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Background & General Info
Pomegranate, or botanically speaking Punica granatum, belongs to the family Lythraceae, a group of flowering plants of worldwide distribution but mostly in the tropics.
Regarded as a vital commercial fruit crop and one of the oldest known edible fruit, pomegranate is extensively cultivated in various parts of Asia, North Africa, the Mediterranean, and the Middle East but has now also been admired as an ornamental tree and shrub in parks and gardens of arid and semiarid zones. 
Pomegranate fruits have been exceedingly cherished for their flavor since ages, being either eaten fresh or processed into juice, jams, syrup, and sauce,  and are recognized by majority to be a cheap but healthy “superfood” due to their multifunctionality and nutritional benefits in the human diet.
Pomegranate is a drought-tolerant deciduous shrub or small tree that grows to a height of 6 to 10 meters high and thrives on calcareous, alkaline soil and on deep, acidic loam. The plant is characterized by its numerous spiny branches; glossy, oblong, evergreen leaves; and bright red flowers with three to seven red, white, or variegated petals. It has a long lifespan, with documentation of specimens at Versailles, France, known to have survived for two centuries. It bears nearly rounded reddish fruits that encapsulate several ruby-red juicy seeds that number from 200 to about 1400 and that are coated in water-laden pulp. Inside the fruit are membranous walls that separate the interior into multiple compartments that tightly pack the seeds around a white spongy center. Because pomegranate fruits tend to crack open under rainy conditions, atmospheric humidity, dehydration, or insufficient irrigation to naturally release and disperse their seeds, pomegranate fruits are harvested prior to their full maturity. 
History & Traditional Use
Not only has pomegranate been heralded as one of nature’s “miracle fruit” due to its vast medicinal properties over centuries, but also it has been venerated as a sacred and mythological symbol of various world religions and cultures. For example, in Buddhism, pomegranate is considered one of the three blessed fruits, along with peach and citrus that symbolize longevity and happiness, respectively. Pomegranate on the other hand symbolizes fertility and represents the essence of favorable influences. A Buddhist legend even illustrates how Buddha extinguished the evil habit of the demoness Hariti of abducting the children of others whom she fed to the hundreds of children of her own; in the end, she swore a vow to be a protector of all children and to only eat pomegranates instead of children’s flesh.  Chinese ceramics often depict pomegranate as a symbol of fertility, abundance, posterity, numerous and virtuous offspring, and a blessed future, and other forms of art illustrating a ripe open pomegranate are usual wedding gifts. The Judaists believe that pomegranate seeds total 613, with one seed representing each of the Bible’s 613 commandments, and have featured the fruit in architectural designs. 
Through the ages, preparations of different parts of pomegranate plant, including the flower, fruit juice, rind, and bark, have been used to relieve and remedy numerous conditions. Even during the time of early Roman medical writers, the rind and root bark of pomegranate have been enlisted as potent cure of tapeworm infestation and diarrhea. 
General Herbal Uses
Quite a few studies over the past decades have been published on the antioxidant, anticancer, and anti-inflammatory properties of pomegranate constituents, with most research focusing on treatment and prevention of cancer, cardiovascular disease, diabetes, dental conditions, erectile dysfunction, bacterial infections and antibiotic resistance, and skin damage induced by ultraviolet radiation.  Pomegranates have also found potential applications in the prevention and/or treatment of infant brain ischemia, male infertility, Alzheimer’s disease, arthritis, and obesity. 
In Ayurvedic medicine, pomegranates are a celebrated source of traditional remedies that date back thousands of years. Pomegranate fruit is believed to be potent in pacifying and balancing “pachak pitta” (stomach metabolism), “ranjak pitta” (the heat in the blood), “alochak pitta” (the fire in the eyes), “bhrajak pitta” (the metabolic functions in the skin), and “sadhak pitta,” or the pitta that manages the emotional heart.  Peels from pomegranate are traditionally decocted in India, Tunisia, and Guatemala and are applied as astringents and germicides and for treating aphthae and diarrhea. In the eastern provinces of India, pomegranate rind is used against malaria. 
