The pomegranate (Punica granatum) is a plant known since antiquity for its many therapeutic properties. It helps prevent and treat various disease risk factors including high blood pressure, high cholesterol, oxidative stress, hyperglycemia and inflammatory processes.
Polyphenols are essential components of pomegranate juice and possess a high antioxidant potential, anti-inflammatory and anticancer higher than that of red wine and green tea.
The fruit can be divided into several anatomical compartments such as seeds, peel juice and each of them has very attractive pharmacological activity.
The juice and peel are rich in polyphenols and possess a high antioxidant potential due to the presence of a particular type of tannins called ellagitannins (1). These are widely used in plastic surgery as they prevent the death of the skin flap due to their strong antioxidant activity.
The pomegranate seeds contain phytoestrogens similar to the female sexual hormones and are used to reduce neurodegenerative disorders due to menopause.
The bark and roots are rich in alkaloids, chemicals with potent pharmacological effects even in small doses. It has been used by traditional medicine to treat gastrointestinal worms (2).
Dermatology and Cosmetics
An excessive exposure to the sun can be very harmful for our skin because the penetration of ultraviolet rays form highly oxidizing free radicals which cause serious damage to cellular DNA. This harmful action accelerates the organic and natural aging of the skin with loss of elasticity, formation of dry and rough skin and collagen damage that will give rise to the formation of wrinkles.
The solar light, and in particular its ultraviolet component are the main cause of many harmful effects such as erythema (skin redness), edema, immunosuppression, premature skin aging and the formation of most of skin cancers.
It ‘s a fibrillar protein that makes up 75% of our skin and “paste” the cells that make up between them, also plays an irreplaceable nourishment of action. It provides important elastic properties and its aging leads to the formation of wrinkles.
The body constantly produces its own collagen which is maintained in equilibrium between the synthesis by cells called fibroblasts and the degradation by certain molecules.
The pomegranate has been shown to possess remarkable skin photoprotection properties . In a study published in “Experimental Dermatology” in 2009, he was investigated the efficacy of pomegranate in the prevention of the destruction of collagen mediated by ultraviolet rays.
The antioxidant efficacy of pomegranate has been tested on human “reconstituted” skin (EpiDerm FT-200) that presents morphological, metabolic and growth similar to those of human skin in vivo.
They were used derivatives of the plant such as juice, extract and oil seeds.
The fabric was treated with pomegranate extracts one hour before irradiation and in 12 hours values of the oxidation of proteins were measured, so was the damage of the DNA markers and photo-aging.
It was found that the pre-treatment with pomegranate extract inhibited oxidative stress on DNA mediated by UVB and protected the collagen from degradation of elastic fibers by ultraviolet rays (3).
A clinical study published in the “Journal of Nutritional Science and Vitaminology” 2006, was conducted to evaluate clinically protective effects of ellagic acid (contained in pomegranate) on the pigmentation of the skin after irradiation with ultraviolet rays. They were enrolled 39 women aged between 20 and 40 years.
Each group received the respective test food for 4 weeks in such a manner that a first group of 13 women has taken with food high doses of ellagic acid (200 mg / day), a second low-dose group (100 mg / day) and finally a third group took placebo.
Each subject received a minimum dose of irradiation (minimum erythema dose) on the inner region of the right arm and the erythema intensity was measured both before and after the 4 weeks of intake of the food.
The intensity values of the erythema post-exposure were significantly decreased (compared to the control group) in the group that had taken high doses of ellagic acid (- 1.73%) both in the one treated with low doses (-1, 35%).
In conclusion on the basis of the results obtained the assumption of ellagic acid with the pomegranate extract it has been shown to have an inhibitory effect on a slight pigmentation of human skin caused by irradiation with ultraviolet rays. Whereas this same type of damage is the major cause of wrinkles, it is understandable that this fruit has a remarkable anti-aging action (4).
At the cardiovascular system level, the pomegranate has an important antihypertensive activity, anti-inflammatory and antiaterogenica.
