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Current
Pharmaceutical Biotechnology
ISSN: 1389-2010
Current Pharmaceutical Biotechnology
Volume 11, Number 8, December 2010
Contents
Natural Products for the Healthy Heart
Guest Editor: Dipak K. Das
Editorial:
Pp. 792-793
Natural Products in Regression and Slowing of Progression
of Atherosclerosis Pp. 794-800
K. Prasad
[Abstract] [Purchase
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Assessment of Antioxidant Capacity of Natural
Products Pp. 801-809
E. Niki
[Abstract]
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Resveratrol: A Multifunctional Cytoprotective
Molecule Pp. 810-818
B. Juhasz, B. Varga, R. Gesztelyi, A. Kemeny-Beke,
J. Zsuga and A. Tosaki
[Abstract] [Purchase
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Role of Antioxidants in Redox Regulation of Diabetic
Cardiovascular Complications Pp. 819-836
B. Turan
[Abstract] [Purchase
Article]
Hypertension, Nitric Oxide, Oxidants, and Dietary
Plant Polyphenols Pp. 837-848
M. Galleano, O. Pechanova and C.G. Fraga
[Abstract] [Purchase
Article]
Amelioration of Myocardial Ischemic Reperfusion
Injury with Calendula officinalis Pp. 849-854
D. Ray, S. Mukherjee, P. Braga, M. Falchi,
A. Bertelli and D.K. Das
[Abstract] [Purchase
Article]
Terminalia arjuna in Cardiovascular Diseases:
Making the Transition from Traditional to Modern Medicine
in India Pp. 855-860
S.K. Maulik and C.K. Katiyar
[Abstract] [Purchase
Article]
Cardiac Oxidative Stress and Inflammation are
Similar in SAMP8 and SAMR1 Mice and Unaltered by Curcumin
and Ginkgo biloba Extract Intake Pp. 861-867
C. Schiborr, G.P. Eckert, J. Weißenberger,
W.E. Müller, D. Schwamm, T. Grune, G. Rimbach and
J. Frank
[Abstract] [Purchase
Article]
Protective Effect of Natural Antioxidants on Heart
Against Ischemia-Reperfusion Damage Pp. 868-874
Y. Zhao and B. Zhao
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Article]
Squalene as Novel Food Factor Pp. 875-880
H.N. Bhilwade, T. Naoto, N. Hiroshi and
T. Konishi
[Abstract] [Purchase
Article]
Green Tea Attenuates Cardiovascular Remodelling
and Metabolic Symptoms in High Carbohydrate-Fed Rats Pp.
881-886
C. Rickman, A. Iyer, V. Chan and L.
Brown
[Abstract] [Purchase
Article]
Flavonoid Rich Fraction of Dioscorea bulbifera
Linn. (Yam) Enhances Mitochondrial Enzymes and Antioxidant
Status, Thereby Protects Heart from Isoproterenol Induced
Myocardial Infarction Pp. 887-894
K.S. Jayachandran, H.R. Vasanthi and
G.V. Rajamanickam
[Abstract] [Purchase
Article]
Antiapoptotic Effect of Novel Compound from Herba
leonuri- Leonurine (SCM-198): A Mechanism Through Inhibition
of Mitochondria Dysfunction in H9c2 Cells Pp. 895-905
X.H. Liu, L.L. Pan, Q.H. Gong and Y.Z.
Zhu
[Abstract] [Purchase
Article]
Restoration of Cardiomyocyte Function in Streptozotocin
Induced Diabetic Rats after Treatment with Vanadate in a Tea
Decoction Pp. 906-910
T.A. Clark, T.G. Maddaford, P.S. Tappia, C.E.
Heyliger, P.K. Ganguly and G.N. Pierce
[Abstract] [Purchase
Article]
Diet and Heart Health: Moderate Wine Drinking
Strengthens the Cardioprotective Effects of Fish Consumption
Pp. 911-921
J. de Leiris, S. Besse and F. Boucher
[Abstract] [Purchase
Article]
Abstracts
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Natural Products in Regression and Slowing of Progression
of Atherosclerosis
K. Prasad
Many natural products, including vitamin E, garlic, purpurogallin,
flaxseed and its components [secoisolariciresinol diglucoside
(SDG) and flax lignan complex (FLC)] and resveratrol have
been reported to suppress hypercholesterolemic atherosclerosis.
