo) using a computerized random numbers table. In-
dividuals responsible for grouping the subjects and the ex-
ecutive committee were unaware of group assignments. All
participants signed the informed consent and the study was
registered in ClinicalTrials.gov (NCT00713167).
The grape seed capsule used in this study was prepared at
the Drug Applied Research Center (Tabriz, Iran).
12
Capsule
ingredients were as follows: dicalcium phosphate, gelatin,
microcrystalline cellulose, and 100 mg of RGSE. Each
capsule contained the equivalent to 5–8 grape seeds. In an
analysis performed on this capsule, it contained at least 95%
of proanthocyanidins and 80% polyphenolic compounds.
Recruited individuals participated in a series of meetings
to get acquainted with the aim and significance of the study.
Participants were advised not to change their lifestyle,
general nutritional habits, and daily physical activity during
the study period. Patients were encouraged to continue
consuming any dietary supplementation or medication they
were using before the study, but were asked to stop con-
sumption of any grape product during the active phases.
The study design is illustrated in Figure 1. Initial blood
samples were taken after overnight fasting at the beginning
of the study. Specimens were centrifuged and the extracted
serum was stored at -94C. The RGSE group received
RGSE capsules (containing 100 mg RGSE) twice a day for 8
weeks, and the placebo group received similar-looking
capsules (filled with starch) for the same amount of time. A
second blood sample was collected at the end of the first
round. After an 8-week washout period, the groups were
crossed over. Two more blood samples were collected at the
beginning and end of the second round. Blood pressure,
BMI, and physical activity (number and length of activities
per week) were recorded at the time of sample collection.
Daily nutritional intake was recorded using a food frequency
questionnaire at the beginning and end of each round. The
questionnaires enabled the interviewer to calculate the
amount of each dietary intake category (protein, carbohy-
drate, fat, and fiber) as grams/day and categorize it on a scale
of 0 to 10.
Serum total cholesterol, TG, and high-density lipoprotein
cholesterol (HDL-C) were measured by an enzymatic col-
orimetric method with an automated chemical analyzer
(Abbott analyzer; Abbott Laboratories, Abbott Park, North
Chicago, IL, USA). The very low–density lipoprotein cho-
lesterol (VLDL-C) level was calculated by dividing TG by
five (TG/5), and low-density lipoprotein cholesterol (LDL-C)
was calculated with the Friedewald formula. Ox-LDL was
measured using an ELISA test (Mercodia Oxidized LDL
ELISA kit; Mercodia, Inc., Uppsala, Sweden).
Changes in dietary intake were analyzed by the Wilcoxon
signed ranks test. The paired samples t-test was employed to
compare before and after values in each group. Between-
group comparisons were carried out using the independent
samples t-test. Data were analyzed with SPSS software
(SPSS, Inc., Chicago, IL, USA) and P<.05 was considered
statistically significant.
FIG. 1. Schematic representation of
the study design.
256 RAZAVI ET AL.
Fifty-two patients were initially recruited. Four patients
failed to complete the first round because of lack of coop-
eration. From 48 patients (20 males, 28 females) finishing
the first round, 6 patients were lost to follow-up in the
washout period. All 42 remaining patients (18 males and 24
females) completed the second round, and analysis was
performed on a total of 90 cases. Values that were different
from the median by more than 1.5 interquartile ranges were
considered outliers, resulting in the exclusion of 15 cases
(Fig. 1).Ten subjects had unusual (very low or very high)
laboratory values due to improper sample handling or a
laboratory error. Lipid profile of the other five cases clearly
placed the subject in the severe hyperlipidemic range, both
before and after treatment.
The mean age of the patients was 48.22 ( –9.07 SD)
years. In spite of all precautions, the daily protein (P<.001)
and carbohydrate (P<.001) intake had increased signifi-
cantly during active phases, but mean daily fat and fiber
ingestion had no meaningful change.
HDL-C, LDL-C, VLDL-C, Ox-LDL, TG, total choles-
terol, weight, and systolic and diastolic blood pressure data
are shown in the Table 1.