Atherosclerosis is a chronic inflammatory disease of the arteries of large and medium caliber. The term refers all’inspessimento and accumulation of lipids on the inner surface of blood vessels (called intimate). This process in the years gives rise to the so-called “atherosclerotic plaque” that will only grow if the amount of lipids from the blood entering the arterial wall exceeds the amount removed from particular cells “scavenger” called macrophages.
Over time, the plaque will undergo profound transformations which in many cases will give rise to dangerous complications such as ulcerations and erosion with thrombus formation and consequent partial or complete occlusion of the vessel. As a result, you will have either a part of organ circulation deficiency (ischemia) or a total deficit resulting in heart attack.The cells lining the inner surface of vessels are called “endothelial cells” calls and are characterized by many important functions. They possess a high metabolism that determines the synthesis of important factors to endothelial vasodilator a and antithrombotic action which is fundamental to keep the lumen patent and always suitable to the passage of blood.
Under normal conditions it prevails vasodilatory and antithrombotic effects that have an adequate blood flow, but when they take damage operated by various risk factors such as increasing the bad cholesterol (LDL), high blood pressure, smoking and diabetes, these cause profound alterations in endothelial function that losing its antithrombotic capacity will produce inflammatory chemical mediators that favor the growth of the thrombus rather than fight it.As mentioned above the increase in the so-called “bad” cholesterol, represented by the LDL lipoproteins, is the indispensable condition and fundamental for the onset and the progression of atherosclerosis, and more specifically the oxidation of such particles is the element that it promotes the development of atherosclerotic lesions.
The oxidation of cholesterol microspheres (LDL) leads to their transformation to the point that they are no longer recognized by the immune system of the body which creates an immune reaction against them giving origin to an inflammatory process involving the inner surface of the typical vessels of atherosclerotic disease.From this it follows the great importance to assume a healthy lifestyle based on abstention from smoking (strong oxidant), consumption of adequate amounts of fruits and vegetables (powerful antioxidants), weight control (obesity promotes oxidative processes ), reducing sugars (powerful oxidizing) and an adequate and constant movement that promotes an increase in antioxidants.
The Pomegranate in this clinical context performs many beneficial actions going to counteract the oxidative processes and reducing the trend towards the formation of atherosclerotic plaque.
The plant flavonoids contained in pomegranate act as powerful inhibitors of the oxidation of low density lipoproteins (LDL) (5-6)
and also inhibit the oxidation of macrophages, the cells responsible for the disposal of fat (7). A diet of flavonoids has shown to be inversely proportional to coronary heart disease mortality (8).
It ‘ s been shown an inverse association between the intake of flavonoids in the diet and the subsequent onset of ischemic heart disease and cerebrovascular disease (9-10).
Atherosclerosis and Compromise Heart
In a study published in “Clinical Nutrition” 2004 pomegranate juice was administered to 10 patients with a carotid stenosis (narrowing of the neck vessels that carry blood to the brain) and have been studied both the progression of carotid lesions both changes oxidative stress and blood pressure.
In the control group who had not consumed pomegranate juice, after a year of study the thickness of the carotid artery was increased by 9%, while in the group treated with the juice, integration involved a reduction in the thickness of up to 35%.
The total antioxidant status was increased by 130% after a year of pomegranate juice consumption.
Systolic blood pressure was reduced, again after a year of treatment of 12%. For all the studied parameters, the maximum effects have occurred after a year and the continuation of the assumption up to three years did not lead to further improvements (11).
In an another clinical trial published in the “American Journal of Cardiology” 2005 they were studied 45 patients with cardiovascular disease with a mean age of 69 years. Many had already suffered heart attacks, most had hypertension and hypercholesterolemia.
Divided into two groups, the first drank 240 ml for three months of pomegranate juice and the other took a placebo.
At the end of the trial all were subjected to a “myocardial perfusion test,” a test that measures the blood supply to the heart during exercise.
The group that drank pomegranate juice recorded a 17% increase in the blood supply, while in the placebo group recorded a decrease of 18%.