It is known that all of the drugs that suppress the development
of atherosclerosis do not regress and/or slow the progression
of atherosclerosis. To be of potential benefit in patients
with established atherosclerosis, a drug should produce regression
and/or slow the progression of atherosclerosis. In this review,
the effects of vitamin E, SDG and FLC in the regression and
slowing of progression of hypercholesterolemic atherosclerosis
and their mechanisms have been described. The effectiveness
of vitamin E in patients with established coronary disease
is very controversial. However, in experimental animal controlled
studies, vitamin E does not regress or slow the progression
of hypercholesterolemic atherosclerosis. The mechanisms of
the ineffectiveness of vitamin E in regression and slowing
of progression of atherosclerosis have been discussed. SDG
is effective in slowing the progression of atherosclerosis
and partially effective in regression of hypercholesterolemic
atherosclerosis. These effects are associated with reduction
in oxidative stress. FLC does not regress hypercholesterolemic
atherosclerosis but slows the progression of hypercholesterolemic
atherosclerosis. Slowing of progression is associated with
reduction on oxidative stress. In conclusion, vitamin E does
not regress or slow the progression of established atherosclerosis.
SDG slows the progression and regresses established atherosclerosis.
FLC does not regress but slows the progression of established
atherosclerosis.
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Assessment of Antioxidant Capacity of Natural Products
E. Niki
It is now widely accepted that oxidative stress induced
by reactive oxygen and nitrogen species is involved in the
pathogenesis of various diseases such as atherosclerosis and
cardiovascular disease and consequently the role of antioxidants
in the prevention and treatment of diseases has received much
attention of scientists, clinicians and general public. However,
most of the large clinical intervention trials of antioxidants
and meta-analysis of the data from these large studies do
not show beneficial evidence with regard to cardiovascular
outcomes. In order to understand the role of antioxidants,
it is essential to elucidate the action and capacity of antioxidants.
In this article, the assessment of antioxidant capacity is
reviewed and the methods for assessment of natural antioxidant
capacity are discussed.
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Resveratrol: A Multifunctional Cytoprotective Molecule
B. Juhasz, B. Varga, R. Gesztelyi, A. Kemeny-Beke, J.
Zsuga and
A. Tosaki
Several recent studies have shown the protective effects
of resveratrol in various experimental conditions and pathological
animal models. Clinical studies also indicate the beneficial
effects of resveratrol in different human diseases. Resveratrol
produces a cascade against of events from the initial death-provoking
signal, DNA fragmentation, and cell death. Researchers recognized
the beneficial effect of resveratrol, as an important component,
of the overall injury that occurs in various disorders such
as oxidative stress, myocardial injury, anticancer activity,
antidiabetic activity, and antihypercholesterolemic effects.
Many mechanisms have been proposed for the initiation
of protective effects of resveratrol in various pathological
events, and considerable evidence exists to indicate that
many mediators are involved in the resveratrol-induced protection.
The present review focuses on the history, and the beneficial
effects and mechanisms of resveratrol in oxidative stress,
myocardial injury, anticancer-, antidiabetic- and antihypercholesterolemic
activities, and discusses those therapeutic tools, which warrant
becoming clinically important.
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Role of Antioxidants in Redox Regulation of Diabetic Cardiovascular
Complications
B. Turan
Cardiovascular dysfunction is leading cause for the mortality
of diabetic individuals, in part due to a specific cardiomyopathy,
and due to altered endothelial dependent/independent vascular
reactivity. Cardiovascular complications result from multiple
parameters including glucotoxicity, lipotoxicity, fibrosis
and mitochondrial uncoupling. Oxidative stress arises from
an imbalance between the production of reactive oxygen and
nitrogen species (ROS and RNS) and the capability of biological
system to readily detoxify reactive intermediates. Several
studies have reported beneficial effects of a therapy with
antioxidant agents, including trace elements and other antioxidants,
against the cardiovascular system dysfunction due to the diabetes.