The placebo and RGSE groups had no significant dif-
ference in any variable mean at the beginning of the study.
The mean weight was significantly increased after 8
weeks in both RGSE (P=.007) and placebo (P=.024)
groups. The RGSE group exhibited a significant decrease
in total cholesterol (-10.68 –26.76 mg/dL, P=.015),
LDL-C (-9.66 –23.92 mg/dL, P=.014), and Ox-LDL
(-5.47 –12.12 mg/dL, P=.008) (Table 1).
Comparing the mean change of variables after treatment
between groups, the RGSE group exhibited a greater de-
crease in Ox-LDL (-11.23 –16.21 mg/dL, P=.004) and
total cholesterol (-16.31 –30.75 mg/dL, P=.043) com-
pared to the placebo group (Table 1).
Our results show that RGSE can effectively reduce serum
total cholesterol, LDL-C, and Ox-LDL in individuals with
mild hyperlipidemia, but has no significant impact on TG,
HDL-C, and VLDL-C. Animal and in vitro studies have
found no toxic effect and few possible mutagenic effects of
the grape seed extract at very high doses (4–5 g/kg).
13,14
We
administered relatively smaller doses to our study subjects
and excluded patients with severe hyperlipidemia or other
underlying disease, further minimizing any risk of RGSE
consumption. We observed a meaningful increase in the
carbohydrate and protein consumption and weight in both
groups suggesting a possible confounding effect on serum
lipid profiles. Regression analysis did not find any of these
variables to be a predictor of lipid profiles or Ox-LDL.
French people consume more fat, exercise less, and
smoke more than other western societies, still their death
from cardiovascular disease is much lower; a phenomenon
known as the French paradox.
15
It is verified that polyphe-
nolic derivatives in red wine (e.g., oligomeric proantho-
cyanidins) are the origin of this chemoprotective effect.
15–17
Current data regarding the effect of RGSE and other
grape products on plasma lipid profiles are inconsistent.
Many studies have found RGSE to improve plasma lipid
profiles in animal models.
5,6
The proanthocyanidin-rich
grape seed extract had no effect on plasma lipid profiles in
cholesterol-fed rabbits, whereas it decreased the number of
Ox-LDL-positive foam cells in atherosclerotic lesions in the
aorta.
7
A few studies have investigated the lipid-lowering
and antioxidant activity of RGSE in humans. In a study
conducted on 24 heavy smoker subjects, Vigna et al. found
no significant change in plasma lipid profiles after 4 weeks
consumption of 75 mg RGSE twice daily; however, RGSE
decreased the susceptibility of LDL-C oxidation.
8
In another
study of 40 hypercholesterolemic individuals divided into
four groups, combined administration of niacin-bound
chromium and the grape seed proanthocyanidin extract de-
creased total cholesterol and LDL-C after 2 months.
9
With
previous studies in mind, we included individuals with mild
hyperlipidemia and only used RGSE as an intervention
against placebo to avoid any confounding factor in both the
population selection and in the treatment module. We also
Table 1. Variables in Red Grape Seed Extract and Placebo Groups
RGSE group Placebo group
Before After PBefore After PP
differencesa
Weight (kg) 67.81 68.33 .007
b
68.06 68.59 .024
b
.651
SBP (mmHg) 114.64 115.71 .524 114.22 116.09 .288 .211
DBP (mmHg) 70.24 72.62 .155 70.47 72.66 .232 .708
TG (mg/dL) 151.41 141.42 .060 174.07 173.89 .534 .380
Cholesterol (mg/dL) 228.03 216.97 .015
b
210.04 217.32 .121 .043
b
HDL-C (mg/dL) 50.46 51.37 .200 45.19 47.61 .485 .774
LDL-C (mg/dL) 147.28 137.32 .014
b
130.04 134.94 .280 .084
VLDL-C (mg/dL) 30.28 28.28 .060 34.81 34.78 .534 .380
Ox-LDL (mg/dL) 57.76 52.66 .008
b
53.45 59.21 .161 .004
b
a
Comparing mean change of variables between RGSE and placebo groups.
b
Statistically significant.