Moreover, the researchers revealed that episodes of angina (severe chest pain) were decreased by 50% in the group treated with pomegranate and rose 38% in the placebo group (12).
These data are very significant because the myocardial perfusion test is a reliable predictor element as regards the possibility that a patient, suffering from vascular disease, can meet or less to a heart attack.
In conclusion the daily intake of juice can improve “blood” flow in the heart of patients have long affected by coronary artery disease, demonstrating that the flavonoids contained in it act not only in prevention (on healthy subjects) but also as a therapy in sick subjects.
The inner surface of the arteries is covered by really important cells called « endothelial » which among their functions also include that of producing a very important gas : nitrogen oxide.
This substance is so important that it is related to 1998 Nobel prize for medicine awarded to American researcher Louis Ignarro “for his discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system” (13).
– At the endothelium level , it plays primary and irreplaceable action as it inhibits platelet aggregation by preventing the formation of thrombus.
– It Releases the smooth muscles of the arteries thus creating a vasodilation that helps to keep blood pressure low.
– It also inhibits the vascular inflammatory process by blocking the adhesion of white blood cells to the inner surface of the vessels.
These functions are considered unanimously of the utmost importance for the prevention of atherosclerosis (14).
In a study published in “Nitric Oxide” in 2006, pomegranate juice has been tested for its ability to protect nitric oxide by the oxidative destruction and improve biological activity. For the experimental test it is more effective than cranberry juice, red wine, vitamin C and vitamin E (all powerful antioxidant agents) in preserving the nitrogen oxide from destruction due to oxidative processes (15).
In another work of Italian school, published in “Proceedings of the National American Science » (2005), the evidence of the experimental data suggests that the polyphenols in pomegranate juice contribute to the reduction of oxidative stress and counteract the formation of the validly atheromatous plaque by raising the concentration of an enzyme (nitric oxide synthetase) , produced in endothelial cells which increases the production of nitric oxide (16).
On “Atherosclerosis” in 2001, a group of researchers studied the antioxidant effect of pomegranate on lowering blood pressure in hypertensive subjects. They were administered 50 ml of the juice daily for two weeks and then evaluated the pressure values and the enzyme activity of angiotensin in converting enzyme (ACE).
At the end of the study we witnessed a 5% drop in systolic blood pressure (maximum value) and a decrease of 31% of angiotensin converting.
The researchers concluded that pomegranate could offer a wide protection against cardiovascular diseases related to its inhibitory effect on oxidative stress and serum ACE activity (17).
The term “diabetes mellitus” refers to a group of metabolic diseases characterized by an increase in the level of glucose in the blood (hyperglycemia). Over time, high blood sugar is liable for damages in the long term at the expense of various organs and systems such as eye, kidney, nerves, heart and blood vessels but ultimately the primitive damage from which spring all the other is represented by damage to blood vessels in the form of atheromatous plaque.Almost all the so-called diabetic complications are resulting from circulation problems: blindness by the impairment of the retinal vessels, kidney failure from kidney damage to blood vessels, neuropathies by poor blood supply to the nerves in the limbs, amputations ( more frequent amputations not related to trauma) due to a reduced and inadequate circulation to the lower limbs.
Very often the increase in blood sugar is also matched by an increase in cholesterol (the dangerous LDL fraction, the protective HDL fraction), an increase in weight and abdominal fat (dangerous), and it becomes essential the metabolic control over the concentrations of these parameters.
The pomegranate has demonstrated an excellent ability in controlling diabetes, in reducing total cholesterol, in increasing the fraction of high density lipoprotein HDL (good cholesterol) that reduce atheromatous plaque responsible for the obstruction of the arteries, and in reducing oxidative processes in the arterial level.
In a study of the “Journal of Agricultural and Food Chemistry” in 2008, a group of researchers recruited and administered to 30 patients with type 2 diabetes either juice (50 ml / day) and extract of pomegranate polyphenols (5 ml /of) during a month. After a month, the increase of enzymes that protect against oxidation HDL (good cholesterol) was 40%. These beneficial effects may delay the development of atherosclerosis in diabetic patients (18).