Antioxidants act through different mechanisms to prevent oxidant-induced
cell damages acting either directly or indirectly. They can
reduce the generation of ROS, scavenge ROS, or interfere with
ROS-induced alterations. Modulating mitochondrial activity
is an important possibility to control ROS production. Hence,
the use of PPARα
agonist to reduce fatty acid oxidation and of trace elements
such as selenium as antioxidant and other antioxidants such
as vitamins E and C, contribute to the prevention of diabetes-induced
cardiovascular dysfunction. The paradigm that, inhibiting
the overproduction of superoxides and peroxides would prevent
cardiac dysfunction in diabetes has been difficult to verify
using conventional antioxidants like vitamins E and C, that
led to use of catalytic antioxidants such as SOD/CAT mimetics.
Hence, well-tuned, balanced and responsive antioxidant defence
systems are vital for proper prevention against diabetic damage.
Myocardial cell death is observed in the hearts of diabetic
patients and animal models; however, its importance in the
development of diabetic cardiomyopathy is not completely understood.
This review aims to summarize our present knowledge on various
strategies to control oxidative stress and antagonize cardiovascular
dysfunction during diabetes. In here, I consider aspects of
redox signaling in the cardiovascular system, focusing on
the molecular basis of redox sensing by proteins and the array
of post-translational oxidative modifications that can occur.
In addition, I discuss studies identify redox-sensitive cardiac
proteins, as well as those assessing redox signalling in cardiovascular
disease.
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Hypertension, Nitric Oxide, Oxidants, and Dietary Plant Polyphenols
M. Galleano, O. Pechanova and C.G. Fraga
Fruits and vegetables are key foods whose high ingestion
is associated with the improvement of numerous pathological
conditions, including hypertension. Such health promoting
actions have been increasingly ascribed to the antioxidant
characteristics of different polyphenols in fruits and vegetables.
Consequently, based on this assumption, many beverages and
foods rich in polyphenols, grape, tea, cocoa, and soy products
and many of their chemical constituents purified, are being
studied both, as antioxidants and antihypertensive agents.
This paper reviews the current evidence linking high polyphenol
consumption with reductions in blood pressure. Basic chemical
aspects of flavanols, flavonols, isoflavones and stilbenes,
as possible responsible for the observed effects of those
foods on blood pressure are included. Human intervention studies
by using grapes and wine, cocoa and chocolate, black and green
tea, soy products, and purified compounds ((+)-catequin, quercetin,
(-)-epigallocatechin gallate) are summarized. The discussed
hypothesis, strongly supported by experimental data in animals,
is that by regulating nitric oxide bioavailability, polyphenols
present in fruits and vegetables affect endothelial function
and as a consequence, blood pressure. Even when data are not
definitive and many questions remain open, the whole evidence
is encouraging to start considering diets that can provide
benefits to hypertensive subjects, and those benefits will
be more significant in people that do not have controlled
his/her elevated blood pressure.
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Amelioration of Myocardial Ischemic Reperfusion Injury with
Calendula officinalis
D. Ray, S. Mukherjee, P. Braga, M. Falchi, A. Bertelli
and D.K. Das
Calendula officinalis of family Asteraceae,
also known as marigold, has been widely used from time immemorial
in Indian and Arabic cultures as an anti-inflammatory agent
to treat minor skin wound and infections, burns, bee stings,
sunburn and cancer. At a relatively high dose, calendula can
lower blood pressure and cholesterol. Since inflammatory responses
are behind many cardiac diseases, we sought to evaluate if
calendula could be cardioprotective against ischemic heart
disease Two groups of hearts were used: the treated rat hearts
were perfused with calendula solution at 50 mM in KHB buffer
(in mM: sodium chloride 118, potassium chloride 4.7, calcium
chloride 1.7, sodium bicarbonate 25, potassium biphosphate
0.36, magnesium sulfate 1.2, and glucose 10) for 15 min prior
to subjecting the heart to ischemia, while the control group
was perfused with the buffer only. Calendula achived cardioprotection
by stimulating left ventricular developed pressure and aortic
flow as well as by reducing myocardial infarct size and cardiomyocyte
apoptosis. Cardioprotection appears to be achieved by changing
ischemia reperfusion-mediated death signal into a survival
signal by modulating antioxidant and anti-inflammatory pathways
as evidenced by the activation of Akt and Bcl2 and depression
of TNFα.
The results further strengthen the concept of using natural
products in degenerative diseases like ischemic heart diseas.