Approximately half of the total weight of pomegranate fruit is edible, which comprises 80% juice and 20% seeds; the fresh juice consists of 85% moisture, 10% total sugars, 1.5% pectin, and antioxidants, including ascorbic acid and polyphenols.  It is estimated that around 18% of dried and cleaned white pomegranate seeds are oil, which is rich in punicic acid (65%) , a polyunsaturated fatty acid possessing several biological properties, for example, antidiabetic, antiobesity, antiproliferative, and anticarcinogenic activity against different cancer types.  The bark and roots of pomegranate tree, on the other hand, contain copious amounts of alkaloids and, in folk medicine, are used to eliminate worms infesting the human gastrointestinal tract. 
The health benefits of pomegranate juice, especially its high-level antioxidant activity, are greatly linked to its total polyphenol, anthocyanin, and hydrolyzable tannin contents. Ellagic acid derivatives, anthocyanins, and hydrolyzable tannins in pomegranate juices were identified and quantified in the study of Gil et al. (2000).  Although it differs among pomegranate varieties, the content of soluble polyphenols in the juice ranges from 0.2% to1.0% and includes mostly cyanidin-3-glycoside, cyanidin-3,3-diglycoside, and delphindin-3-glycoside (anthocyanins) and catechins, ellagic tannins, and gallic and ellagic acids (anthoxantins). 
The table below illustrates the general compound composition of pomegranate juice extracted from Wardey and Manfalouty pomegranate cultivars through pressing and blending methods, according to the study carried out by Ismail et al. (2014). 
Research-wise, pomegranates and their juices have received substantial attention from the scientific community due to the broad range of disease factors that it can help prevent or treat, including high blood pressure, high cholesterol, oxidative stress, hyperglycemia, and inflammation.  Pomegranates owe these valuable qualities to certain components they possess, in particular polyphenols, which have potential antioxidant, anti-inflammatory, and anticarcinogenic effects according to gathered data.
A steadily growing number of clinical researches have focused on the effect on pomegranate on hypertension and overall cardiovascular health, more possibly out of the timely need to address hypertension as the most common disease found in patients in primary care. Overall, many studies have persuasively pointed out that pomegranate is a “heart-healthy” fruit. 
Aside from forgetfulness and patient ignorance, the concern for adverse effects from standard antihypertensive medications is among the multiple reasons for the hesitancy to commence drug management. Pomegranate is very rich in polyphenols, which have been shown to bear an inverse relationship with cardiovascular diseases.  The juice from pomegranate has been demonstrated to exert anti-atherosclerotic, anti-aging, and antioxidative properties, with the antioxidants such as tannins and anthocyanins having been shown to reduce systolic blood pressure. Additionally, pomegranate juice consumption inhibits serum ACE activity  and prevents the development of atherosclerosis and in turn its associated harmful cardiovascular events by protecting low-density lipoproteins (“the bad cholesterol”) and high-density lipoproteins (“the good cholesterol”) from oxidation.  The polyphenols can protect low-density lipoproteins against cell-mediated oxidation through two pathways—directly, by interacting with the lipoprotein, and indirectly, by their accumulation in arterial macrophages. The study of Aviram et al. (2002) indicated that supplementation of polyphenol-rich pomegranate juice in the diet of atherosclerotic mice significantly inhibited atherosclerotic lesions from developing, and this effect can be linked to the protection of low-density lipoproteins against oxidation. 
A randomized, placebo-controlled, double-blind study in 2005 investigated the effect of daily 3-month consumption of pomegranate juice on myocardial perfusion in 45 patients with coronary heart disease and myocardial ischemia, who have been randomly assigned to either experimental or control group. In this study, both groups manifested the same levels of stress-induced ischemia at baseline (p >0.05), but after 3 months, the experimental group exhibited decreased extent of stress-induced ischemia; this increased however in the control group. In either group, the benefit was observed without changes in cardiac medications, blood sugar, hemoglobin A1c, weight, or blood pressure.  In another study by Aviram et al. (2004) investigating the effects of pomegranate juice consumption on the progression of carotid lesions and changes in oxidative stress and blood pressure in atherosclerotic patients suffering from carotid artery stenosis, the patients supplemented with pomegranate juice demonstrated significant reduction in intima media thickness (by up to 30%) after 1 year, whereas the control group experienced a 9% increase in intima media thickness of the common carotid artery. Moreover, there was an observed decrease in systolic blood pressure (by 12%) after 1 year of pomegranate juice consumption. These favorable effects have again been attributable to the strong antioxidant properties of the polyphenols found in pomegranate. 