TG, triglyceride; RGSE, red grape seed extract; SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL-C, high-density lipoprotein cholesterol; LDL-C,
low-density lipoprotein cholesterol; VLDL-C, very low–density lipoprotein cholesterol; Ox-LDL, oxidized low-density lipoprotein cholesterol.
RGSE EFFECT ON LIPID PROFILE AND OX-LDL 257
increased the sample size and RGSE dose and extended the
treatment duration. The results of our study confirm the
lipid-lowering and antioxidant effects of RGSE.
Many studies have investigated the effects of RGSE on
LDL-C oxidation. In an in vitro model, the grape seed
showed a greater dose-dependent scavenging ability against
the superoxide anion and the hydroxyl radical compared to
vitamins C and E.
18
The effect of RGSE, red wine, and grape
juice on curtailing the oxidation of LDL-C has been verified
by many studies.
2,8,19
Our results confirm RGSE as a potent
antioxidant that can reduce serum Ox-LDL.
Despite promising results, there are some limitations in our
study. The sample size and treatment time were limited. We
used RGSE as a whole and did not distinguish between dif-
ferent contents of the grape seed extract and their possibly
different impacts on lipid profiles. Food frequency question-
naires were accurately designed, but further details on the
constituents of each food category, which could have helped in
additional analysis of confounding effects, were not recorded.
Considering the cardioprotective effect of grape seed
found in previous studies and with regard to our results, it
could be suggested that RGSE consumption has favorable
effects on serum lipid profile and decreases Ox-LDL, ulti-
mately decreasing the risk of atherosclerosis and cardio-
vascular disorders in mild hyperlipidemic individuals.
Long-term effects of RGSE on hyperlipidemic patients have
yet to be investigated.
ACKNOWLEDGMENTS
The authors appreciate the assistance of the physicians
and staff of Shahid Modarres Hospital cardiology clinics.
They also wish to thank all participating patients for their
cooperation.
AUTHOR DISCLOSURE STATEMENT
No competing financial interests exist.
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... According to the preclinical data, GSE was shown to have a positive impact on the lipid profile parameters of dyslipidemia and overweight participants and heavy smokers [192][193][194][195]. In fact, long-term treatment resulted in reduced total cholesterol [192][193][194][195], LDL [192][193][194] and triglyceride levels [192,195]. Moreover, a GSE-dependent reduction in the artherogenic index of plasma (AIP) was reported by Yousefi et al. [195]. ...
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  • Jan 2024
Background Progressive, involuntary weight and lean mass loss in cancer are linked to cachexia, a prevalent syndrome in gastrointestinal malignancies that impacts quality of life, survival and postoperative complications. Its pathophysiology is complex and believed to involve proinflammatory cytokine-mediated systemic inflammation resulting from tumor-host interaction, oxidative stress, abnormal metabolism and neuroendocrine changes. Therapeutic options for cachexia remain extremely limited, highlighting the need for clinical research targeting new interventions. Thus, this study primarily assesses the effects of grape-seed flour (GSF), rich in polyphenols and fibers, for attenuating perioperative weight loss in colorectal cancer. Methods This is a dual-center, triple-masked, placebo-controlled, parallel-group, phase II, randomized clinical trial designed to investigate GSF supplementation in subjects with pre- or cachexia associated with colorectal cancer during the perioperative period. Eighty-two participants will receive 8g of GSF or cornstarch (control) for 8 weeks. Assessments are scheduled around surgery: pre-intervention (4 weeks prior), day before, first week after, and post-intervention (4 weeks later). The primary endpoint is the difference in body weight mean change from baseline to week 8. The secondary endpoints describe the harms from 8-week supplementation and assess its superiority to improve body composition, post-surgical complications, quality of life, anorexia, fatigue, gastrointestinal symptoms, and handgrip strength. The study will also explore its effects on gut bacteria activity and composition, systemic inflammation, and muscle metabolism. Discussion The current trial addresses a gap within the field of cancer cachexia, specifically focusing on the potential role of a nutritional intervention during the acute treatment phase. GSF is expected to modulate inflammation and oxidative stress, both involved in muscle and intestinal dysfunction. The research findings hold substantial implications for enhancing the understanding about cachexia pathophysiology and may offer a new clinical approach to managing cachexia at a critical point in treatment, directly impacting clinical outcomes. Trial registration The Brazilian Registry of Clinical Trials (ReBEC), RBR-5p6nv8b; UTN: U1111-1285-9594. Prospectively registered on February 07, 2023.