In Iran in 2006 a study was undertaken, which then appeared in the “International Journal of Vitamin and Nutrition”, to evaluate the effect of concentrated pomegranate on the lipid profile of 22 patients with type 2 diabetes and cholesterol levels above 200 mg / dl . After a month of intaking, it was witnessed a significant decrease in both total cholesterol and LDL (bad cholesterol).
Again, proper intake of pomegranate juice could significantly change the risk factors of cardiovascular disease in diabetic patients (19).
Another very interesting and recent study published in “Atherosclerosis” in 2014, compared the use of simvastatin + placebo versus simvastatin + pomegranate juice.
Simvastatin is a statin:
Statins are drugs used worldwide. It Inhibits a particular enzyme involved in cholesterol synthesis and the mechanism will lower blood concentration.
This rebalancing leads to a substantial reduction of cardiac events and death from coronary heart disease.
After two months of therapy, the levels of free radicals capable of forming atherosclerotic plaques, were decreased by 18% in the simvastatin + placebo group but were rather decreased by 30% in the simvastatin + pomegranate extract group.
In addition the association simvastatin + pomegranate had reduced by 48% the level of triglycerides but not the simvastatin + placebo therapy.
In conclusion, the addition of pomegranate extract to a potent drug such as simvastatin, dramatically improved the level of lipids and oxidative stress, demonstrating that its effectiveness was independent of other therapeutic variables (20).
Reduction of oxidative stress
To evaluate this parameter, a group of researchers administered to 10 diabetic patients of pomegranate juice (50 ml / day) for three months, by measuring the oxidation levels in the blood.
The conclusions were that the concentration of oxidized lipids (and therefore suitable to form the atheromatous plaque) was decreased by 58% and the overall level of cellular oxidation was decreased by 71%!
Not only that , but the concentration of glutathione was increased by 141%.
The researchers concluded that supplementation with pomegranate juice in diabetic determined powerful antioxidant effects that could contribute to the mitigation of the development of atherosclerosis in these patients (21).
It was shown that the pomegranate fruit may be used in prostate cancer treatment since it is able to inhibit cell growth and induce apoptosis (cell suicide) of cancer cells. It ‘s been experimentally demonstrated that pomegranate juice inhibits the activity of Nuclear Factor (NF-kB).
This is an important mediator whose intracellular increase promotes the proliferation of tumor cells, also increases the number of those which are in active replication and favors the formation of metastases (22).
The first clinical trial on the administration of pomegranate juice in patients with prostate cancer was conducted by Pantuck and co. in 2006.
The study included men with rising PSA (prostate specific antigen) that persisted after treatment with surgery or radiation.
This laboratory parameter is very useful for checking in time cases already treated and its increase is a recurrence of the disease index.
In patients who had taken 240 ml of pomegranate juice containing 550 mg of total polyphenols, it was monitored the doubling time of PSA that indicates the rate at which the tumor progresses and is an excellent predictor of survival.
Before treatment the doubling time, ie the time necessary to the PSA to increase eg: from 2 to 4, was 15 months; after the treatment was 54 months !! From these data we can deduce the huge slowdown in the growth of the tumor.
Not only that, but experiments were performed in vitro on cells of the serum of patients and proved to be a 12% decrease in cell proliferation and an increase of 17% apoptosis of cancer cells which indicated an increase of their mortality.
The study was conducted for two years on 40 patients with prostate cancer and progressive increase in PSA, beyond the ‘85% of the participants responded positively to the pomegranate juice (23-24).
The statistically significant prolongation of the doubling time of PSA accompanied by laboratory experiments on cell proliferation leads to the logical conclusion that pomegranate juice is worth running double-blind, randomized and compared with placebo.
On this sensitive and difficult issue oncology comes the obligation to remember the proven beneficial effects of another spice used daily: green tea with its active ingredient epigallocatechin gallate (EGCG). The study of Bettuzzi of 2006 (25) showed that the prostate cancer recurrence after a year of treatment with 600 mg of EGCG were decreased by 90% in 30 men suffering from this tumor.