Diabetic patients benefit considerably from pomegranate as its antioxidants are not free, but are attached to pomegranate sugars and increase the activity of paraoxonase 1 (PON1), a hydrolytic enzyme associated with high-density lipoprotein that breaks down damaging oxidized lipids in lipoproteins, in macrophages, and in atherosclerotic plaques. 
In the study of Gil et al. (2000) wherein antioxidant activity was evaluated by ABTS, DPPH, DMPD, and FRAP methods, the antioxidant activity of commercial pomegranate juices was three times higher than those of red wine and green tea infusion, with pomegranate juice containing 1500–1900 mg/L of punicalagin. 
Consumption of pomegranate in diet has been noticed to be chemoprotective; that is, it prevents the development or progression of various forms of cancers that affect heavily a large population, causing death. The conclusive findings from the study of Kohno et al. (2004) indicated that pomegranate seed oil could suppress colon carcinogenesis induced by subcutaneous injections of azoxymethane in male F344 rats. Such inhibition of colonic tumors was related to the increased content of conjugated linoleic acid in the colonic mucosa and liver and/or elevated expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) protein in the non-tumor colon mucosa. 
Gasmi and Sanderson (2010) investigated the effects of thirteen pure compounds present in pomegranate on androgen-dependent human prostate cancer cells with regard to their growth-inhibitory, antiandrogenic, and pro-apoptotic activities. In this study, the prostate cancer cells were exposed to 1–100 μM concentrations of pomegranate compounds in the presence of 0.1 nM dihydrotestosterone. At concentrations of 10 μM and above, the cell growth stimulated by DHT and the expression of the prostate-specific antigen and steroid 5α-reductase type 1 were suppressed by four compounds, namely, epigallocatechin gallate, delphinidin chloride, kaempferol, and punicic acid. Above all, punicic acid was observed to induce intrinsic apoptosis via a caspase-dependent pathway. 
Punicic acid from pomegranate seed oil has been demonstrated in the study of Grossmann, Mizuno, Schuster, and Cleary (2010) to inhibit breast cancer. In this investigation, the proliferation of an estrogen-insensitive breast cancer cell line (MDA-MB-231) and an estrogen-sensitive cell line developed from MDA-MB-231 cells (MDA-ERalpha7) was suppressed by 92% and 96%, respectively, compared with cells not treated with 40 μM punicic acid. Punicic acid also stimulated apoptosis in the breast cancer cell lines previously mentioned by 86% and 91%, respectively, and disrupted the mitochondrial membrane potential of these cells. 
A number of recent studies have documented that supplementation with pomegranate fruit extract inhibits inflammatory symptoms in vivo. The results of the study of Shukla et al. (2008) afford an essential insight on the anti-inflammatory activity of bioavailable compounds derived from the polyphenol-rich extract of pomegranate fruit, which inhibits inflammatory cytokine-induced production of prostaglandin E2 (the chief mediator of inflammation in diseases such as rheumatoid arthritis and osteoarthritis) and nitric oxide in vivo. Rabbit plasma samples were collected before and 2 hours after oral supplementation of pomegranate extract and then were tested.
Pomegranate extract or the compounds derived from it qualify for pharmacological development for the treatment of osteoarthritis and other degenerative or inflammatory diseases. Pomegranate extract acts as inhibitors of MKK and p38 mitogen-activated protein kinase (MAPK) signaling pathways in osteoarthritis whose activation leads to the production and expression of different mediators of cartilage catabolism. In the study of Rasheed, Akhtar, and Haqqi (2010), polyphenol-rich pomegranate extract was demonstrated to suppress the interleukin-1β -induced activation of MKK3 and p38α -MAPK isoform and DNA binding activity of the transcription factor RUNX-2. 