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Terminalia arjuna in Cardiovascular Diseases: Making
the Transition from Traditional to Modern Medicine in India
S.K. Maulik and C.K. Katiyar
The stem bark of Terminalia arjuna (Roxb.) is
used by the Ayurvedic physicians in India for the treatment
of various cardiovascular diseases, collectively referred
to as hritroga. It has been extensively studied in
animal models to demonstrate cardioprotective properties,
ranging from positive inotropic- , hypolipdemic-, coronary
vasodilatory- and antioxidant effects to induction of stress
protein in heart. Various bioactive compounds, like triterpinoids,
tannins, flavonoids and minerals have been isolated from the
stem bark. A number of clinical studies have also reported
its beneficial effects in patients of chronic stable angina,
endothelial dysfunction, heart failure and even ischemic mitral
regurgitation. However, there are some identified lacunae,
like standardisation of the ‘drug’, toxicity studies
along with pharmacological interactions with other drugs and
large multicentre randomized clinical trials, before its use
by modern medicine is acceptable.
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Cardiac Oxidative Stress and Inflammation are Similar
in SAMP8 and SAMR1 Mice and Unaltered by Curcumin and Ginkgo
biloba Extract Intake
C. Schiborr, G.P. Eckert, J. Weißenberger, W.E.
Müller, D. Schwamm, T. Grune, G. Rimbach and
J. Frank
Chronic inflammation and oxidative stress increase with
advancing age and appear to be involved in the pathogenesis
of coronary heart disease, the leading cause of death worldwide.
There is a need for animal models that reflect the increases
in pro-inflammatory cytokines and oxidative damage observed
during aging in humans. We therefore aimed to investigate
the suitability of the fast-aging senescence-accelerated mouse-prone
8 (SAMP8) strain and its normally aging control senescence-accelerated
mouse-resistant 1 (SAMR1) to study the age-dependent changes
in cytokines, oxidative damage and antioxidants in the heart.
To this end, 2-months-old male SAMR1 and SAMP8 mice were fed
a Western type diet (control groups) for 5 months. Two groups
of SAMP8 mice were simultaneously fed identical diets fortified
with 0.5 g curcumin or 1.0 g Ginkgo biloba extract
EGb 761®
per kg diet. Heart tissue homogenates were analysed for protein
carbonyls, glutathione, glutathione disulfide, methionine,
cysteine and uric acid as well as the cytokines tumor-necrosis
factor-α,
interleukin-1β,
interleukin-6, and monocyte chemoattractant protein‑1.
Neither the strain (SAMR1 or SAMP8) nor antioxidant intake
(curcumin or EGb 761®)
affected the concentrations of the measured parameters. In
conclusion, our data do not support the suitability of the
SAMP8 and SAMR1 strains as a model to study age-related changes
in pro-inflammatory cytokines and oxidative stress parameters
in the heart.
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Protective Effect of Natural Antioxidants on Heart Against
Ischemia-Reperfusion Damage
Y. Zhao and B. Zhao
The incidence and mortality of heart disease are the
highest among all diseases all over the world, and are still
increasing with a world wide rise in living standards. To
find effective treatments for prevention and curing heart
disease, it is important to understand the mechanisms behind
the cause and the development of the disease. Increasing evidences
have shown that reactive oxygen species (ROS) and reactive
nitrogen species (RNS) play important roles in the initiation
and progression of heart disease. The potential of using antioxidants,
especially the natural antioxidants, in preventing and curing
the disease has attracted enormous interest. In this paper
we reviewed the progress made in understanding the oxidative
stress caused by myocardial ischemia-reperfusion and the cardioprotective
effect of natural antioxidants against ischemia-reperfusion
injury.
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Squalene as Novel Food Factor
H.N. Bhilwade, T. Naoto, N. Hiroshi and T. Konishi
Currently, health beneficial roles of natural products
attract much attention and diverse functional ingredients
have been extensively studied their preventive effect in many
diseases such as cardiovascular diseases and cancer. Squalene
is one of those examples. It distributes in nature from plant
to animal but extraordinarily concentrated in the liver of
certain species of shark (Squalidae family) as it was first
identified as a healing substance in the shark liver oil.
