Grape Seed Extract and its Effects on Diabetes and its Complications
Authored by Hannah R Vasanthi
Abstract
The steady exponential increase of the number of
diabetics world over, demands the challenge of undertaking novel
therapeutic measures to counteract the fatal disease: Diabetes mellitus.
Based on the current global statistics, it is safe to assume that the
human population is in the midst of a Diabetes epidemic. Despite novel
therapeutic and pharmacological approach to counteract this epidemic,
diabetes still poses a threat as its complications leads to major
associated disorders mounting to huge economic burdens as well.
Phytochemicals and natural therapeutic approaches have been increasingly
proven to provide a head on approach to deal with disease and its
related disorders. The phytoconstituents of grapes have proven to be a
treasure chest of relevant potential pharmacological lead molecules to
manage and cure metabolic disorders. This review deals with various
comprehensive approaches of bioactive molecules present in grape seed
extract and their effective nature in treating chronic hyperglycemia.
Abbreviations: GSE: Grape Seed Extract; STZ: Streptozotocin; ROS: Reactive Oxygen Species
Introduction
It is estimated by 2030 there will be 205 million
more people with diabetes in addition to the 387 million currently on
board. According to this estimate at present, for every twelve
individuals in the world one among them is affected by diabetes [1-3].
India however has an alarming statistical report of 62.1 million
diabetics with a 100 million of total population and by 2030 this number
of diabetics is predicted to escalate to nearly 79.4 million [4,5].
Diabetes is commonly referred as a 'metabolic disorder', 'a life-style
disease', now diabetes can also be referred 'the most expensive disease'
as well, partly because it is considered an epidemic and currently
around US $376 million is been sent on diabetic care and research, which
will be projected to exceed US $490 million by 2030 [6]. Parallel to
this expenditure, India spends around 180,000 million Rupees on the same
cause annually [7]. Despite the amount of resources spend to curb this
insidious disease in our hand, the cure or the solutions always seem to
be elusive.
To sustain the plethora of molecular and biochemical
activities, the cells are in a constant need for energy or glucose. Most
of the glucose supplemented to plasma is through dietary sources or
non-dietary sources through glycogenolysis, formation of glucose via
other carbon compounds in the system like pyruvate, lactate, amino acids
etc [8]. The anatagonistic role of glucagon and insulin hormones plays a
vital role in the homeostasis of plasma glucose level. However faulty
insulin secretion and or insulin resistance along with genetic and
environmental factors most often result in hyperglycemic condition of
the cell. At this stage, diabetes is the summation of chronic
hyperglycemic condition in the cell [9,10].].
Prolonged diabetic condition in the system also leads
to further deleterious effect known as diabetes related complications
which could be classified as macro vascular complications which include
obesity, coronary heart disease etc and micro vascular complications
which includes diabetic nephropathy, retinopathy and neuropathy. Less to
none physical activity, stressed lifestyle, overconsumption of high
calorie diet along with genetic and medical factors for a prolonged time
without proper treatment or adequate lifestyle modifications may very
often lead to morbidity and mortality [11,12]. But the actual treatment
of diabetes is aimed at maintaining normal, clinically significant
glucose values, to create a comparable normal quality of and to prevent
the progression of diabetes related vascular complications with the
intervention of drugs. Chronic hyperglycemia may be a major reason for
diabetic complications but it is not the only reason, oxidative stress
resulted through glucose toxicity in cell acts as a major contributor
for diabetic complications [13]. Hyperglycemic conditions in the cell
persuades the ROS production through various mechanisms like advanced
glycation end products, sorbitol accumulation, cytokines activation etc.
Hence a more sensible way to curb diabetes is to not only treat the
presenting condition but to act on various molecular and biochemical
levels [14]. This review analyses the various compounds present in the
grape seed extract, bioactivity and its efficacy against the biochemical
and molecular conditions of diabetes and its related complications.
The seed for diabetes - Grapes and Grape seed extract
Among many theories and paradoxes about Diabetes
mellitus and its complications, the most interesting one is 'the French
paradox'. According to this paradox, the French people consume far more
mono saturated fatty acids than the Americans; however when it comes to
metabolic disorders like diabetes, obesity or cardiovascular diseases,
the Americans are more prone than the French. The possible explanation
in conjecture to this observation is that the French people consume more
wine than the Americans. Many scientific studies have said the
polyphenols and flavanoids present in red wine might be the contributing
factor for this conundrum [15].
The wine contains certain phenolic compounds like
proanthocyanidins, epicatechin, dimeric procanidin, gallic acid which
are also present in the grape seed extract [16]. The development of
health supplement from phytochemicals proves to be an exciting research
opportunity for many diseases especially pertaining to the metabolic
disorders. Grape seed extract (GSE) is one such excellent health
supplement from natural sources (mainly from the grape species European
grapes-Vitis vinifera, North American grapes - Vitis labrusca and Vitis
rotundifolia, and Hybrids of certain French varieties [17].
Grape seed extract is the by-product of wine and
juice processing industry. A majority of oligomeric proanthocyanidins
are present in commercialized, standard grape seed extract with an
inculsion of around 5%-8% of monomeric flavanols. GSE has a rich source
of catechin, epicatechin, epicatechin-3-O-Gallate along with the most
potent and readily available proanthocyanidins also with these monomeric
phenolic compounds, grape seed extract has a rich source of dimeric,
trimeric and tetrameric procyanidin. The red color and astringency taste
of the GSE can be attributed to polyphenol rich compounds especially
proanthocyanidins which may affect the color and sensory characteristics
of the extract [16,18,19].