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... vinifera, Vitaceae)-derived PACs can regulate lipid metabolism and significantly decreased the expression of pro-inflammatory cytokines, thus exerting hypolipidemic and potential anti-inflammatory effects in the liver [164]. The consumption of grape seed PACs has been related to lower oxidized low-density lipoprotein particles and LDL cholesterol [161,163], to improve dyslipidemia associated with a high-fat diet, mainly by repressing lipogenesis and VLDL assembly in the liver [162]. Furthermore, grape seed PACs exerted a pronounced effect on the cholesterol and triglyceride levels [165] and, by inhibiting oxidation of LDL, showed an antiatherosclerotic activity [166]. ...
Tackling the Future Pandemics: Broad-Spectrum Antiviral Agents (BSAAs) Based on A-Type Proanthocyanidins
Article
Full-text available
  • Nov 2022
  • MOLECULES
A-type proanthocyanidins (PAC-As) are plant-derived natural polyphenols that occur as oligomers or polymers of flavan-3-ol monomers, such as (+)-catechin and (−)-epicatechin, connected through an unusual double A linkage. PAC-As are present in leaves, seeds, flowers, bark, and fruits of many plants, and are thought to exert protective natural roles against microbial pathogens, insects, and herbivores. Consequently, when tested in isolation, PAC-As have shown several biological effects, through antioxidant, antibacterial, immunomodulatory, and antiviral activities. PAC-As have been observed in fact to inhibit replication of many different human viruses, and both enveloped and non-enveloped DNA and RNA viruses proved sensible to their inhibitory effect. Mechanistic studies revealed that PAC-As cause reduction of infectivity of viral particles they come in contact with, as a result of their propensity to interact with virion surface capsid proteins or envelope glycoproteins essential for viral attachment and entry. As viral infections and new virus outbreaks are a major public health concern, development of effective Broad-Spectrum Antiviral Agents (BSAAs) that can be rapidly deployable even against future emerging viruses is an urgent priority. This review summarizes the antiviral activities and mechanism of action of PAC-As, and their potential to be deployed as BSAAs against present and future viral infections.
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Winemaking: “With One Stone, Two Birds”? A Holistic Review of the Bio-Functional Compounds, Applications and Health Benefits of Wine and Wineries’ By-Products
Article
Full-text available
  • Sep 2023
The plethora of bio-functional compounds present in fermented alcoholic beverages like wine, as well as the valorisation of bioactives from wineries’/breweries’ by-products like grape pomace and grape seed, has gained significant interest in the functional foods sector. This functional beverage, wine, has always accompanied humanity, for religion or for health, especially in the Mediterranean, while the benefits of its moderate consumption were documented even by the Greek physician Hippocrates of Kos (460–370 BC). After a big gap, an outbreak of research on wine benefits has surfaced only since the 1990s, when the term “French paradox” was introduced to the US public during a CBS show, while recent evidence has outlined that the beneficial effects of wine consumption are derived by the synergisms of its bio-functional compounds and their digestion-derived metabolites. Within this article, the proposed health benefits of moderate wine consumption, as a functional component of a balanced diet (i.e., the Mediterranean diet) against inflammation-related chronic disorders, is thoroughly reviewed. The various bio-functional compounds of both wine and wineries’ by-products, such as their bioactive phenolics, unsaturated fatty acids, polar lipids and dietary fibres, and their functional antioxidant, anti-inflammatory and antithrombotic health-promoting properties, are also thoroughly evaluated. The mechanisms of action and synergism, by which the health benefits are elicited, are also explored. Functional properties of non-alcoholic wine products are also introduced. Emphasis is also given to applications of wineries’ by-products bioactives, as ingredients of bio-functional foods, supplements and nutraceuticals. Limitations and future perspectives for this popular functional alcoholic beverage (wine) and its rich in bioactives by-products are also addressed.