Today on the market, as a product pharmaceutics, it is available in the form of pomegranate ellagic acid punicosides to 40% and you can set up the galenicals with very precise dosages.
One interesting treatment schedule is what we propose below
THERAPY IN PHOTOS PREVENTION
In the morning after breakfast:
1 cps 400 mg of EGCG + 1 cps 400 mg of ac. Ellagic (pomegranate)
At night after dinner:
1 cps 400 mg of EGCG after dinner + 1 cps 400mg of ac. Ellagic
These doses in special clinical conditions can be significantly increased on expert medical prescription.
Recovery muscle strength after exercise
Many athletes using pomegranate juice after intense weight lifting exercise found a more rapid recovery of the forces.
In a study published in “Medicine and Science in Sports & Exercize” in 2010, the goal was to determine whether supplementation with pomegranate extract after exercise was able to accelerate the recovery of muscle strength.
Two groups of athletes were treated one with pomegranate juice and the other with placebo.
With both treatments (placebo or juice) strength was also reduced after two hours exercise (ie by 72% from baseline), plus the recovery of strength was incomplete in both groups after 96 hours. However, after 48 hours from the exercise strength it was significantly higher (80%) in athletes treated with pomegranate than those who received placebo (26).
The pomegranate, like any plant or spice, while performing an action on multiple metabolic pathways (multi-target action) retains some preferential targets which operates a more intense and determined.
The cardiovascular system is definitely a large target where many metabolic pathways are modulated by the fruit extracts. The inhibition of cholesterol oxidation, the effect anti-inflammatory and anti-vascular activity hepatic steatosis (fatty liver infarction) are a prime example.
Pomegranate has also demonstrated good anti-tumor preventive action particularly in the prostate, where it would be very interesting to test plant extracts combined with green tea, strong well-designed clinical studies as proposed above.
There is evidence in animal studies, unfortunately, indicate that the therapeutic possibilities in arthritis where it seems that the pomegranate is capable of inhibiting potent inflammatory factors (27).
The same applies to rheumatoid arthritis, severe autoimmune disease that leads to permanent disability if not treated, where the pomegranate extract reduces the incidence and the onset of experimentally induced arthritis in mice treated with collagen (28).
Pomegranate, with in vitro studies, have been recognized for outstanding antimicrobial properties (2-29). The powder extracted from the peel of dried fruit possesses a high degree of inhibition on Candida albicans, an important fungus pathogenic to humans in particular conditions of immunosuppression (30).
Furthermore, a peel of pomegranate extract in combination with copper ions (Cu) improves the antimicrobial effects against the formidable Staphylococcus aureus methicillin-resistant (antibiotic-resistant) (31).
In a study published in “Quintessence International” in 2011, it was reported, the net effect on dental plaque level of a mouthwash containing pomegranate. It was also compared against the chlorhexidine (chemical synthesis disinfectant very common and used). The results have shown similar efficacy for both (32).
In addition, the hydroalcoholic extract of pomegranate is very effective against microorganisms of dental plaque with a decrease of 84% of the bacterial colonies (33).
An ointment made from pomegranate to 5% was evaluated in wound healing induced in guinea pigs. The ointment has greatly improved the contraction of wounds and re-epithelialization period. It showed significant antioxidant and antimicrobial properties against bacteria and fungi “difficult” as Streptococcus pneumoniae, Pseudomonas aeruginosa and Aspergillus niger. It was safe, effective and free of toxic effects (34).
Finally in male rats pomegranate juice has been shown to increase concentration and sperm motility, the diameter of the seminiferous tubules and thickness of the layer of germ cells (35).
From these experimental data you can guess how far there is still to go to fully understand the vast properties of this fruit which is at present a great “natural pharmacy” not fully explored yet.
Dott. Claudio Sandri
Translated by Ms Jeanne Marie Arcaini
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