Grape Seed Extract takes on Diabetes
Diabetes is an unhealthy culmination of different
factors which affect and alters metabolism at various levels. The basic
therapeutic approach towards the treatment of diabetes is by reducing
the postparandial hyperglycemia by attenuating the absorption of
glucose. In a normal, metabolic condition, this is achieved by the
enzymes alpha-glucosidase, alpha-amylase and pancreatic lipase [20,21].
The ethyl acetate fraction of Muscadine grapes (Vitis roundifolia) has
anti-glucosidase and pancreatic lipase activity which could be
attributed to the phenolics such as quercetin and ellagic acid, present
in the seeds [21] also the aqueous extract of grape seeds are potent
alpha glucosidase and alpha amylase inhibitors [22]. The oligomers of
grape seed procyanidin extract phosphorylates the insulin receptor and
thus activates to increased cellular glucose uptake in 3T3L1 cells [23].
Further it was confirmed that procyanidins from the grapes increased
the cellular glucose uptake in insulin sensitive L6E9 and 3T3L1 cell
lines by insulin-mimetic property [24].
The antioxidant activity of any compound refers to
the delay or inhibition of step of the oxidative chain reactions or
forming stable radicals [25] the effect of platelet release from
reactive oxygen species incubated with the extracts from grape skins or
seeds were examined and the results led to an immediate attenuation of
release of the inflammatory mediator, soluble CD40 ligand which leads to
the conclusion of the extract's anti-oxidant property [26]. In the
diabetic rat model, oral administration of GSE reduced the levels of
lipid peroxides and carbonylated proteins and improved the antioxidant
activity, suggesting that the grape seed extract enhanced the
antioxidant defense against reactive oxygen species produced under
hyperglycaemic conditions [27].
It is not surprising that the benefits of GSE, are
extended in the in vivo studies as well, this may be attributed to the
fact that grape seed extract have less toxicity for regular consumption
[28]. In a study of high-fructose diet induced insulin resistance and
oxidative stress in rats, grape seed extract administered rats showed
significant improvement in oral glucose tolerance and reduction of
plasma glucose levels with insulin concentrations [29]. GSE also
exhibits pronounced hypoglycemic properties in STZ induced diabetic rats
[24]. When the red grape pomace extract was administered to STZ induced
C57BLKS/6NCr mice, results show that there was a 35% decrease in
post-parandial hyperglycemia [30].
A plausible reason behind the diabetes related
vascular complications is, Advanced Glycation End products (AGE) or
Protein Glycation products (PG). The Amadori product formed due to the
reaction of free amino groups with carbonyl group of reducing sugar,
forms a reactive carbonyl species such as 3-deoxyglucosone. These
processes have implications in the structural and functional
extracellular proteins in the vascular region, leading to vascular
complications [31]. Under experimental conditions, Muscadine grape skin
and seed extract have proven to inhibit the PG [32] which leaves us to
believe that in addition to having anti-diabetic properties, GSE can
also be used for diabetes related complications as well.
GSE when administered to STZ induced diabetic rats,
modulated pathological changes in apoptosis in neurons and glial studies
reveals that it could prevent non enzyme glycation in nerves by
extension the prevention of neuropathy. Also, GSE can ameliorate
allodynia (diabetic neuropathic pain) [33]. The same groups have worked
on the diabetic nephropathy, and have proved that GSE administration
results in anti-non enzyme glycosylation in the nephrons of diabetic
rats [34]. The oxidative stress induced by diabetes on the nephrons of
rat kidney was effectively reduced by GSE, proving it to work for yet
another complication of diabetes [35]. Studies have not been carried out
in diabetic retinopathy however; GSE is proven to prevent cataract
formation in hereditary catractous rats (ICR/f) [35,36]. In an
interesting human study conducted in Netherlands, GSE could be effective
in reducing 24 h energy intake in normal to overweight dietary
unrestrained subjects, and could, therefore, play a significant role in
body-weight management [37].
Conclusion
Our current civilization is subservient to what we
think the modernization of our lifestyle. We are under the constant
battle of good vs feel good; most of our diet comes under processed,
highly refined and high calorie foods. The impacts of these foods or
such lifestyle have an astronomical effect in our system. As much as
unhealthy diet prevails in the consumer market, recently health
supplements seems to have piqued interest among health care
professionals, biomedical researchers, scientists, manufacturers amongst
other people. Specific usage, dosage of herbal supplement, its
mechanism of action, its involvement and interaction with other drug for
the purpose of formulation are some of the many interests that surround
health supplements. Grape seed extract has now proven to be the jackpot
health supplements as it provides overall health benefits to the
consumer. Grape seed both in natural (wine, grape juice) form and as in
grape seed extract provides a holistic approach to a disease. As
described above, grape seed extract not just helps in a particular
symptom of diabetes but rather it provides a complete health care to all
the symptoms and the related complications. Grape seed extract exhibits
anti-diabetic properties as evidenced by biochemical, molecular
studies. Although there are enormous remedial measures to combat the
diabetic plague it is imperative to turn our focus to natural drugs with
complete of its full potential to reap maximum benefits.
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