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The Effect of Grape Seed Extract on Lipid Profile in Diabetic Mice
Article
Full-text available
  • Jul 2023
The aim of this work is to evaluate the role of Grape Seed extracts (GSE) from three grape cultivars (Ahmer, Halawani, and Kamali) grown in Iraq as well as pomace on lipid profile in diabetic mice. Fifty adult female mice were divided into five groups. Negative control (untreatment), positive control (treated) diabetic, and diabetic mice treated with GSE. After six weeks; serum and liver tissue homogenate parameters were evaluated. HPLC results showed that Ahmer (red grape seeds) has highest concentration of proanthocyanidins polymers catechine, procyanidin, and epicatechine (796, 170, and 244) μg/g, respectively For that it was chosen for mice dosage, while the lowest amounts were in pomace 489, 99, and 143 μg/g, respectively. Oral dose of grape seed natural extract (600 mg/kg/day) reduced the level of lipid profile: TC, TG, LDL, and VLDL, (106.83±2.13, 84.66±4.27,13.83±1.16 and 21.33±1.21) respectively, except HDL which respectively was increased to 76.33±1.03. GSE were normalized the elevated levels of kidneys and liver functions. Similarly, Liver histological analysis shows that GSE groups exhibited morphology near to that of the control group.
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Medicinal Herbs as an Alternative Treatment in the Management of Hyperlipidemia
Article
Full-text available
  • Jun 2023
The medical disorder known as hyperlipidemia is characterized by unusually high amount of lipids in the blood (fatty substances). This illness is also associated with being overweight. Even though hypolipidemic drugs are commonly used to treat cardiovascular diseases and stroke, there is a possibility that they may cause undesirable side effects. Many different medicinal plants have been successfully utilized in the treatment of various conditions in India. The treatment of hyperlipidemia was the primary focus of this investigation into the therapeutic properties of a variety of plants.
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Proanthocyanidin prevents myocardial ischemic injury in adult rats
Article
Full-text available
  • Nov 2011
  • MED SCI MONITOR
Proanthocyanidin is a bioflavonoid known to have protective effect against oxidative injury. We investigated the cardioprotective effect of proanthocyanidin. Thirty-two Rattus Norvegicus rats were categorized equally as the control group (CG), proanthocyanidin group (PCG), ischemia group (IG) and proanthocyanidin-treated group (PCT). Rats in CG and IG were fed standard rat food and PCG and PCT were fed standard rat food plus proanthocyanidin (100 mg/kg/day twice a day by oral gavage) for 3 weeks. In CG and PCG the myocardial samples were prepared immediately, and in IG and PCT hearts were placed in transport solution and kept at 4°C for 5 hours, then prepared for evaluation. Malondialdehyde (MDA) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities were measured. MDA levels were significantly higher in IG and PCT than in CG and PCG. The activity of SOD was significantly lower in IG and higher in PCG than in the other groups. The activity of GPx was significantly lower in IG than in the other groups. The activities of CAT were significantly lower in IG and PCT than in the other groups and were significantly lower in IG than PCT. Histopathologic evaluation revealed normal findings in CG and PCG. While ischemic injury was observed in IG, the content of muscle fibers was better preserved in PCT. Proanthocyanidin may have a protective effect on myocardial ischemic injury.
