Research Pomegranates
Effects of pomegranate supplementation on exercise performance and post-exercise recovery in healthy adults: a systematic review
.Ammar A1, Bailey SJ2, Chtourou H3, Trabelsi K3, Turki M1, Hökelmann A4, Souissi N5
Abstract
The functional significance of pomegranate (POM) supplementation on physiological responses during and following exercise is currently unclear. This systematic review aimed (i) to evaluate the existing literature assessing the effects of POM supplementation on exercise performance and recovery; exercise-induced muscle damage, oxidative stress, inflammation; and cardiovascular function in healthy adults and (ii) to outline the experimental conditions in which POM supplementation is more or less likely to benefit exercise performance and/or recovery. Multiple electronic databases were used to search for studies examining the effects of POM intake on physiological responses during and/or following exercise in healthy adult. Articles were included in the review if they investigated the effects of an acute or chronic POM supplementation on exercise performance, recovery and/or physiological responses during or following exercise. The existing evidence suggests that POM supplementation has the potential to confer antioxidant and anti-inflammatory effects during and following exercise, to improve cardiovascular responses during exercise, and to enhance endurance and strength performance and post-exercise recovery. However, the beneficial effects of POM supplementation appeared to be less likely when (i) unilateral eccentric exercise was employed, (ii) the POM administered was not rich in polyphenols (<1·69 g/l) and (iii) insufficient time was provided between POM-ingestion and the assessment of physiological responses/performance (≤1 h). The review indicates that POM has the potential to enhance exercise performance and to expedite recovery from intensive exercise. The findings and recommendations from this review may help to optimise POM-supplementation practice in athletes and coaches to potentially improve exercise-performance and post-exercise recovery.
Source : British Journal of Nutrition
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Pomegranate (Punica granatum L.) peel hydro alcoholic extract ameliorates cardiovascular risk factors in obese women with dyslipidemia: A double blind, randomized, placebo controlled pilot study
- Mahdiyeh Khadem Haghighiana, ,
- Maryam Rafrafa, , ,
- Abdolvahab Moghaddamb, ,
- Salar Hemmatic, ,
- Mohammad Asghari Jafarabadid, ,
- Bahram Pourghassem Gargarie,
Abstract
IntroductionDyslipidemia is one of the most important risk factors for cardiovascular disease. Previous studies have shown that pomegranate and its polyphenols may have hypolipidemic effects. The objective of this study was to evaluate the effects of pomegranate peel extract on some cardiovascular risk factors in patients with dyslipidemia.
MethodsThirty eight obese women (30< body mass index (BMI) >35 kg/m2) with dyslipidemia were allocated into two groups receiving two 500 mg pomegranate peel extract (n = 19) or placebo (n = 19) daily for 8 weeks. Serum lipid profile (total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), triglycerides (TG)), Blood Pressure(BP), serum high sensitive-C reactive protein (hs-CRP) and BMIwere measured.
ResultsPomegranate peel extract significantly decreased post treatment levels of serum TC (p = 0.014), LDL-C (p = 0.021), and TG (p = 0.036) and increased HDL-C (p = 0.020)compared to baseline. There was a significant decrease in Systolic Blood Pressure (SBP) levels and hs-CRP in pomegranate peel group whereas Diastolic Blood Pressure (DBP) levels and BMI remained unchanged after intervention. No significant changes were seen in terms of all post treatment values for the placebo group at the end of trial (p > 0.05). After adjusting for the baseline values, energy intake and weight changes, there were significant differences in post-treatment values between the two groups except in serum concentrations of HDL-C, DBP and BMI.
ConclusionsCurrent study showed a positive effect of pomegranate peel extract in improving cardiovascular risk factors in obese women with dyslipidemia.
Source : Sci-Hub via European Journal of Herbal Medicine
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Chemical analysis of Punica granatum fruit peel and its in vitro and in vivo biological properties
- Kaliyan Barathikannan,
- Babu Venkatadri,
- Ameer Khusro,
- Naif Abdullah Al-Dhabi,
- Paul Agastian,
- Mariadhas Valan Arasu,
- Han Sung Choi and
- Young Ock Kim
Abstract
BackgroundThe medical application of pomegranate fruits and its peel is attracted human beings. The aim of the present study was to evaluate the in vitro α-Glucosidase inhibition, antimicrobial, antioxidant property and in vivo anti-hyperglycemic activity of Punica granatum (pomegranate) fruit peel extract using Caenorhabditis elegans.
Methods Various invitro antioxidant activity of fruit peel extracts was determined by standard protocol. Antibacterial and antifungal activities were determined using disc diffusion and microdilution method respectively. Anti-hyperglycemic activity of fruit peel was observed using fluorescence microscope for in vivo study.
Results The ethyl acetate extract of P. granatum fruit peel (PGPEa) showed α-Glucosidase inhibition upto 50 % at the concentration of IC50 285.21 ± 1.9 μg/ml compared to hexane and methanol extracts. The total phenolic content was highest (218.152 ± 1.73 mg of catechol equivalents/g) in ethyl acetate extract. PGPEa showed more scavenging activity on 2,2-diphenyl-picrylhydrazyl (DPPH) with IC50 value 302.43 ± 1.9 μg/ml and total antioxidant activity with IC50 294.35 ± 1.68 μg/ml. PGPEa also showed a significant effecton lipid peroxidation IC50 208.62 ± 1.68 μg/ml, as well as high reducing power. Among the solvents extracts tested, ethyl acetate extract of fruit peel showed broad spectrum of antimicrobial activity. Ethyl acetate extract supplementedC.elegans worms showed inhibition of lipid accumulation similar to acarbose indicating good hypoglycemic activity. The normal worms compared to test (ethyl acetate extract supplemented) showed the highest hypoglycaemic activity by increasing the lifespan of the worms. GC-MS analysis of PGPEa showed maximum amount of 5-hydroxymethylfurfural and 4-fluorobenzyl alcohol (48.59 %).
Conclusion In the present investigation we observed various biological properties of pomegranate fruit peel. The results clearly indicated that pomegranate peel extract could be used in preventing the incidence of long term complication of diabetics.
Source : BMC Complementary and Alternative Medicine
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Clarification of the molecular pathway of Taiwan local pomegranate fruit juice underlying the inhibition of urinary bladder urothelial carcinoma cell by proteomics strategy
- Ting-Feng Wu
- Li-Ting Hsu,
- Bo-Xian Tsang,
- Li-Chien Huang,
- Wan-Yin Shih and
- Li-Yi Chen
Abstract
Background
Pomegranate fruit has been shown to exhibit the inhibitory activity against prostate cancer and lung cancer in vitro and in vivo, which might be a resource for chemoprevention and chemotherapy of cancer. Our previous documented findings indicated that treatment of urinary bladder urothelial carcinoma cell with the ethanol extract isolated from the juice of pomegranate fruit grown in Taiwan could inhibit tumor cell. In this study we intended to uncover the molecular pathway underlying anti-cancer efficacy of Taiwan pomegranate fruit juice against urinary bladder urothelial carcinoma.
Methods
We exploited two-dimensional gel electrophoresis coupled with tandem mass spectrometry to find the de-regulated proteins. Western immunoblotting was used to confirm the results collected from proteomics study.
Results
Comparative proteomics indicated that 20 proteins were differentially expressed in ethanol extract-treated T24 cells with 19 up-regulated and 1 down-regulated proteins. These de-regulated proteins were involved in apoptosis, cytoskeleton regulation, cell proliferation, proteasome activity and aerobic glycolysis. Further studies on signaling pathway demonstrated that ethanol extract treatment might inhibit urinary bladder urothelial carcinoma cell proliferation through restriction of PTEN/AKT/mTORC1 pathway via profilin 1 up-regulation. It also might evoke cell apoptosis through Diablo over-expression.
Conclusions
The results of this study provide a global picture to further investigate the anticancer molecular mechanism of pomegranate fruit.
Source BMC Complementary and Alternative Medicine
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Protective effects of extracts from Pomegranate peels and seeds on liver fibrosis induced by carbon tetrachloride in rats
Xiang-lan Wei12, Ru-tang Fang3, Yong-hua Yang4, Xue-yuan Bi1, Guo-xia Ren2, A-li Luo2,Ming Zhao1* and Wei-jin Zang1*
Abstract
Liver fibrosis is a feature in the majority of chronic liver diseases and oxidative stress is considered to be its main pathogenic mechanism. Antioxidants including vitamin E, are effective in preventing liver fibrogenesis. Several plant-drived antioxidants, such as silymarin, baicalin, beicalein, quercetin, apigenin, were shown to interfere with liver fibrogenesis. The antioxidans above are polyphenols, flavonoids or structurally related compounds which are the main chemical components of Pomegranate peels and seeds, and the antioxidant activity of Pomegranate peels and seeds have been verified. Here we investigated whether the extracts of pomegranate peels (EPP) and seeds (EPS) have preventive efficacy on liver fibrosis induced by carbon tetrachloride (CCl 4 ) in rats and explored its possible mechanisms.
Source : BMC Complementary and Alternative Medicine
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Pomegranate-Date Cocktail a Day Keeps the Dr. Away
Study shows pomegranate juice/date combo fights heart disease
Glorious, red pomegranates and their Middle Eastern sister, luscious toffee-like dates, are delicious, increasingly trendy, and healthy to boot. As it turns out, when consumed together they are a winning combination in the war against heart disease. Just half a glass of pomegranate juice a day with a handful of dates can do the trick!
A team of researchers at the Technion-Israel Institute of Technology, led by Professor Michael Aviram of the Rappaport Faculty of Medicine and Rambam Medical Center, has discovered that the combination of pomegranate juice and dates along with their pits provide maximum protection against atherosclerosis (plaque buildup or hardening of the arteries), which can cause a heart attack or stroke. The findings were published in the most recent issue (March 26, 2015) of Food & Function, a journal of The Royal Society of Chemistry.