It is now well-known that squalene is the physiological substance
functioning in animal as the precursor of cholesterol biosynthesis.
On the other hand, it has long history of using as an attractive
resource for functional food, supplement or even pharmaceutics
because it has unique physical property and wide variety of
physiological functions such as anticancer and anti-hyper
cholesterolemia. The antioxidant and oxygen carrying properties
of squalene predicts its potential in preventing cardiovascular
disease. We reviewed recent progress in functional studies
of squalene both in vitro and in vivo models.
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Green Tea Attenuates Cardiovascular Remodelling and Metabolic
Symptoms in High Carbohydrate-Fed Rats
C. Rickman, A. Iyer, V. Chan and L. Brown
Excess carbohydrate in the diet may initiate a chronic
state of oxidative stress exacerbating the clinical and biochemical
symptoms of diet-induced type 2 diabetes, especially glucose
intolerance, lipid abnormalities and cardiovascular complications.
This study has tested whether green tea, rich in antioxidants,
improves both cardiovascular symptoms and glucose intolerance
and also reduces oxidative stress in rats fed a high carbohydrate
diet. Male 8 week old Wistar rats were fed a diet including
fructose and condensed milk (each 40%) for 16 weeks (112 days);
control rats were fed corn starch. Green tea-containing food
was started from day 1 for the prevention protocol and from
day 56 for the reversal protocol. High carbohydrate diet-fed
rats showed glucose intolerance, hypertension, mild left ventricular
hypertrophy, approximate doubling of cardiac interstitial
and perivascular collagen deposition, increased passive diastolic
stiffness and increased plasma malondialdehyde concentrations.
Administration of green tea to high carbohydrate diet-fed
rats prevented and reversed glucose intolerance and the increased
systolic blood pressure, left ventricular wet weight, interstitial
collagen and passive diastolic stiffness. Plasma malondialdehyde
concentrations were also normalized. In summary, treatment
with green tea both prevented and reversed the cardiovascular
remodeling and metabolic changes seen in high carbohydrate-fed
rats suggesting a chronic state of oxidative stress plays
a key role in the symptom initiation and progression. Further,
green tea may be a useful complementary therapy in diet induced
type 2 diabetes.
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Flavonoid Rich Fraction of Dioscorea bulbifera
Linn. (Yam) Enhances Mitochondrial Enzymes and Antioxidant
Status, Thereby Protects Heart from Isoproterenol Induced
Myocardial Infarction
K.S. Jayachandran, H.R. Vasanthi and G.V. Rajamanickam
With recent advances in nutrition sciences, natural products
and health-promoting foods have received extensive attention
from both health professionals and the common population.
The flavonoid rich fraction (FRF) of Dioscorea bulbifera
Linn. has a strong free radical scavenging activity. FRF (150
mg/kg) when intervened for a period of 35 days prior to isoproterenol
(ISO) challenge to rats maintained the creatine kinase –
MB (CK-MB) activity in serum without elevation. Alterations
in the antioxidant status in the mitochondria were recognized
in the heart tissue of ISO induced rats. ISO induced rats
pretreated with FRF (150 mg/kg) ameliorated the lipid peroxidation
and thereby enhanced the antioxidant status as evidenced by
the increase in the reduced glutathione (GSH) content and
the activity of antioxidant enzymes. Moreover, the tricarboxylic
acid cycle enzymes such isocitrate dehydrogenase (ICDH), succinate
dehydrogenase (SDH), malate dehydrogenase (MDH) and α-ketoglutarate
dehydrogenase (α-KGDH),
which were found decreased in the ISO induced rats showed
an enhanced activity in FRF (150 mg/kg) pretreated rats. The
activity of NADH dehydrogenase and cytochrome- C-oxidase,
the enzymes which transfer the electron in the electron transport
chain (ETC) was also increased significantly (p<0.05)
in FRF (150 mg/kg) pretreated rats, when compared with ISO
induced rats. These results suggest the cardioprotective effect
of FRF of Dioscorea bulbifera Linn. in ISO induced
MI by attenuating the lipid peroxidation by scavenging free
radicals and modulating the energy producing mitochondrial
enzymes.