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Protective Effect of Grape Seed Extract on Gentamicin-Induced Acute Kidney Injury
Article
Full-text available
  • Oct 2010
INTRODUCTION. This study was designed to determine the protective effect of red grape seed extract (RGSE) on gentamicin-induced nephrotoxicity in rats. MATERIALS AND METHODS. Thirty male Wistar rats were divided into 3 groups to receive RGSE, for 60 days followed by intraperitoneal injection of saline solution (as placebo) for 8 days (group 1); RGSE followed by gentamicin for 8 days (group 2); and gentamicin without pre-medication of RGSE (group 3). Oral RGSE, 40 mg/kg/d, and intraperitoneal injection of gentamicin, 100 mg/kg/d, were administered in these groups of rats. Blood and urine samples were collected on days 0 and 68 of the study. Then, the kidneys were removed for pathologic examination. RESULTS. On day 68, serum creatinine and blood urea nitrogen concentrations were highest in group 3, which was significantly higher than in group 1 (P = .001 and P = .004, respectively), while slightly higher than in group 2 (P = .30 and P = .50, respectively). Fractional excretion of sodium was not significantly different between the three groups. Histopathological evaluation showed that rats in group 3 had significantly higher degrees of severe acute tubular necrosis and interstitial mononuclear cell infiltration than the rats in groups 1 and 2 (P < .001). CONCLUSIONS. This animal study suggests that pretreatment with RGSE protects against gentamicin-induced acute kidney injury as evident on tissue histology. However, this was not accompanied with significant improvement in biochemical markers of kidney injury.
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Grape seed proanthocyanidins correct dyslipemia associated with a high-fat diet in rats and repress genes controlling lipogenesis and VLDL assembling in liver
Article
Full-text available
  • Aug 2009
  • INT J OBESITY
To determine whether proanthocyanidins can protect against dyslipidemia induced by a high-fat diet (HFD) and to address the mechanisms that underlie this hypolipidemic effect. Female Wistar rats were fed on a HFD for 13 weeks. They were divided into two groups, one of which was treated with a grape seed proanthocyanidin extract (25 mg kg(-1) of body weight) for 10 days. Plasma and liver lipids were measured by colorimetric and gravimetric analysis. Liver, muscle and adipose tissue were used to study the expression of genes involved in the synthesis and oxidation of fatty acids and lipoprotein homeostasis by real-time RT-PCR. The administration of proanthocyanidins normalized plasma triglyceride and LDL-cholesterol (both parameters significantly increased with the HFD) but tended to decrease hypercholesterolemia and fatty liver. Gene expression analyses revealed that proanthocyanidins repressed both the expression of hepatic key regulators of lipogenesis and very low density lipoprotein (VLDL) assembling such as SREBP1, MTP and DGAT2, all of which were overexpressed by the HFD. These findings indicate that natural proanthocyanidins improve dyslipidemia associated with HFDs, mainly by repressing lipogenesis and VLDL assembly in the liver, and support the idea that they are powerful agents for preventing and treating lipid altered metabolic states.
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Wine, alcohol, platelets, and the French paradox for coronary heart disease
Article
  • Jun 1992
In most countries, high intake of saturated fat is positively related to high mortality from coronary heart disease (CHD). However, the situation in France is paradoxical in that there is high intake of saturated fat but low mortality from CHD. This paradox may be attributable in part to high wine consumption. Epidemiological studies indicate that consumption of alcohol at the level of intake in France (20-30 g per day) can reduce risk of CHD by at least 40%. Alcohol is believed to protect from CHD by preventing atherosclerosis through the action of high-density-lipoprotein cholesterol, but serum concentrations of this factor are no higher in France than in other countries. Re-examination of previous results suggests that, in the main, moderate alcohol intake does not prevent CHD through an effect on atherosclerosis, but rather through a haemostatic mechanism. Data from Caerphilly, Wales, show that platelet aggregation, which is related to CHD, is inhibited significantly by alcohol at levels of intake associated with reduced risk of CHD. Inhibition of platelet reactivity by wine (alcohol) may be one explanation for protection from CHD in France, since pilot studies have shown that platelet reactivity is lower in France than in Scotland.