A number of risk factors are involved in the development of atherosclerosis, including cholesterol oxidation, which leads to accumulation of lipids in the arterial wall. Natural antioxidants can slow down the oxidation process in the body, and serve to reduce the risk of heart attack. For the past 25 years, Prof. Aviram and his research team have been working on isolating and researching those antioxidants, in order to keep plaque buildup at bay.
Going into the most recent study, the team was aware of the individual benefits provided by pomegranates and dates. Pomegranate juice, rich in polyphenolic antioxidants (derived from plants), has been shown to most significantly reduce oxidative stress. Dates, which are rich sources of phenolic radical scavenger antioxidants, also inhibit the oxidation of LDL (the so-called “bad cholesterol”) and stimulate the removal of cholesterol from lipid-laden arterial cells. Prof. Aviram had a hunch that since dates and pomegranate juice are composed of different phenolic antioxidants, the combination could thus prove more beneficial than the sum of its parts.
In a trial performed on arterial cells in culture, as well as in atherosclerotic mice, the Technion team found that the triple combination of pomegranate juice, date fruits and date pits did indeed provide maximum protection against the development of atherosclerosis because the combination reduced oxidative stress in the arterial wall by 33% and decreased arterial cholesterol content by 28%.
The researchers conclude that people at high risk for cardiovascular diseases, as well as healthy individuals, could benefit from consuming the combination of half a glass of pomegranate juice (4 ounces), together with 3 dates. Ideally, the pits should be ground up into a paste and eaten as well, but even without the pits, the combination is better than either fruit alone.
Source : Newswise
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Three Herbs for Cognition
Three HerbClips in this issue focus on cognition. HC 011456-496 covers a meta-analysis of bacopa (Bacopa monnieri; Scrophulariaceae).1 Bacopa has been used in Ayurvedic medicine for centuries to improve memory and intellect. Nine clinical trials were included in the meta-analysis, with a total of 231 subjects receiving bacopa and 206 subjects receiving placebo. Memory function (6 studies) and attention (7 studies) were the outcome effects. The authors conclude that bacopa may aid in improving cognitive function, particularly attention speed, but that more study is needed, especially a "head to head" trial with a proven existing medication and standardized bacopa extract. As mentioned in the previous HC News, a green tea (Camellia sinensis; Theaceae) extract was found to enhance working memory between the frontal and parietal brain regions in 12 healthy subjects (See HC 041431-496).2 The authors suggest that green tea extract could be used to treat cognitive impairments, such as dementia, by creating short-term plasticity between the brain regions. This increased connectivity could provide enhanced cognitive function for both healthy individuals as well as those with cognitive impairment. The study used a whey-based soft drink. Additionally studies with a standardized green tea extract are warranted. HC 121314-496 reviews a pilot study on pomegranate (Punica granatum; Lythraceae) supplement POMx™ (POM Wonderful; Los Angeles, California) which demonstrated that the supplement may improve postoperative cognitive dysfunction (POCD) for patients who have had heart surgery.3 Memory retention can be mildly to severely affected after heart surgery, possibly due to anesthesia or lack of oxygen/glucose to the brain. In this small study (5 active; 5 placebo), the researchers found that the pomegranate group was protected against POCD and even improved their memory retention compared to baseline.
Cognition domains include "motor functioning, attention, language, memory, executive control, vision, emotion, sensory functions, and consciousness."1 With an increased aging population, evidence of cognitive decline has also increased. Other impairments among the younger generations, such as attention deficit hyperactivity disorder, have had a notable escalation as well. Finding ways to enhance brain activity, such as word puzzles, studying new subjects, exercising to increase oxygen capacity, and some form of meditation to relax the mind, can maintain and even enhance cognitive function. Bacopa, green tea, and pomegranate, among other herbs, can also support the brain's various processes.
References
1Kongkeaw C, Dilokthornsakul P, Thanarangsarit P, Limpeanchob N, Scholfield CN. Meta-analysis of randomized controlled trials on cognitive effects of Bacopa monnieri extract. J Ethnopharmacol. 2014;151(1):528-535.
2Schmidt A, Hammann F, Wölnerhanssen B, et al. Green tea extract enhances parieto-frontal connectivity during working memory processing. Psychopharmacology. 2014; [epub ahead of print]. doi: 10.1007/s00213-014-3526-1.
3Ropacki SA, Patel SM, Hartman RE. Pomegranate supplementation protects against memory dysfunction after heart surgery: A pilot study. Evid Based Complement Alternat Med. 2013;2013:932401. doi: 10.1155/2013/932401.
Source : HerbClip-ABC
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Amelioration of Diabetes and Painful Diabetic Neuropathy by Punica granatum L. Extract and Its Spray Dried Biopolymeric Dispersions
K. Raafat1 and W. Samy2,3
1Department of Pharmaceutical Sciences, Faculty of Pharmacy, Beirut Arab University, Beirut 115020, Lebanon
2Department of Pharmaceutical Technology, Faculty of Pharmacy, Beirut Arab University, Beirut 115020, Lebanon
3Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
Abstract
Aims. To evaluate the effect of Punica granatum (universally known as pomegranate) (Pg) rind extract and its spray dried biopolymeric dispersions with casein (F1) or chitosan (F2) against Diabetes mellitus (DM) and diabetic neuropathy (DN).
Methods. We measured the acute (6 h) and subacute (8 days) effect of various doses of Pg, F1, and F2 and the active compounds on alloxan-induced DM mouse model. We evaluated DN utilizing latency tests for longer period of time (8 weeks). In addition, the in vivo antioxidant activity was assessed utilizing serum catalase level.
Results. The results proved that the highest dose levels of Pg extract, F1, F2 exerted remarkable hypoglycemic activity with 48, 52, and 40% drop in the mice glucose levels after 6 hours, respectively. The tested compounds also improved peripheral nerve function as observed from the latency tests. Bioguided fractionation suggested that gallic acid (GA) was Pg main active ingredient responsible for its actions.
Conclusion. Pg extract, F1, F2, and GA could be considered as a new therapeutic potential for the amelioration of diabetic neuropathic pain and the observed in vivo antioxidant potential may be involved in its antinociceptive effect. It is highly significant to pay attention to Pg and GA for amelioration and control of DM and its complications.
Source : Journal Complementary and Alternative Medicine
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Pomegranate
Punica granatum
Family: Lythraceae (formerly Punicaceae)
by Gayle Engels, Josef Brinckmann - HerbalGram. 2013; American Botanical Council
INTRODUCTION
Pomegranate is a deciduous shrub or small tree, sometimes thorny, growing to 16 feet (five meters) tall.1-3 It has oblong, shiny, leathery leaves up to three inches (eight centimeters) in length, and the scarlet funnel-shaped flower has five-to-eight rumpled petals with a matching calyx.1-5 The fruit is a large berry with tough, leathery skin (called a husk, rind, or pericarp), with a persistent calyx and fleshy pulp enclosing edible seeds.2,3,5
The pomegranate is believed to have originated in Persia (modern-day Iran), Afghanistan, Pakistan (particularly the province of Baluchistan),6 and perhaps northern India. It was spread throughout the Middle East to Southeastern Europe around the Mediterranean, to China, North Africa, and eventually to warm regions of the New World.2,3,7 In India, P. granatum is found in the wild only in the Western Himalayan regions comprising the states of Jammu, Kashmir, Himachal Pradesh, and Uttarakhand.8 To the northwest of Iran — in Armenia, Azerbaijan, and Georgia — there are wild pomegranate groves found outside of abandoned ancient settlements.9 Naturalized in Western China, it was probably introduced there from Central Asia during the Han Dynasty (207 BCE to 220 CE).10
The pericarp and pulp of the fruit as well as the root bark are used either culinarily or medicinally.1-3
HISTORY AND CULTURAL SIGNIFICANCE
Pomegranate is one of only two species in the Punica genus; it was the sole genus in the Punicaceae family prior to its reclassification in Lythraceae.7 The generic epithet, Punica, is the feminized Latin name for Carthage, originally from the Greek Phoinix referring to the Phoenician settlers around Carthage. The specific epithet, granatum, means seedy or grainy. Prior to its renaming by Linnaeus in the 18th century, the plant was known as Malum punicum, the apple of Carthage.7
In the 12th century, the Anglo-Norman name for the fruit, pome gernate, became pume grenate in Old French and eventually pomme grenade in Modern French.11 By the 15th century, hand-thrown weapons made of cast iron and filled with gunpowder had been invented and called grenades. To this day, opening a grenade exposes tiny balls of shrapnel that resemble a pomegranate’s seeds.
The name for pomegranate in both Arabic (rumman) and Hebrew (rimmon) means “fruit of paradise,” and it has been a symbol of love since ancient times.1,7 It was mentioned multiple times in the Biblical Song of Songs, also known as the Song of Solomon (Solomon 4:3, 4:13, 6:7, 6:11, 7:12, and 8:2); it played a large role in the Greek myth of Persephone; and it was associated commonly with Aphrodite and Dionysius.1,7 Even Shakespeare made note of the pomegranate tree in Romeo and Juliet.12
Pomegranate has been affiliated with abundance, blessings, fertility, immortality, invincibility, posterity, prosperity, and the endurance of marriage.1,7 While its multitude of seeds might explain why pomegranate is linked with fertility, it is interesting to note that in one version of the Greek myth, Persephone, daughter of the fertility goddess, Demeter, disobeyed her father, Zeus, and ate some pomegranate seeds while in the underworld, causing Demeter’s distress and the onset of autumn and winter in the world above (i.e., an interruption of fertility).13 Perhaps not coincidentally, contraception was one of the earliest reported medicinal uses of pomegranate. The Greek physician Soranus recorded five prescriptions for either oral contraceptives or vaginal suppositories made from pomegranate seeds or rinds.14 Hippocrates (468-377 BCE), Dioscorides (40-90 CE), and Ibn Sina (Avicenna, 980-1037 CE) also described the contraceptive use of pomegranate seeds or rinds.14 By the Middle Ages, though, pomegranates had disappeared from medical writings for this purpose.