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Antiapoptotic Effect of Novel Compound from Herba
leonuri- Leonurine (SCM-198): A Mechanism Through Inhibition
of Mitochondria Dysfunction in H9c2 Cells
X.H. Liu, L.L. Pan, Q.H. Gong and Y.Z. Zhu
Apoptosis of cardiomyocytes induced by oxidative stress
play a critical role in cardiac dysfunction associated with
ventricular remodeling and heart failure. We recently reported
that leonurine attenuated hypoxia-induced cardiomyocyte damage.
In this study, we investigated the mechanism of leonurine
(originally from Herba leonuri but we synthesized
it chemically, it as also called SCM-198) in protecting hydrogen
peroxide (H2O2)-induced
rat embryonic heart-derived H9c2 cells from apoptosis. Exposing
H9c2 cells to H2O2
significantly decreased cell viability, and this was attenuated
by pretreatment with leonurine for 4 h in a concentration-dependent
manner. Meanwhile, leonurine was found to reduce in-tracellular
reactive oxygen species (ROS) generation in H2O2-stimulated
cell. Moreover, H9c2 cells stimulated by H2O2
was accompanied with apparent apoptotic characteristics, including
fragmentation of DNA, apoptotic body formation, re-lease of
cytochrome c, translocation of Bax to mitochondria,
loss of mitochondrial membrane potential (Δψm)
and activa-tion of caspase 3. Furthermore, H2O2
also induced rapid and significant phosphorylation of the
c-Jun-N-terminal kinase 1/2 (JNK1/2), which was inhibited
SP600125 (a JNK1/2 inhibitor). All of these events were attenuated
by leonurine pre-treatment. Taken together, these results
demonstrated that leonurine could protect H9c2 cells from
H2O2-induced
apoptosis via modulation of mitochondrial dysfunction
associated with blocking the activation of JNK1/2.
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Restoration of Cardiomyocyte Function in Streptozotocin-Induced
Diabetic Rats after Treatment with Vanadate in a Tea Decoction
T.A. Clark, T.G. Maddaford, P.S. Tappia, C.E. Heyliger,
P.K. Ganguly and G.N. Pierce
Diabetes mellitus is associated with abnormal cardiomyocyte
Ca2+ transients and contractile
performance. We investigated the possibility that an alteration
in inositol trisphosphate/phospholipase C (IP3/PLC)
signalling may be involved in this dysfunction. Phosphatidic
acid stimulates cardiomyocyte contraction through an IP3/PLC
signaling cascade. We also tested a novel therapeutic intervention
to assess its efficacy in reversing any potential defects.
Diabetes was induced in Sprague-Dawley rats by streptozotocin
treatment and maintained for an 8 week experimental period.
Active cell shortening was significantly depressed in cardiomyocytes
obtained from diabetic and insulin-treated diabetic rats in
comparison to normal control animals. Perfusion of the cells
with phosphatidic acid induced an increase in contraction
of control rat cardiomyocytes whereas its effect was inhibitory
in cells from streptozotocin-induced diabetic rats. Diabetic
rats were also treated orally with vanadate administered in
a black tea extract (T/V) for the 8 week period. T/V treatment
resulted in a contractile response that was not different
from cells of control animals. Furthermore, cardiomyocytes
from T/V-treated animals exhibited significantly improved
Ca2+ transients in comparison
to diabetic animals and exhibited a normalized response to
phosphatidic acid perfusion. It is concluded that a T/V glycemic
therapy is capable of preventing the defect in IP3/PLC
signaling that occurs in diabetes and can restore normal cardiac
contractile function.
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Diet and Heart Health: Moderate Wine Drinking Strengthens
the Cardioprotective Effects of Fish Consumption
J. de Leiris, S. Besse and F. Boucher
Growing evidence indicates that the Mediterranean diet
is beneficial to human health. Many epidemiological and research
studies have reported that this diet pattern is able to limit
the development and progression of coronary heart disease,
one of the leading cause of morbidity and mortality in both
developed and developing countries worldwide. There is now
a large consensus about recommending Mediterranean diet to
reduce atherosclerosis and coronary artery disease and to
limit the risk of fatal complications such as sudden cardiac
death and heart failure. This review underlines the role of
two of the specific components of the Mediterranean diet,
namely marine omega-3 fatty acids and wine, and the link between
moderate wine consumption and fatty acid profiles.
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