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Atherosclerosis – An Inflammatory Disease
Article
  • May 1996
The advanced lesions of atherosclerosis represent the culmination of a specialized form of chronic inflammation followed by a fibroproliferative process that takes place within the intima of the affected artery. Proliferation of smooth muscle cells and generation of connective tissue occur. Proliferation results from interactions between arterial smooth muscle, monocyte-derived macrophages, T lymphocytes, and endothelium. The initial lesion of atherosclerosis, the fatty streak, begins as an accumulation of monocytederived macrophages and T lymphocytes, which adhere and migrate into the intima of the affected artery. Smooth muscle cells, which are present in the intima or which migrate into the intima from the media, then replicate. Monocyte-derived macrophages and T cells also replicate during lesion formation and progression due to the production of cytokines and growth-regulatory molecules. These molecules determine whether there is proliferation and lesion progression or inhibition of proliferation and lesion regression. Several growthregulatory molecules may play critical roles in this process, including platelet-derived growth factor (PGDF), transforming growth factor beta, fibroblast growth factor, heparinbinding epidermal growth factor-like growth factor, and others. PDGF may be one of the principal components in this process because protein containing the PDGF B-chain has been demonstrated within activated lesion macrophages during every phase of atherogenesis. The presence of this growth factor and its receptors on lesion smooth muscle cells creates opportunities for smooth muscle chemotaxis and replication. Smooth muscle proliferation depends upon a series of complex signals based upon cellular interactions in the local microenvironment of the artery. The intracellular signalling pathways for mitogenesis versus chemotaxis are being investigated for smooth muscle. The roles of the cytokines and growth-regulatory peptides involved in these cellular interactions represent critical points of departure for intervention and the development of new diagnostic methods. In addition, magnetic resonance imaging has been developed to demonstrate the fine structure of lesions of atherosclerosis in peripheral arteries not subject to cardiac motion. This noninvasive methodology holds great promise for the future of these approaches.
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Low doses of grape seed procyanidins reduce adiposity and improve the plasma lipid profile in hamsters
Article
  • May 2012
  • INT J OBESITY
Objective: Procyanidins are polyphenolic compounds with beneficial effects on health in relation to cardiovascular disease and metabolic syndrome. In this study, we evaluated the potential beneficial effects of low doses of a grape seed procyanidin extract (GSPE) on body weight and fat deposition. Design: Four groups of hamsters were fed either a standard diet (STD) or a high-fat diet (HFD) for 30 days and supplemented with either GSPE at 25 mg per kg of body weight per day (STD-GSPE and HFD-GSPE groups) or vehicle (STD and HFD groups) during the last 15 days of the study. Results: A significant decrease in body weight gain was observed in both GSPE-treated animals at the end of the experiment. GSPE treatment significantly reduced the adiposity index and the weight of all the white adipose tissue depots studied (retroperitoneal (RWAT), mesenteric (MWAT), epididymal (EWAT) and inguinal (IWAT)) in both GSPE-treated groups. GSPE administration reversed the increase in plasma phospholipids induced by the HFD feeding. In the RWAT, GSPE treatment increased the mRNA expression of genes related to β-oxidation and the glycerolipid/free fatty acid (GL/FFA) cycle, mainly in HFD-GSPE animals. In the MWAT, the effects of GSPE at the transcriptional level were not as evident as in the RWAT. Moreover, GSPE treatment induced heparin-releasable lipoprotein lipase activity in the RWAT and MWAT depots. The alterations in the lipid metabolic pathways induced by GSPE were accompanied by lower FFA levels in the plasma and decreased lipid and triglyceride accumulation in the MWAT. Conclusion: The use of GSPE at low doses protects against fat accumulation and improves the plasma lipid profile in hamsters. We suggest that GSPE exerts these effects in part through the activation of both β-oxidation and the GL/FFA cycle, mainly in the RWAT.