Historically, pomegranate has been significant in several cultures for its food and medicinal uses, as well as for its spiritual and artistic symbolism. The fruit was an extremely useful way of transporting liquid when traveling through the desert.7 In addition to its juice, the arils (juicy pulp covering the seeds) were and are a distinctive component of certain Middle Eastern dishes: fesenjan (lamb or chicken stew with walnuts and pomegranates), khosaf al-rumman (pomegranate with nuts and orange flower syrup), and pomegranate khoresh (stew), to name a few.
Pomegranate is mentioned as a remedy for roundworm in the Ebers Papyrus (the oldest preserved medical document, from Egypt, ca. 1500 BCE).15 Hippocrates used pomegranate seed extracts for numerous ailments including skin and eye inflammation and as a digestive aid, while Dioscorides recommended various pomegranate parts, sometimes in combination with other ingredients, for stomach ailments, mouth and genital sores, gum disorders and loose teeth, as well as for expelling parasites.7 Treatment of bronchitis, diabetes, diarrhea, hemorrhaging, leprosy, and snakebites are all traditional uses of pomegranate.7 Both the dried fruit rind and pulp have been used commonly for upset stomachs and diarrhea, prepared as infusions (teas) or tinctures (alcoholic extractions).3
Most parts of the pomegranate — including the flower, fruit rind, leaf, dried seed and fresh seed, root bark or trunk bark, fresh fruit and preparations thereof (e.g., juice) — have defined therapeutic applications in traditional medicine systems such as Ayurveda, Siddha, gSo-ba Rig-pa (Traditional Bhutanese), Sowa-Rigpa (Traditional Tibetan), Traditional Chinese Medicine (TCM), Traditional Iranian Medicine, Unani, and European Homoeopathy. The fresh fruit and fruit juice are used widely as foods and the juice also is used as a source of polyphenols. Essential oils, extracts, and waters of various plant parts, as well as isolates and derivatives such as pomegranate fruit peel extract octenylsuccinate, seed oil hydroxyphenethyl esters, and sterols obtained from the seed oil, are used as cosmetic ingredients.
The flower, fruit, fruit rind, and seed of P. granatum L. var. granatum are used specifically in Ayurveda, Siddha, Sowa-Rigpa (Amchi), and Unani systems of traditional medicine in India, and in regional Indian folk medicines. The materials of commerce are obtained from both cultivated and wild-collected sources. The flower of P. granatum L. var. nana Pers. (cultivated) is used in Indian folk medicine.16
In TCM, pomegranate husk/rind (called shi liu pi) is used to treat diarrhea, dysentery, rectal prolapse, spermatorrhea and premature ejaculation, uterine bleeding, vaginal discharge due to kidney instability, and to kill and expel parasites.17 It also is used topically for ringworm and in combination with other herbs for the conditions mentioned above.17
The dried ripe fruit (with seeds removed) is used in Tibetan medicine to restore weak digestive heat, to correct indigestion and loss of appetite, and for all forms of cold diseases and disorders of the lungs.18 In the Bhutanese system of medicine, it functions as a primary component of herbal combinations in pill form indicated for treatment of indigestion and diarrhea.19
According to the World Health Organization (WHO) monograph Cortex Granati, therapeutic uses described in pharmacopeias and well-established documents for preparations of the root bark and/or trunk bark (aqueous decoction and/or hydroalcoholic fluidextract 1:1) include treatment of diarrhea and intestinal parasites. In systems of traditional medicine, preparations of the bark are used for treatment of dyspepsia, sore throat, menorrhagia (heavy menstrual bleeding), leucorrhoea (vaginal discharge), and ulcers.20
CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES
In the Ayurvedic system of medicine (recognized in India, Bangladesh, Bhutan, Malaysia, Nepal, and Sri Lanka), the therapeutic uses of the different plant parts are similar to what has been described previously, with some notable exceptions:
The fresh fruit juice of pomegranate at a dose of 15-30 mL is used in formulations for treating conditions including bleeding disorder (hemorrhagic diseases, i.e., bleeding with stools or from nose, excessive bleeding during menstruation, or bleeding from any other part of the body without injury), burning sensation in the eyes, chest, palm and/or soles of feet (e.g., diabetic neuropathy); cough, diarrhea, fever, loss of taste sensation, rheumatoid arthritis, and thirst.21
The dried and powdered fruit rind at a dose of 3-6 g is indicated for bleeding disorder and disorders of blood, burning sensation, cough, diarrhea, dysentery, fever, halitosis (bad breath), hyperacidity of the stomach, loss of taste sensation, and throat diseases.21
The dried leaf at a dose of 5-10 g is indicated for treatment of bleeding disorder, cough, diarrhea, digestive impairment, dysentery, fever, helminthiasis (worm infestation), loss of taste sensation, and stomatitis (inflamed and sore mouth).21
Dried powdered pomegranate seeds are used in Ayurvedic medicine at a recommended dose of 5-10 g for treatment of burning sensation, fever, and morbid thirst.22
In the Unani system of medicine (recognized in Bangladesh, India, Malaysia, Pakistan, and Sri Lanka), various pomegranate plant parts also have different therapeutic indications usually occurring as components of complex formulations:
The dried leaf at a dose of 5-10 g is used for diarrhea, chest pain, palpitations, spermatorrhea (involuntary discharge of semen without orgasm), stomatitis, and vomiting.23
The dried seed at a dose of 5-10 g is used for treatment of cardiac weakness, chest pain, jaundice, as an emetic (to induce vomiting), and as a purgative (for intestinal evacuation in certain diseases).24
The fresh seed prepared as juice at a dose of 25-60 mL is used for treating anemia, burning in the chest, general weakness, jaundice, nausea and vomiting, and polydipsia (chronic excessive thirst).25
In Canada, extract of pomegranate fruit and/or aril is classified as a medicinal ingredient of licensed natural health products (NHPs) requiring pre-marketing authorization from the Natural Health Products Directorate (NHPD) and manufacture in compliance with NHP Good Manufacturing Practices (GMPs). “Provides antioxidants” is the NHPD-authorized use for the extract.26
Several pomegranate ingredients also are permitted for use as non-medicinal components of licensed NHPs for specific purposes, including “concentrated pomegranate juice” as a flavor enhancer, “Punica granatum fruit extract” as a fragrance ingredient in topical application NHPs, and various extracts of the pericarp and/or seed and fixed oil of the seed as skin-conditioning agents.27
In the United States, essential oils, solvent-free extracted oleoresins, and natural extractives of pomegranate are classified by the Food and Drug Administration (FDA) as Generally Recognized as Safe (GRAS) for use in conventional food products.28 For use as a source of polyphenols, a pomegranate fruit juice monograph is under development by the United States Pharmacopeial Convention for inclusion in the forthcoming ninth edition of the Food Chemicals Codex.29
Pomegranate plant parts also are permitted for use as dietary supplement components, requiring FDA notification within 30 days of product marketing (if a “structure-function” claim is made) and product manufacturing according to dietary supplement GMPs.
In the European Union, the present regulatory status for the use of fruit oil and rind of P. granatum in conventional food products is uncertain. There has been a request made to determine if the fruit oil and rind will require authorization under the Novel Food Regulation.30
Additionally, the 2013 European Pharmacopoeia Commission work program is developing a new quality standards monograph for the homeopathic preparation “Punica granatum ad praeparationes homoeopathicas.”31
There are nearly 30 different pomegranate ingredients authorized for use in cosmetic products by the European Commission Health and Consumers Directorate — too many to list and discuss in this review. Some examples include the fruit juice for masking (reduces or inhibits the basic odor or taste of the product) and skin-conditioning functions. Fruit water (an aqueous solution of the steam distillates obtained from the fruit) is authorized for functions including astringent (contracts the skin), flavoring, tonic (produces a feeling of well-being on skin and hair), and masking. “Punica Granatum Sterols” (a mixture of sterols obtained from the fixed oil of the seeds) is used for skin- and hair-conditioning functions.32
Corresponding to some of the authorized uses discussed in this article, quality standards monographs are available for specifying and testing the various plant parts of P. granatum (e.g., fresh fruit, dried fruit rind, dried leaf, dried seed, fresh seed, root bark or trunk bark) published in the Ayurvedic Pharmacopoeia of India (Vol. 2, 1999, and Vol. 4, 2004),21-22 Unani Pharmacopoeia of India (Vol. 2, 2007; Vol. 4, 2007; and Vol. 6, 2009),23-25 and WHO monographs (Vol. 4, 2009).20
For quality control in food applications there are also pomegranate standards, specifications, and test methods available from the East African Community (East African Standard CD/K/102:2010),33 The Food and Agriculture Organization (FAO) of the United Nations (Codex Standard 310-2013),34 the Government of India Ministry of Agriculture (AGMARK Grading and Marking Rules 2004),35 and the International Organization for Standardization (ISO 23393:2006).36
MODERN RESEARCH
Pomegranate is a relatively good source of several vitamins and minerals such as vitamin C, thiamin, riboflavin, niacin, calcium, iron, and magnesium.37 All plant parts contain polyphenols; the pericarp (both the peel and the membrane) has the largest concentration.5 Polyphenols are responsible for the astringency of the juice and comprise two major classes of compounds — hydrolysable tannins and flavonoids — which are believed to be responsible for pomegranate’s beneficial actions. Numerous in vitro studies have documented the strong antioxidant properties of pomegranate.5
In 2012, a randomized, placebo-controlled, parallel group study examined the effect of pomegranate juice on pulse wave velocity (PWV), a measure of arterial stiffness that is a predictor of future cardiovascular events.38 Healthy participants (n=51) were randomly assigned to consume 330 ml/day pomegranate juice (PJ; Pomepure®, extracted using an industrial centrifugal juice extractor, The Pure Juice Company Ltd; Twickenham, UK) or placebo beverage for four weeks. Measurements were made at baseline and four weeks. While mean arterial pressure and diastolic and systolic blood pressure all decreased in the PJ group, PWV did not. The authors state numerous limitations to the study, among them the fact that subjects’ compliance was not confirmed, dietary intake was not assessed, the intervention period (four weeks) was short, and the pomegranate juice was not profiled to check for adulteration, although its total antioxidant capacity and content of phenolic compounds and potassium were consistent with reported values.