The use of pomegranates as an antibacterial agent has a long history that goes back to biblical times; for instance, several kinds of infections were dealt with by the Egyptians using pomegranates. Currently, numerous small studies have investigated the bactericidal effects of pomegranates against various highly pathogenic and drug-resistant strains and determined the bactericidal potency of different pomegranate extracts utilizing disc diffusion assays or minimum inhibitory concentration (MIC). Among petroleum ether, chloroform, methanol, and water extracts of pomegranate tested in vitro for their antibacterial activity in the study of Prashanth, Asha, and Amit (2001), the methanolic extract displayed the broadest antibacterial activity against all tested microorganisms.  Similarly, in the study of Fawole, Makunga, and Opara (2012), methanolic extracts from pomegranate peels demonstrated strong broad-spectrum activity against Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae), with an MIC ranging from 0.2 to 0.78 mg/ml.  In another study, 80% methanolic extract of pomegranate peels significantly inhibited Listeria monocytogenes, S. aureus, E. coli, and Yersinia enterocolitica, with the MIC of the extract against Salmonella enteritidis being the highest (4 mg/ml). 
Through real-time polymerase chain reaction, plaque assay, and TCID 50% hemagglutination assay, Haidari et al. (2009) determined that pomegranate polyphenol extract hampered the replication of influenza A virus in MDCK cells and suppressed the agglutination of chicken red blood cells (cRBC) by influenza virus, indicating that pomegranate polyphenol extract is virucidal. Furthermore, the extract also inhibited viral RNA replication, as determined by the single-cycle growth conditions. 
Pirbalouti, Koohpayeh, and Karimi (2010) reported the wound healing activity of ethanolic extract derived from pomegranate flowers topically administered in rat models. Upon measurement of the wound size, the test groups manifested wound size that reduced early as compared with the control group. Additionally, the extract significantly increased the rate of wound contraction and collagen turnover. 
The very high levels of antioxidant polyphenols existing in pomegranates have been shown to be neuroprotective in different model systems. Hartman et al. (2006) determined that transgenic mice treated with pomegranate juice learned water maze tasks more quickly and swam faster than controls and have roughly 50% less soluble Abeta42 accumulation and amyloid deposition in the hippocampus, signifying Alzheimer’s disease improvement. 
Contraindications, Interactions, And Safety
Consumption of pomegranate as a whole fruit, juice, or extract is generally deemed safe. A 2003 investigative toxicity evaluation of hydroalcoholic pomegranate extract in chick embryo model determined that a pomegranate extract dose of less than 0.1 mg per embryo is not toxic. The extract’s lethal dose (LD50) in OF-1 mice after intraperitoneal administration was 731 mg/kg, with confidence limit of 565–945 mg/kg. Moreover, repeated intranasal administration at a dose of 0.4 and 1.2 mg/kg of extract in Wistar rats led to no toxic effects as regards food intake, weight gain, behavioral or biochemical parameters, and histopathological studies. 
Some studies however warn that over-ingestion of tannin beyond its desired safe level (no more than 0.25%) for long periods can lead to some detriment to health due to the carcinogenic nature of tannin. Excessive intake of the bark and root of pomegranate, which contain a lot of alkaloids such as isopelletierine, may result in emetic and purgative side effects, dilation of pupils, dimness of sight, muscular weakness, and paralysis. 
Since pomegranate intake influences blood pressure, hypotensive people or patients under medications to lower or control their blood pressure should avoid whole fruit pomegranates or pomegranate juice or extract so as not to compound pressure-lowering effects of the drug they are taking.
In Ayurvedic medicine, persons with slow bowel movement or constipation are advised to limit pomegranate consumption since pomegranate improves absorption and hence constipates a person who already has that tendency. 
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Article researched and created by Dan Albir for herbs-info.com. © herbs-info.com 2018
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