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Oxidized LDL, LOX-1 and atherosclerosis
Article
  • Sep 2011
  • CARDIOVASC DRUG THER
An elevated level of low density lipoprotein (LDL) cholesterol constitutes a major risk factor for genesis of atherosclerosis. Ox-LDL plays a more important role in the genesis and progression of atherosclerosis than the native LDL. Ox-LDL leads to endothelial dysfunction leading to expression of adhesion molecules and recruitment of monocyte in subendothelial space. Ox-LDL is taken up by macrophages via scavenger receptors, such as SR-A1, SR-A2 and LOX-1. Lately, LOX-1, a type II membrane protein receptor of ox-LDL, has gained much importance in relation to effects of ox-LDL on endothelial biology. Endothelial cells primarily express LOX-1 as receptor for ox-LDL and ox-LDL has been shown to upregulate expression of LOX-1. In addition, ox-LDL promotes the growth and migration of smooth muscle cells, monocytes/macrophages and fibroblasts. In this review we discuss the role of ox-LDL and LOX-1 in genesis and progression of atherosclerosis.
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Toxicology evaluation of a procyanidin-rich extract from grape skins and seeds
Article
  • Mar 2011
The procyanidin-rich extract from grape seeds and skins (GSSE) has antioxidant properties which may have cardioprotective effects. Since it might be interesting to incorporate this extract into a functional food, toxicological tests need to be made to determine how safe it is. In this study we carried out a limit test to determine the acute oral toxicity and the lethal dose 50 (LD50) and some genotoxicity tests of the extract in rats. The LD50 was higher than 5000 mg/kg. Doses of up to 2000 mg/kg showed no increase in micronucleated erythrocytes 72 h after treatment. The bacterial reverse mutation test showed that the extract was weakly mutagenic to the dose of 5 mg/plate and 19.5 and 9.7 μg/ml of GSSE did not show significant differences in the frequency of aberrant metaphases in relation to negative controls. Our results indicated slight mutagenicity under the study conditions, so further studies should be conducted at lower doses to demonstrate that this extract is not toxic.
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Renaud, S. & De Lorgeril, M. Wine, alcohol, platelets and the French paradox for coronary heart disease. Lancet 339, 1523-1526
Article
  • Jul 1992
In most countries, high intake of saturated fat is positively related to high mortality from coronary heart disease (CHD). However, the situation in France is paradoxical in that there is high intake of saturated fat but low mortality from CHD. This paradox may be attributable in part to high wine consumption. Epidemiological studies indicate that consumption of alcohol at the level of intake in France (20-30 g per day) can reduce risk of CHD by at least 40%. Alcohol is believed to protect from CHD by preventing atherosclerosis through the action of high-density-lipoprotein cholesterol, but serum concentrations of this factor are no higher in France than in other countries. Re-examination of previous results suggests that, in the main, moderate alcohol intake does not prevent CHD through an effect on atherosclerosis, but rather through a haemostatic mechanism. Data from Caerphilly, Wales, show that platelet aggregation, which is related to CHD, is inhibited significantly by alcohol at levels of intake associated with reduced risk of CHD. Inhibition of platelet reactivity by wine (alcohol) may be one explanation for protection from CHD in France, since pilot studies have shown that platelet reactivity is lower in France than in Scotland.
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Oxygen free radical scavenging abilities of vitamin C and E, and a grape seed proanthocyanidin extract in vitro
Article
  • Mar 1997
  • Res Comm Mol Pathol Pharmacol
Proanthocyanidins, a group of polyphenolic bioflavonoids, have been reported to exhibit a wide range of biological, pharmacological and chemoprotective properties against oxygen free radicals. We have assessed the concentration-dependent oxygen free radical scavenging abilities of a grape seed proanthocyanidin extract (GSPE), vitamin C and vitamin E succinate (VES) as well as superoxide dismutase, catalase and mannitol against biochemically generated superoxide anion and hydroxyl radical using a chemiluminescence assay and cytochrome c reduction. A concentration-dependent inhibition was demonstrated by GSPE. At a 100 mg/l concentration, GSPE exhibited 78-81% inhibition of superoxide anion and hydroxyl radical. Under similar conditions, vitamin C inhibited these two oxygen free radicals by approximately 12-19%, while VES inhibited the two radicals by 36-44%. The combination of superoxide dismutase and catalase inhibited superoxide anion by approximately 83%, while mannitol resulted in an 87% inhibition of hydroxyl radical. The results demonstrate that GSPE is a more potent scavenger of oxygen free radicals as compared to vitamin C and VES.
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