A study published in 2012 investigated the results of a randomized, placebo-controlled, double-blind clinical trial wherein 101 chronic hemodialysis (HD) patients received, during each dialysis, 100 cc PJ (0.7 mmol/100 cc juice polyphenols, Naturafood Ltd; Givat Hen, Israel) or matching placebo, three times/week for one year.39 HD patients frequently experience increased systemic inflammation and oxidative stress leading to atherosclerosis. The PJ group experienced reduced inflammation biomarker levels and protein and lipid oxidation. PJ intake also resulted in fewer second hospitalizations due to infections and improvement in the atherosclerotic process in 25% of patients. The beneficial effects disappeared three months after the study ended. The authors state that the findings are novel and should be replicated and validated in order to make PJ intake a part of dialysis therapy.
A number of human clinical studies have been conducted investigating the efficacy in cardiovascular health of POM Wonderful® Pomegranate Juice (POM; proprietary product made exclusively from the whole fruits of the ‘Wonderful’ variety, POM Wonderful, LLC; Los Angeles, CA). In a small, open-label, parallel group clinical trial in 2004 that ran for one year, 19 patients with carotid artery stenosis (CAS, hardening of the carotid artery; 70-90% occlusion) were randomly assigned to take 50 ml/day POM or no treatment.40 The group taking POM experienced a decrease in the properties that lead to hardening of the arteries, such as carotid thickness, lowered systolic blood pressure, and platelet aggregation. However, the two groups were not treated equally; there was no placebo for the control group, and the POM group received more interventions — such as blood draws and carotid ultrasounds — than the control group.
A three-month, open-label, control group comparison published in 2006 was conducted with 10 non-insulin-dependent diabetics and 10 healthy age-matched controls.41 Each participant was given 50 ml of concentrated POM diluted 1:5 with water to equal eight oz./day. In the diabetic group, serum C-peptide levels were reduced by 23% after POM consumption. Results also indicated that POM had a beneficial effect on oxidative stress experienced by diabetics. Additionally, POM consumption did not worsen the diabetic parameters, as the authors had feared.
A 2005 randomized, double-blind, placebo-controlled clinical study investigated the effect PJ had on myocardial perfusion in patients with coronary heart disease (CHD) and myocardial ischemia.42 Over three months, 45 patients with stable CHD ingested 240 ml (eight oz.) POM per day or a modified sports drink placebo. At baseline and at three months, patients underwent treadmill or pharmacologic stress testing. Of the 39 individuals who completed the regimen and underwent testing, stress-induced ischemia decreased in the POM group (by 17% compared to baseline) and increased by 18% in the control group.
In a small open-label study in 2001, 10 hypertensive patients (seven male, three female, all nonsmokers, two diabetic, and two hyper lipidemic) consumed 50 ml POM concentrate per day for two weeks to see if it had an effect on hypertension and angiotensin converting enzyme (ACE).43 Blood pressure and ACE activity were measured before and after POM intake. Juice consumption resulted in a small (5%) but significant reduction of systolic blood pressure and a significant (36%) decrease in ACE activity in seven of the 10 patients.
An 18-month, multi-center, randomized, double-blinded, two-dose human clinical trial in 2013 investigated the ability of a pomegranate extract (POMx) to increase prostate-specific antigen doubling time (PSADT) in men with rising PSA and no metastases.44 PSADT is a predictor of metastasis-free survival and overall survival in patients who have undergone primary therapy for localized prostate cancer. In this study, 104 patients were randomly assigned to receive three capsules of POMx (1000 mg/capsule, polyphenol extract, comparable to about eight oz. pomegranate juice, POM Wonderful, LLC) or one capsule POMx plus two placebo capsules (to equal three capsules). Both low-dose and high-dose groups experienced ≥ (greater than or equal to) six-month increases in PSADT without adverse effects. The authors state that the significance of the study is unclear and that placebo-controlled studies are needed in this patient population.
In a 2006 phase II, open-label, single-arm clinical trial, 46 men with recurrent prostate cancer and rising PSA took eight oz./day of POM until their disease progressed.45 PSA values were measured at least three times over six months prior to the beginning of the treatment, and PSA values as well as blood and urine for laboratory studies were taken at three-month intervals. A positive response was defined as a ≥ 50% decrease in measured serum PSA levels, and progressive disease was defined as either a > 100% increase in PSA compared with the best response observed or any documentation of metastatic or recurrent disease. Treatment with POM significantly lengthened the PSADT in the patients; mean PSADT increased from 15 months at baseline to 54 months after treatment; and seven subjects experienced decreased PSA over time.
A few studies have investigated the potential of pomegranate to help with the control of dental plaque. In one study published in 2009, 32 healthy men and women with good oral hygiene habits in a randomized, single-blinded, controlled study were assigned to rinse their mouths three times daily (one minute per rinse) with 35 ml of a pomegranate extract-containing aqueous solution (Pomella® Extract; standardized to contain 30% punicalagins, Verdure Sciences; Noblesville, IN) or placebo rinse for four weeks.46 Saliva samples revealed that rinsing with a flavonoid-rich pomegranate extract reduced total protein, which can correlate with lowered plaque formation, as well as reductions in cell injury indicators, sucrose degradation, and possible oral oxidant stress, as well as increased radical scavenging capacity.
In an earlier study, 60 subjects were divided into three groups of 20 who, following 24 hours of no dental hygiene, had dental plaque samples taken, then rinsed with one of three mouthwashes.47 The mouthwashes were chlorhexidine gluconate (0.12% PerioGard®, Kolynos of Brazil; São Paulo, Brazil [now Colgate-Palmolive; New York]), or hydroalcoholic extract (HAE, 1:1 by volume) of pomegranate (50-60 mg/mL)(Federal University of Ceará, Fortaleza, Brazil), or a control of just the hydroalcoholic extract. The subjects in the HAE and PerioGard groups showed a positive response, i.e., a reduction in oral bacteria as measured by colony forming units (CFUs) after rinsing. The HAE group had an 83.5% reduction and the PerioGard group had a 79.0% reduction in CFUs. The control group had a non-significant reduction of 11.3%. The authors speculate that the equivalent effect of HAE of pomegranate to chlorhexidine may be due to the hydrolysable tannins in pomegranate, particularly punicalagin, but that further studies are needed to identify the active constituents.
FUTURE OUTLOOK
According to the Iranian regional standard for pomegranate, “In addition to Iran which has the highest area under cultivation, highest production, and is the number one exporter, other countries including Turkey, Afghanistan, Pakistan, India, Armenia, Georgia, Tajikistan, Jordan, Egypt, Italy, Tunisia, Azerbaijan, Libya, Lebanon, Sudan, Myanmar, Bangladesh, Mauritania, Morocco, Cyprus, Spain, Greece, France, China, Japan, and the US are among the countries which have areas under pomegranate cultivation.However, among these countries, India, the Central Asian Republics, Upper Caucuses, and Spain have the highest area under cultivation and varietals diversity. Consumption of pomegranate in Iran is estimated to be on average between 7-8 kg per person per year.”48
Total worldwide production of pomegranate is approximately 1.5-to-two metric tons (MT), with Iran and India producing most of the global supply. For the juice market, Iran and India together account for about 95% of concentrate production.49
In the United States, most of the pomegranate crop is grown in California. Canada is the number-one export destination for US-grown pomegranates, followed by Korea, Taiwan, Australia, Japan, Mexico, and Russia.50 In 2011, California had an estimated 30,000 acres (12,140 hectares) of pomegranates under cultivation.51
Pomegranate dietary supplement sales were ranked 42nd in the US food, drug, and mass market channel in 2012 with $2,558,509 in sales, down 25.4% from the previous year.52 In the natural food channel (not including Whole Foods Market), pomegranate ranked 66th with sales of $1,062,539, down 3.4% from 2011.53 (These statistics do not include the sales of pomegranate juices, which are significantly higher.) In Canada, at the time of this writing, there were 188 licensed NHPs containing pomegranate as a medicinal ingredient and another 70 NHPs containing some form of pomegranate as a non-medicinal ingredient.54
The United States Agency for International Development is currently working with Afghanistan to increase its pomegranate production and exportation. Trade relationships were established in 2011 among Kandahar pomegranate traders and India, Pakistan, and Europe, ultimately leading to exports of more than 2,700 MTs of pomegranates from Afghanistan.55 In the year ending May 2012, Innova Market Insights stated that new products featuring pomegranate increased 15% worldwide from the previous year.56
—Gayle Engels and Josef Brinckmann
Source : American Botanical Council - Herbalgram
Link to Source + References
Preventive and Prophylactic Mechanisms of Action of Pomegranate Bioactive Constituents
Monica Viladomiu,1,2 Raquel Hontecillas,1,2 Pinyi Lu,1,2 and Josep Bassaganya-Riera1,2,3
1Nutritional Immunology and Molecular Medicine Laboratory, Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, VA 24060, USA
2Center for Modeling Immunity to Enteric Pathogens, Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, VA 24060, USA
3Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA
Abstract
Pomegranate fruit presents strong anti-inflammatory, antioxidant, antiobesity, and antitumoral properties, thus leading to an increased popularity as a functional food and nutraceutical source since ancient times. It can be divided into three parts: seeds, peel, and juice, all of which seem to have medicinal benefits. Several studies investigate its bioactive components as a means to associate them with a specific beneficial effect and develop future products and therapeutic applications. Many beneficial effects are related to the presence of ellagic acid, ellagitannins (including punicalagins), punicic acid and other fatty acids, flavonoids, anthocyanidins, anthocyanins, estrogenic flavonols, and flavones, which seem to be its most therapeutically beneficial components. However, the synergistic action of the pomegranate constituents appears to be superior when compared to individual constituents. Promising results have been obtained for the treatment of certain diseases including obesity, insulin resistance, intestinal inflammation, and cancer. Although moderate consumption of pomegranate does not result in adverse effects, future studies are needed to assess safety and potential interactions with drugs that may alter the bioavailability of bioactive constituents of pomegranate as well as drugs. The aim of this review is to summarize the health effects and mechanisms of action of pomegranate extracts in chronic inflammatory diseases.
Conclusions
There is strong evidence that pomegranate elicits ameliorating health effects in several diseases. When considering the pomegranate therapeutic studies along with the research investigating the bioavailability of its compounds, one can conclude that pomegranate’s bioactive constituents can be absorbed and exert their biological activity. However, this fruit contains hundreds of different bioactive compounds, thus requiring a better understanding of the beneficial effects elicited by each compound and not the fruit as a whole. Moreover, some studies report that the administration of combinations of bioactive compounds has increased activity when compared to single compounds. Therefore, there is a need to further study possible synergistic effects between pomegranate’s bioactive components through isobolograms in the context of ligand-binding assays and factorial designs in animal models. In this regard, the integration of computational and experimental nutritional immunology research represents a cost, and time-efficient approach for the discovery of novel interactions and mechanisms underlying such activities. Many of the pomegranate’s beneficial effects have been widely related to the presence of ellagic acid and ellagitannins, especially punicalagins, punicalins, and gallagic acid. However, anthocyanins as well as pomegranate’s distinct and unique fatty acid profile also contribute to the reported health effects. Interestingly, several effects of pomegranate are mediated by the activation of PPAR pathways by conjugated trienes derived from seed oil. Some studies suggest that pomegranate metabolites may also contribute to its therapeutic effects along with the components of the fruit. In line with these findings, pomegranate has been suggested to stimulate probiotic bacteria thus enhancing their beneficial effects and fighting bacterial infections. Therefore, gut microflora seems to be important for pomegranate therapeutic activities. Pomegranate is safe at high doses in humans. So far, pomegranate has been shown to elicit beneficial effects for the treatment of obesity, diabetes, inflammation-related diseases such as IBD and NEC, and several types of cancer, as well as cardiovascular complications. However, there is still a need to identify individual active ingredients of pomegranate as well as further explore synergistic preventive effects in laboratory, animal models, and human clinical studies.
Source : Journal Evidence Based Complementary and Alternative Medicine
Link to Full Article
A REVIEW ON THE ANTI-INFLAMMATORY ACTIVITY OF POMEGRANATE IN THE GASTRO-INTESTINAL TRACT
1Elisa Colombo, 1Enrico Sangiovanni, 1, 2Mario Dell'Agli*
1Department of Pharmacological and Biomolecular Sciences, and 2Research Centre for
Characterization and Safe Use of Natural Compounds-G. Galli, Università degli Studi di Milano, Via Balzaretti 9, Milano, Italy
Abstract
PG is used in the traditional medicine of different Asian cultures for the treatment of a variety of ailments. The biological activity of pomegranate has been widely investigated, including in vitro, in vivo and clinical studies. The beneficial effects are mostly the cardiovascular protective role, neuroprotective activity, hypoglycemic effect and anticancer properties, in particular against prostate, colon and breast cancer; the anticancer effect are limited only to in vitro and animal studies. The gastrointestinal tract represents an important barrier between the human hosts and microbial populations. One potential consequence of host-microbial interactions is the development of mucosal inflammation, which can lead to gastritis and ulcer. Gastritis defined as inflammation of the gastric mucosa can be caused by endogenous and exogenous factors including acid, pepsin, stress, and noxious agents such as alcohol, non-steroidal anti-inflammatory drugs, Helicobacter pylori infection and smoking. Conversely, inflammatory bowel diseases, among which Crohn’s disease and ulcerative colitis, are the most common inflammatory-related diseases in the gut; inflammatory bowel diseases occur in response to genetic or environmental factors and are characterized by the uncontrolled response of the intestinal immune system against the normal enteric microflora, leading to abdominal pain and chronic diarrhoea.
Although the anti-inflammatory properties of pomegranate and its major components have been widely described in the literature and some papers have been published at this regard, surprisingly this effect has not been reviewed till now. The aim of the present review is to summarize the evidence for or against the efficacy of pomegranate for coping inflammatory conditions of the gastro-intestinal tract.
The review has been organized in three parts: 1) a first one is devoted to the modifications of pomegranate active compounds in the gastro-intestinal tract, with particular attention to the intestinal metabolites; 2) a second one considering the literature regarding the anti-inflammatory effect of pomegranate and individual compounds at gastric level; 3) a third part considering the antiinflammatory effect of pomegranate and individual compounds in the gut, taking into account also the main metabolites which are formed by microbial biotransformation after pomegranate consumption. In vivo studies performed on the whole fruit or juice, peel and flowers demonstrate high anti-ulcer effect in a variety of animal models. Ellagic acid was found to be the main responsible for this effect, although other individual ellagitannins, which have not yet been studied, could contribute to the biological activity of the mixture.Different preparations of pomegranate, including extracts from peels, flowers, seeds, and juice, show a significant anti-inflammatory activity in the gut. Oil derived from PG seeds and its major 3 component punicic acid, inhibits the expression of pro-inflammatory cytokines through the modulation of PPAR-γ and δ, whereas pomegranate peel extracts, and the pure compounds
punicalagins and ellagic acid, inhibit the expression and secretion of several inflammatory mediators. The inhibitory effect is ascribed to the inhibition of the NF-κB pathway and involves the MAPKs system as well. Between urolithins, urolithins A has been shown to possess a significant antiinflammatory activity both in vitro and in vivo, thus suggesting that this compound, and not its
precursor EA, could be the main responsible for the anti-inflammatory properties observed with PG extracts in the gut. Unfortunately, no clinical studies addressing the anti-inflammatory activity of PG at the gastro-intestinal level have been found, thus suggesting that future clinical studies on antiinflammatory activity at the gastrointestinal tract are necessary to clarify the beneficial effects of pomegranate for human health.
Conclusion
Few in vitro studies have been performed with PG peel extracts to evaluate anti H. pylori activity. These extracts are able to reduce significantly the growth of this pathogen, which is considered the aetiological agent mainly responsible for human gastritis.
In vivo studies performed on the whole fruit or juice, peel and flowers, demonstrate high anti-ulcer effect in a variety of animal models. EA was found to be the main responsible for this effect, although other individual ETs, which have not yet been studied, could contribute to the biological activity of the mixture. With the exception of EA, the effect of the pure compounds at the gastric
level was not investigated; this should be carefully considered for the future studies, since these molecules appear to be unmodified at the gastric level. Conversely, the positive effect of EA has been widely demonstrated, and the effect is corroborated by other studies performed on other plants: ethanolic extract from Ficus glomerata fruit (FGE) contained 0.36% w/w of EA and showed significant dose-dependent anti-ulcerogenic in different models of induced gastritis (pylorus ligation, ethanol and cold stress) [69]; moreover, the hydroalcoholic extract of Anogeissus latifolia (50% alcohol) containing 0.25% w/w of EA, has been shown to possess gastro-protective activity [70] due to the presence of EA. In addition, methanol stem bark extract of Lafoensia pacari containing 23.4% 19 of EA showed gastro-protective and ulcer healing effects in animal models strictly associated to the
presence of great amounts of EA in the extract [71], and an improvement of the gastric symptoms in patients with H. pylori gastritis was observed [72]. The mechanism of action by which EA shows anti-ulcer activity is partially attributed to the inhibitory effect on the gastric H+, K+-ATPase, in addition to the anti-H. pylori activity [38].
Unfortunately, no clinical studies coping with the anti-inflammatory activity of PG at the gastric level have been found, thus suggesting that the effect of the extracts and individual compounds in this area need to be elucidated. In particular, it is necessary to draw clinical trials considering the effects of PG extracts in patients with H. pylori-induced gastritis, alone or in combination with antibiotics. Different preparations of PG, including extracts from peels, flowers, seeds, in addition to the juice, show a significant anti-inflammatory activity in the gut. From all the studies taken into consideration in the present review, some conclusions can be drawn. First of all, the pure compounds occurring in PG fruits seem to act through different pathways. Oil derived from PG seeds and its major component PuA, could inhibit the expression of pro-inflammatory cytokines (such as IL-6, IL-8, IL-23, IL-12 and TNF-α) through the modulation of PPAR-γ and δ. This is not true for PG peel extracts, as well as their components punicalagins and EA, since they do not show any effect on PPAR signalling; conversely, the main effect is due to the inhibition of the expression and secretion of several inflammatory mediators (i.e. IL-6, IL-8, MCP-1, iNOS, COX-2 and PGE2). The inhibitory effect is ascribed to the inhibition of the NF-κB pathway and involves the MAPKs system as well. This effect was confirmed both in vitro and in vivo for the extracts and the pure compound punicalagin, while contradictory results were found for EA, since it seems to be effective also in studies performed in vivo. This might be explained considering the metabolic fate of PG phenolic compounds. In fact, different studies demonstrate a strong interaction between gut microbiota and PG polyphenols (i.e EA) that are metabolized by intestinal microflora to urolithins. These metabolites themselves could modulate gut microbiota, enhancing the growth of beneficial strains in spite of pathogenic ones. Between urolithins, urolithins A has been shown to possess a significant antiinflammatory activity both in vitro and in vivo, thus suggesting that this compound, and not its precursor EA, could be the main responsible for the anti-inflammatory properties observed with PG extracts in the gut. However it has been also showed that the inflammatory status alters the composition of intestinal microbiota, changing its metabolic capacity and the bioavailability of phenolic compounds [60]. This statement is corroborated by observation that, after consumption of PG extract, the phenolic profile of faeces obtained from healthy and DSS-fed rats is deeply changed: in normal conditions EA and punicalagin are completely metabolized to urolithins A, whereas in inflammatory conditions they can be found unmodified in the colon [60]. This suggests that 20 biological effects of urolithins, and consequently PG, could be strictly related to the composition of individual microbiota and to the intestinal inflammatory status. For this reason, although the studies reported herein seem to recommend PG consumption to prevent or treat gastro-intestinal inflammation, future clinical studies on anti-inflammatory activity at the gastrointestinal tract are necessary to clarify the beneficial effects of PG for human health.
Source : Evidence Based Complementary and Alternative Medicine
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Pomegranate extract induces apoptosis in human prostate cancer cells by modulation of the IGF-IGFBP axis
Satomi Koyama,1 Laura J Cobb,1 Hemal H Mehta,1 Navindra P. Seeram,2 David Heber,2 Allan J. Pantuck,3 and Pinchas Cohen11
Division of Pediatric Endocrinology, Mattel Children's Hospital, David Geffen School of Medicine, University of California, Los Angeles
2Center for Human Nutrition, David Geffen School of Medicine, UCLA
3 Department of Urology, David Geffen School of Medicine, UCLA
Abstract
The IGF axis is critical for the regulation of apoptosis in many human cancer cell lines. Recently, potent anti-tumorigenic effects of pomegranate juice and extracts have been reported. Consequently, pomegranate has potential not only as a treatment but also as a preventative measure against certain types of cancer, including prostate. In this study, we investigated the relationship between pomegranate-induced apoptosis in human prostate cancer cells and the IGF/IGFBP system. Treatment of LAPC4 prostate cancer cells with 10 μg/ml POMx, a highly potent pomegranate extract prepared from skin and arils minus seeds and standardized to ellagitannin content (37% punicalagins by HPLC), resulted in inhibition of cell proliferation and induction of apoptosis. Interestingly, co-treatment with POMx and IGFBP-3 revealed synergistic stimulation of apoptosis and additive inhibition of cell growth. Western blot analysis revealed that treatment with POMx or POMx/IGFBP-3 combination resulted in increased JNK phosphorylation, and decreased Akt and mTOR activation, consistent with a growth inhibitory, pro-apoptotic function. We also investigated the relationship between IGF-1 and pomegranate-induced apoptosis in 22RV1 prostate cancer cells. Co-treatment with 100 ng/ml IGF-1 completely blocked apoptosis induction by POMx. In contrast, IGF-I failed to inhibit POMx-induced apoptosis in R- cells, suggesting the importance of IGF-IR. POMx-treatment decreased Igf1 mRNA expression in a dose-dependent manner indicating that its actions also involve tumor-specific suppression of IGF-1. These studies revealed novel interactions between the IGF system and pomegranate-induced apoptosis.
In conclusion, these studies reveal novel interactions between the IGF system and pomegranate-induced apoptosis, and suggest that pomegranate products modulate the tumor production and responsiveness to IGFs and the IGFBPs. As IGFBP-3 is currently being tested in humans as a treatment for prostate cancer and pomegranate supplements are becoming popular as adjuvant nutritional treatments for this disease, we propose that these agents may emerge as useful in the management of prostate cancer.
Source : Growth Horm IGF Res. 2010 February; 20(1): 55.
Link to Full Article
Pomegranate extract inhibits androgen-independent prostate cancer growth through a nuclear factor-κB-dependent mechanism
Matthew B. Rettig 25,David Heber4, Jiabin An5,Navindra P. Seeram4,Jian Y. Rao3, Huiren Liu1,Tobias Klatte2,Arie Belldegrun2,Aune Moro4,Susanne M. Henning4, Deqiong Mo5,William J. Aronson26 and Allan Pantuck2
Abstract
Constitutive nuclear factor-κB (NF-κB) activation is observed in androgen-independent prostate cancer and represents a predictor for biochemical recurrence after radical prostatectomy. Dietary agents such as pomegranate extract (PE) have received increasing attention as potential agents to prevent the onset or progression of many malignancies, including prostate cancer. Here, we show that PE inhibited NF-κB and cell viability of prostate cancer cell lines in a dose-dependent fashion in vitro. Importantly, maximal PE-induced apoptosis was dependent on PE-mediated NF-κB blockade. In the LAPC4 xenograft model, PE delayed the emergence of LAPC4 androgen-independent xenografts in castrated mice through an inhibition of proliferation and induction of apoptosis. Moreover, the observed increase in NF-κB activity during the transition from androgen dependence to androgen independence in the LAPC4 xenograft model was abrogated by PE. Our study represents the first description of PE as a promising dietary agent for the prevention of the emergence of androgen independence that is driven in part by heightened NF-κB activity.
.....Extending the duration of the androgen-dependent state could potentially prolong life expectancy of prostate cancer patients and delay or prevent the need for additional hormonal therapy or chemotherapy. In this regard, our finding that PE delayed the growth and emergence of androgen independence in our xenograft model may be particularly germane. Of importance, our group showed previously that dietary fat reduction delayed the emergence of androgen independence and prolonged survival using a similar xenograft model (36). Future research will focus on potential additive and/or synergistic effects of combining a low-fat diet with PE. Based on our results, we propose that PJ could have potential as a dietary agent to prevent the emergence of androgen independence and suggest that this may be a high priority area for future clinical investigation.
Source : Mol Cancer Ther 2008;7(9):2662–71
Link to Full Article
Potential Therapeutic Effects of Pomegranate Juice on Prostate Cancer
Reviewed: Pantuck AJ, Leppert JT, Zomorodian N, et al. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin Cancer Res. 2006;12(13):4018-4026.
Although the 5-year survival rate for men with prostate cancer has increased dramatically, from a 67% survival rate in the 1970s to over 90% in recent years when caught and treated early, prostate cancer is still the most common cancer (excluding skin cancer) and the second leading cause of cancer-related death in men in the United States.
Primary management of the disease for most men is either radical surgery or radiation therapy. In a significant number of men, the disease metastasizes. According to the authors, patients who have undergone primary management to cure the disease and who have progressive elevation of their prostate-specific antigen (PSA) without documented evidence of metastatic disease have limited treatment options.
In this study, the authors sought to determine the effects of pomegranate juice consumption on PSA progression in those patients. The pomegranate (Punica granatum L., Punicaceae) fruit has been used for centuries in ancient cultures for its medicinal purposes.1 Commercial pomegranate juice shows potent antioxidant2,3 and antiatherosclerotic4 properties attributed to its high content of polyphenols, including ellagic acid in its free and bound forms and other flavonoids.
To study the possible therapeutic effects of pomegranate juice on prostate cancer, the authors conducted a 2-year, single-center, phase II, Simon two-stage clinical trial at the Clark Urologic Center, David Geffen School of Medicine at the University of California at Los Angeles. Eligible patients had a detectable PSA > 0.2 and < 5 ng/mL that was documented as raising enough pretreatment PSA time points to calculate a baseline PSA doubling time (PSADT), no hormonal therapy before entering the study, no evidence of metastatic disease, and Gleason score (test used to grade the severity of prostate cancer, based on the 5 distinct patterns that prostate tumor cells go through as they change from normal cells) ≤ 7 (lower scores indicate less dangerous tumors).
PSA is an antigen in the blood that is measured and used to track the progression of prostate cancer. Elevated PSA (usually over 4 points) usually signifies presence or growth of cancer. The time required for the PSA level to double is the indicator of the rate of growth of the cancer. In general, PSA rises slowly, matching the fact that prostate cancer is a slow-growing cancer—so slow growing, in fact, that many older men with prostate cancer will die of other causes first. When the amount of time required to double the PSA level decreases, this can indicate that the rate of disease progression is slowing; it could theoretically slow down enough to become non-threatening, or to prolong the life of the patient.
Each patient had a minimum of 3 pretreatment PSA values measured over a minimum of 6 months before entering the study. Patients were treated with 8 ounces of pomegranate juice by mouth daily (Wonderful variety, POM Wonderful 100% pomegranate juice, Los Angeles, CA; equivalent to 570 mg total polyphenol gallic acid equivalents daily) until their disease progressed. A positive response was defined as a ≥ 50% decrease in measured serum PSA levels. Progressive disease was defined as either a >100% increase in PSA (with a minimum value of 1.0 ng/mL) compared with the best response observed (nadir) or any documentation of metastatic or recurrent disease. Patients were followed in 3-month intervals for serum PSA, and blood and urine were (P<0.02) reduction in the basal oxidative state and a significant 15% reduction (P<0.02) in the resistance of their serum samples to AAPH-induced lipid peroxidation after pomegranate juice consumption. In vitro assays comparing pretreatment and posttreatment patient serum on the growth of LNCaP (prostate cancer cells) showed a 12% decrease in cell proliferation (P=0.0048) and a 17% increase in apoptosis (programmed cell death, P=0.0004), as well as significant (P<0.02) reductions in oxidative state and sensitivity to oxidation of serum lipids after vs. before pomegranate juice consumption. A 23% increase in serum nitric oxide (P = 0.0085) was also reported, which would suggest a possible vasodilating effect resulting in lowered blood pressure. No serious adverse events were reported and the treatment was well tolerated.
The authors conclude that “this study shows statistically significant effects [of pomegranate juice] on PSADT coupled with corresponding effects on prostate cancer in vitro cell growth and apoptosis,” but that the “proposed benefits shown in this study are in assays that are as yet unvalidated, and further research is needed to prove the validity of these tests and to determine whether improvements in such biomarkers (including PSADT) are likely to serve as surrogates for clinical benefit.” Their results are being further tested in a randomized, double-blind, three-arm, placebo-controlled study (begun in April 2006), in which the ability of two pomegranate juice doses to produce a predefined alternation in PSA kinetics is being compared with the change observed in a control group. If the results of that study are positive, “a strong rationale would exist for research on other plant polyphenols that might mediate similar effects,” say the authors.
—Shari Henson References
Source : American Botanical Council
Link to Source
Oral Administration of Pomegranate Seed Oil Shows Favorable Effects on Lipid Profiles of Hyperlipidemic Subjects
Mirmiran P, Fazeli MR, Asghari G, Shafiee A, Azizi F. Effect of pomegranate seed oil on hyperlipidaemic subjects: a double-blind placebo-controlled clinical trial. Br J Nutr. 2010;104:402-406.
Normalization of dyslipidemia has been shown to prevent or reduce the risk of cardiovascular disease. In order to avoid the adverse effects associated with pharmacologic therapies, research has been focusing on non-pharmacologic hypolipidemic alternatives. In vitro and in vivo studies have shown that punicic acid (PA), the conjugated fatty acid which is the main constituent of pomegranate (Punica granatum) seed oil (PSO), has anti-atherogenic effects. PSO consists of about 80% conjugated octadecatrienoic fatty acids, with a high content of 9-cis-, 11-trans-, 13-cis-acid or PA, one of the isomers of conjugated linolenic acid (CLN).1 This double-blind, placebo-controlled, randomized clinical trial was aimed at determining the effect of PSO treatment on serum lipid profiles of hyperlipidemic subjects.
Forty-five hyperlipidemic subjects aged over 20 years, with body mass index (BMI) ≤ 35 kg/m2, serum total cholesterol > 5.2 mmol/l, and serum triacylglycerol (TAG) > 1.65 mmol/l were randomly assigned to the treatment (n = 25) or the control (n = 26) groups, and received 400 mg of PSO (Pometane; Vitane Pharma Gmbh Inc; Wolfratshausen, Germany) or placebo twice daily for 4 weeks. Mean values for baseline body weight and age were 74.2 [standard deviation (SD) 10.0] and 75.7 (SD 12.2) kg, and 51 (SD 9) and 55 (SD 9) years for the PSO and placebo groups, respectively. No significant differences between the groups were seen for age, sex, weight, height, dietary intake, physical activity, and consumption of lipid lowering drugs. Serum concentrations of lipids and lipoproteins, as well as waist:hip ratio and body composition, were measured before and 4 weeks after intervention. Differences between the 2 groups at baseline were tested with Student's t test and the Mann-Whitney test. Paired Student's t test and Wilcoxon ranked test were used to compare the baseline and 4-week values in each group. Analysis of covariance was used to distinguish treatment effect between the groups following adjustment of their baseline values.
PSO administration resulted in a decrease in serum TAG concentration [2.75 mmol/l (SD 1.40) versus 3.45 mmol/l (SD 1.56); P < 0.01] and a non-significant increase in high-density lipoprotein cholesterol (HDL-C) concentration compared with baseline values; TAG:HDL-C ratio decreased significantly within the PSO group [5.73 (SD 4.55) versus 7.49 (SD 4.95); P < 0.031]. Comparison of treatment effects between the groups with baseline values as covariates revealed decreased values for cholesterol:HDL-C [5.45 (SD 1.51) versus 5.89 (SD 1.43); P < 0.05] and non-significantly higher HDL-C concentrations [1.38 mmol/l (SD 0.44) versus 1.25 mmol/l (SD 0.26); P = 0.059] in the PSO group, compared to placebo. Other lipid profile variables including cholesterol, low-density lipoprotein cholesterol (LDL-C), oxidized LDL, and LDL-C:HDL-C ratio revealed no significant differences within or between groups. A trend toward a reduced fat mass, BMI, and waist:hip ratio was noted in the PSO group. Mean differences in HDL-C concentration and cholesterol:HDL-C ratio were significant when the treatment group was compared to the placebo group (0.13 versus -0.02 mmol/l; -0.42 versus 0.01, respectively; P < 0.05).
The authors conclude that PSO consumption in hyperlipidemic subjects reduced serum TAG concentration, TAG:HDL-C and cholesterol:HDL-C ratio compared to placebo during the 4-week study period. Given the indication that each mg/dl increase in HDL-C corresponds to a 2-3% risk reduction of coronary heart disease (CHD), the decrease in serum TAG (from 3.45 to 2.75 mmol/l) and HDL-C increase of 50 mg/l observed in this study seems clinically valuable, reflecting a 10-15% risk reduction of CHD. Further studies with larger samples and longer duration are needed to confirm the effects and mechanisms of action of PSO.
p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: "Times New Roman"; }div.Section1 { page: Section1; }—p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: "Times New Roman"; }div.Section1 { page: Section1; }Silvia Giovanelli Ris
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p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: "Times New Roman"; }div.Section1 { page: Section1; }1Lansky EP, Newman RA. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol. 2007;109:177-206.
Source : American Botanical Council
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Satomi Koyama,1 Laura J Cobb,1 Hemal H Mehta,1 Navindra P. Seeram,2 David Heber,2 Allan J. Pantuck,3 and Pinchas Cohen11
Division of Pediatric Endocrinology, Mattel Children's Hospital, David Geffen School of Medicine, University of California, Los Angeles
2Center for Human Nutrition, David Geffen School of Medicine, UCLA
3 Department of Urology, David Geffen School of Medicine, UCLA
Abstract
The IGF axis is critical for the regulation of apoptosis in many human cancer cell lines. Recently, potent anti-tumorigenic effects of pomegranate juice and extracts have been reported. Consequently, pomegranate has potential not only as a treatment but also as a preventative measure against certain types of cancer, including prostate. In this study, we investigated the relationship between pomegranate-induced apoptosis in human prostate cancer cells and the IGF/IGFBP system. Treatment of LAPC4 prostate cancer cells with 10 μg/ml POMx, a highly potent pomegranate extract prepared from skin and arils minus seeds and standardized to ellagitannin content (37% punicalagins by HPLC), resulted in inhibition of cell proliferation and induction of apoptosis. Interestingly, co-treatment with POMx and IGFBP-3 revealed synergistic stimulation of apoptosis and additive inhibition of cell growth. Western blot analysis revealed that treatment with POMx or POMx/IGFBP-3 combination resulted in increased JNK phosphorylation, and decreased Akt and mTOR activation, consistent with a growth inhibitory, pro-apoptotic function. We also investigated the relationship between IGF-1 and pomegranate-induced apoptosis in 22RV1 prostate cancer cells. Co-treatment with 100 ng/ml IGF-1 completely blocked apoptosis induction by POMx. In contrast, IGF-I failed to inhibit POMx-induced apoptosis in R- cells, suggesting the importance of IGF-IR. POMx-treatment decreased Igf1 mRNA expression in a dose-dependent manner indicating that its actions also involve tumor-specific suppression of IGF-1. These studies revealed novel interactions between the IGF system and pomegranate-induced apoptosis.
In conclusion, these studies reveal novel interactions between the IGF system and pomegranate-induced apoptosis, and suggest that pomegranate products modulate the tumor production and responsiveness to IGFs and the IGFBPs. As IGFBP-3 is currently being tested in humans as a treatment for prostate cancer and pomegranate supplements are becoming popular as adjuvant nutritional treatments for this disease, we propose that these agents may emerge as useful in the management of prostate cancer.
Source : Growth Horm IGF Res. 2010 February; 20(1): 55.
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Pomegranate extract inhibits androgen-independent prostate cancer growth through a nuclear factor-κB-dependent mechanism
Matthew B. Rettig 25,David Heber4, Jiabin An5,Navindra P. Seeram4,Jian Y. Rao3, Huiren Liu1,Tobias Klatte2,Arie Belldegrun2,Aune Moro4,Susanne M. Henning4, Deqiong Mo5,William J. Aronson26 and Allan Pantuck2
Abstract
Constitutive nuclear factor-κB (NF-κB) activation is observed in androgen-independent prostate cancer and represents a predictor for biochemical recurrence after radical prostatectomy. Dietary agents such as pomegranate extract (PE) have received increasing attention as potential agents to prevent the onset or progression of many malignancies, including prostate cancer. Here, we show that PE inhibited NF-κB and cell viability of prostate cancer cell lines in a dose-dependent fashion in vitro. Importantly, maximal PE-induced apoptosis was dependent on PE-mediated NF-κB blockade. In the LAPC4 xenograft model, PE delayed the emergence of LAPC4 androgen-independent xenografts in castrated mice through an inhibition of proliferation and induction of apoptosis. Moreover, the observed increase in NF-κB activity during the transition from androgen dependence to androgen independence in the LAPC4 xenograft model was abrogated by PE. Our study represents the first description of PE as a promising dietary agent for the prevention of the emergence of androgen independence that is driven in part by heightened NF-κB activity.
.....Extending the duration of the androgen-dependent state could potentially prolong life expectancy of prostate cancer patients and delay or prevent the need for additional hormonal therapy or chemotherapy. In this regard, our finding that PE delayed the growth and emergence of androgen independence in our xenograft model may be particularly germane. Of importance, our group showed previously that dietary fat reduction delayed the emergence of androgen independence and prolonged survival using a similar xenograft model (36). Future research will focus on potential additive and/or synergistic effects of combining a low-fat diet with PE. Based on our results, we propose that PJ could have potential as a dietary agent to prevent the emergence of androgen independence and suggest that this may be a high priority area for future clinical investigation.
Source : Mol Cancer Ther 2008;7(9):2662–71
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Potential Therapeutic Effects of Pomegranate Juice on Prostate Cancer
Reviewed: Pantuck AJ, Leppert JT, Zomorodian N, et al. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin Cancer Res. 2006;12(13):4018-4026.
Although the 5-year survival rate for men with prostate cancer has increased dramatically, from a 67% survival rate in the 1970s to over 90% in recent years when caught and treated early, prostate cancer is still the most common cancer (excluding skin cancer) and the second leading cause of cancer-related death in men in the United States.
Primary management of the disease for most men is either radical surgery or radiation therapy. In a significant number of men, the disease metastasizes. According to the authors, patients who have undergone primary management to cure the disease and who have progressive elevation of their prostate-specific antigen (PSA) without documented evidence of metastatic disease have limited treatment options.
In this study, the authors sought to determine the effects of pomegranate juice consumption on PSA progression in those patients. The pomegranate (Punica granatum L., Punicaceae) fruit has been used for centuries in ancient cultures for its medicinal purposes.1 Commercial pomegranate juice shows potent antioxidant2,3 and antiatherosclerotic4 properties attributed to its high content of polyphenols, including ellagic acid in its free and bound forms and other flavonoids.
To study the possible therapeutic effects of pomegranate juice on prostate cancer, the authors conducted a 2-year, single-center, phase II, Simon two-stage clinical trial at the Clark Urologic Center, David Geffen School of Medicine at the University of California at Los Angeles. Eligible patients had a detectable PSA > 0.2 and < 5 ng/mL that was documented as raising enough pretreatment PSA time points to calculate a baseline PSA doubling time (PSADT), no hormonal therapy before entering the study, no evidence of metastatic disease, and Gleason score (test used to grade the severity of prostate cancer, based on the 5 distinct patterns that prostate tumor cells go through as they change from normal cells) ≤ 7 (lower scores indicate less dangerous tumors).
PSA is an antigen in the blood that is measured and used to track the progression of prostate cancer. Elevated PSA (usually over 4 points) usually signifies presence or growth of cancer. The time required for the PSA level to double is the indicator of the rate of growth of the cancer. In general, PSA rises slowly, matching the fact that prostate cancer is a slow-growing cancer—so slow growing, in fact, that many older men with prostate cancer will die of other causes first. When the amount of time required to double the PSA level decreases, this can indicate that the rate of disease progression is slowing; it could theoretically slow down enough to become non-threatening, or to prolong the life of the patient.
Each patient had a minimum of 3 pretreatment PSA values measured over a minimum of 6 months before entering the study. Patients were treated with 8 ounces of pomegranate juice by mouth daily (Wonderful variety, POM Wonderful 100% pomegranate juice, Los Angeles, CA; equivalent to 570 mg total polyphenol gallic acid equivalents daily) until their disease progressed. A positive response was defined as a ≥ 50% decrease in measured serum PSA levels. Progressive disease was defined as either a >100% increase in PSA (with a minimum value of 1.0 ng/mL) compared with the best response observed (nadir) or any documentation of metastatic or recurrent disease. Patients were followed in 3-month intervals for serum PSA, and blood and urine were (P<0.02) reduction in the basal oxidative state and a significant 15% reduction (P<0.02) in the resistance of their serum samples to AAPH-induced lipid peroxidation after pomegranate juice consumption. In vitro assays comparing pretreatment and posttreatment patient serum on the growth of LNCaP (prostate cancer cells) showed a 12% decrease in cell proliferation (P=0.0048) and a 17% increase in apoptosis (programmed cell death, P=0.0004), as well as significant (P<0.02) reductions in oxidative state and sensitivity to oxidation of serum lipids after vs. before pomegranate juice consumption. A 23% increase in serum nitric oxide (P = 0.0085) was also reported, which would suggest a possible vasodilating effect resulting in lowered blood pressure. No serious adverse events were reported and the treatment was well tolerated.
The authors conclude that “this study shows statistically significant effects [of pomegranate juice] on PSADT coupled with corresponding effects on prostate cancer in vitro cell growth and apoptosis,” but that the “proposed benefits shown in this study are in assays that are as yet unvalidated, and further research is needed to prove the validity of these tests and to determine whether improvements in such biomarkers (including PSADT) are likely to serve as surrogates for clinical benefit.” Their results are being further tested in a randomized, double-blind, three-arm, placebo-controlled study (begun in April 2006), in which the ability of two pomegranate juice doses to produce a predefined alternation in PSA kinetics is being compared with the change observed in a control group. If the results of that study are positive, “a strong rationale would exist for research on other plant polyphenols that might mediate similar effects,” say the authors.
—Shari Henson References
- Longtin R. The pomegranate: nature’s power fruit? J Natl Cancer Inst. 2003;95:346-348.
- Gil MI, Tomas-Barberan FA, Hess-Pierce B, Holcroft DM, Kader AA. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem. 2001;48:4581-4589.
- Fuhrman B, Aviram M. Flavonoids protect LDL from oxidation and attenuate atherosclerosis. Curr Opin Lipidol. 2001;12:41-48.
- Aviram M, Rosenbalt M, Gaitini D, et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr. 2004;23:423-433.
Source : American Botanical Council
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Oral Administration of Pomegranate Seed Oil Shows Favorable Effects on Lipid Profiles of Hyperlipidemic Subjects
Mirmiran P, Fazeli MR, Asghari G, Shafiee A, Azizi F. Effect of pomegranate seed oil on hyperlipidaemic subjects: a double-blind placebo-controlled clinical trial. Br J Nutr. 2010;104:402-406.
Normalization of dyslipidemia has been shown to prevent or reduce the risk of cardiovascular disease. In order to avoid the adverse effects associated with pharmacologic therapies, research has been focusing on non-pharmacologic hypolipidemic alternatives. In vitro and in vivo studies have shown that punicic acid (PA), the conjugated fatty acid which is the main constituent of pomegranate (Punica granatum) seed oil (PSO), has anti-atherogenic effects. PSO consists of about 80% conjugated octadecatrienoic fatty acids, with a high content of 9-cis-, 11-trans-, 13-cis-acid or PA, one of the isomers of conjugated linolenic acid (CLN).1 This double-blind, placebo-controlled, randomized clinical trial was aimed at determining the effect of PSO treatment on serum lipid profiles of hyperlipidemic subjects.
Forty-five hyperlipidemic subjects aged over 20 years, with body mass index (BMI) ≤ 35 kg/m2, serum total cholesterol > 5.2 mmol/l, and serum triacylglycerol (TAG) > 1.65 mmol/l were randomly assigned to the treatment (n = 25) or the control (n = 26) groups, and received 400 mg of PSO (Pometane; Vitane Pharma Gmbh Inc; Wolfratshausen, Germany) or placebo twice daily for 4 weeks. Mean values for baseline body weight and age were 74.2 [standard deviation (SD) 10.0] and 75.7 (SD 12.2) kg, and 51 (SD 9) and 55 (SD 9) years for the PSO and placebo groups, respectively. No significant differences between the groups were seen for age, sex, weight, height, dietary intake, physical activity, and consumption of lipid lowering drugs. Serum concentrations of lipids and lipoproteins, as well as waist:hip ratio and body composition, were measured before and 4 weeks after intervention. Differences between the 2 groups at baseline were tested with Student's t test and the Mann-Whitney test. Paired Student's t test and Wilcoxon ranked test were used to compare the baseline and 4-week values in each group. Analysis of covariance was used to distinguish treatment effect between the groups following adjustment of their baseline values.
PSO administration resulted in a decrease in serum TAG concentration [2.75 mmol/l (SD 1.40) versus 3.45 mmol/l (SD 1.56); P < 0.01] and a non-significant increase in high-density lipoprotein cholesterol (HDL-C) concentration compared with baseline values; TAG:HDL-C ratio decreased significantly within the PSO group [5.73 (SD 4.55) versus 7.49 (SD 4.95); P < 0.031]. Comparison of treatment effects between the groups with baseline values as covariates revealed decreased values for cholesterol:HDL-C [5.45 (SD 1.51) versus 5.89 (SD 1.43); P < 0.05] and non-significantly higher HDL-C concentrations [1.38 mmol/l (SD 0.44) versus 1.25 mmol/l (SD 0.26); P = 0.059] in the PSO group, compared to placebo. Other lipid profile variables including cholesterol, low-density lipoprotein cholesterol (LDL-C), oxidized LDL, and LDL-C:HDL-C ratio revealed no significant differences within or between groups. A trend toward a reduced fat mass, BMI, and waist:hip ratio was noted in the PSO group. Mean differences in HDL-C concentration and cholesterol:HDL-C ratio were significant when the treatment group was compared to the placebo group (0.13 versus -0.02 mmol/l; -0.42 versus 0.01, respectively; P < 0.05).
The authors conclude that PSO consumption in hyperlipidemic subjects reduced serum TAG concentration, TAG:HDL-C and cholesterol:HDL-C ratio compared to placebo during the 4-week study period. Given the indication that each mg/dl increase in HDL-C corresponds to a 2-3% risk reduction of coronary heart disease (CHD), the decrease in serum TAG (from 3.45 to 2.75 mmol/l) and HDL-C increase of 50 mg/l observed in this study seems clinically valuable, reflecting a 10-15% risk reduction of CHD. Further studies with larger samples and longer duration are needed to confirm the effects and mechanisms of action of PSO.
p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: "Times New Roman"; }div.Section1 { page: Section1; }—p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: "Times New Roman"; }div.Section1 { page: Section1; }Silvia Giovanelli Ris
p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: "Times New Roman"; }div.Section1 { page: Section1; }Reference
p.MsoNormal, li.MsoNormal, div.MsoNormal { margin: 0in 0in 0.0001pt; font-size: 12pt; font-family: "Times New Roman"; }div.Section1 { page: Section1; }1Lansky EP, Newman RA. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol. 2007;109:177-206.
Source : American Botanical Council
Link to Source