Pomegranate (Punica granatum), was one of the earliest fruits from warmer parts of the world to become popular in Europe. Native to the Middle East, traditional uses include for the treatment of dysentery and diarrhoea. It now seems that the more scientists look, the more they are finding about this famous fruit.  Research findings published over the past year alone, have implications for the management of conditions such as bowel disease, skin conditions, cancer and pain.

Multiple therapeutically active polyphenols are found in the fruits of pomegranate, including anthocyanins and anthocyanidins, flavones, flavonoids and flavonols. The rind or peels, often discarded when juice products are prepared, are also rich in useful phytochemicals and have a high content of hydrolysable ellagitannins such as punicalagin, ellagic acid and punicic acid.

Anticancer properties

Dietary factors are increasingly linked with the risks of certain cancers^(1,2,3). While the incidence of prostate cancer in Asian countries is low compared to the West, this incidence increases by as much as 20-fold in Asian immigrants to the United States. Their adoption of a Western diet, a reduced intake of soy, tea, fish, fruits, and vegetables and increased intake of red meat and fat-rich foods, are thought to be largely contributory^{(4, 5]}. 

Many foods rich in polyphenols have been associated with cancer prevention, effects attributable largely to their antioxidant and free radical scavenging properties.  Pomegranate is one of these, and anti-cancer effects have been measured in vitro for pomegranate fruit extracts using a wide range of different cancer cell lines, including ovarian⁽⁶⁾, bladder⁽⁷⁾, thyroid⁽⁸⁾,  breast⁽⁹⁾ and prostate cancer, and multiple myeloma⁽¹⁰⁾.

Flavonoid-rich polyphenol fractions have been reported to exert anti-proliferative, anti-invasive, anti-inflammatory and other anti-cancer actions in breast and prostate cancer cells in vitro and in animal studies⁽¹¹⁾.  Pomegranate extracts also inhibit the formation of new blood vessels (angiogenesis) by cancer cells⁽¹²⁾, and have been shown to have potential to help suppress the final steps of carcinogenesis and metastasis^{(2, 13, 14)}.

The state of the gut community of microbes is increasingly linked with a large number of chronic health conditions, and there is growing evidence of an influence of the gut microbiota on mechanisms of prostate cancer initiation and/or progression⁽¹⁵⁾. Changes to the gut microbiome through changes in dietary composition and increased intake of vegetables and polyphenols, may help to modify the risk of prostate cancer through its role in the regulation of chronic inflammation, apoptotic (cell death) processes, cytokines, and hormonal production⁽¹⁵⁾.

Ellagitannins are bioactive polyphenols and a principle component of pomegranate peels and other foods such as seeds, nuts and berries with chemopreventive potential against prostate and other cancers. Too large to be absorbed into the bloodstream intact, they are partially hydrolyzed in the gut to ellagic acid. Ellagic acid and its metabolite urolithin A, produced by colonic microflora, have demonstrated significant antioxidant and anticancer effects, including antiproliferative and apoptotic activities^{(16, 17)}, and inhibition of angiogenesis^{(18, 19)}, in a range of cancer types. 

At least 6 clinical trials involving prostate cancer patients have been undertaken, and while these suggest daily ingestion of sufficiently large doses of pomegranate extracts can produce a significant slowing of PSA increase ^(20-23), further trials with larger patient numbers and longer treatment durations, are required.

A recent review also supports potential applications to help protect against breast cancer⁽⁹⁾. This is supported by a significant number of studies including reports that pomegranate extracts induce cell cycle arrest in the G0/G1 phase, and induce cytotoxicity in a dose- and time-dependent manner.  Inhibitory effects of pomegranate juice on bladder cancer development, have also been reported recently in rats⁽⁷⁾. Correction of the expression of pro-inflammatory cytokines and suppression of angiogenesis, were associated with these benefits.

Gastroprotective properties

The traditional uses of pomegranate rinds for the treatment of dysentery and diarrhea, is a reflection of both their tannin content and proven antimicrobial activities, but also suggests potential gastrointestinal protective and anti-inflammatory properties.

Ellagitannins seem to contribute to most of the beneficial analgesic and anti-inflammatory actions of pomegranate in a rat model of inflammatory bowel disease⁽²⁴⁾. Again, their metabolites ellagic acid and urolithin A, formed by the gut microbiotica following pomegranate consumption, seem to be involved. Urolithin A is increasingly linked not only to protecting against bowel and other cancers, but to having beneficial anti-inflammatory actions of possible relevance to inflammatory bowel conditions such as ulcerative colitis and Crohn’s disease, and other gastrointestinal conditions⁽²⁵⁾. Protective effects against gastric ulcers have been recently reported in animal studies⁽²⁶⁾. Anthelminthic activity, thus helping to expel parasitic worms from the gut, is another recently documented application shown against nematodes in sheep⁽²⁷⁾.

Skin health:

In vitro and animal studies have demonstrated that topical application and oral consumption of pomegranate reduces UVB-induced skin damage from the sun⁽²⁸⁾. Oral feeding of pomegranate fruit extract to mice protected them from the adverse effects of UVB radiation, by interfering with early stages of photocarcinogenesis⁽²⁹⁾.

A double-blind, placebo-controlled trial involving female subjects age 20–40s found daily ingestion of an ellagic acid-rich pomegranate extract had an inhibitory effect on skin pigmentation caused by UV irradiation⁽³⁰⁾. Another trial found protection against UVB irradiation following oral ingestion of pomegranate juice or pomegranate extract, in a group of healthy females aged 30-45 years⁽²⁸⁾. Influences on the gut or skin microbiome, have again been implicated in these photoprotective effects.

Eczema or dermatitis is a frequent side effect of chemotherapy and radiotherapy treatment in cancer patients, and recent research found pomegranate to promote skin regeneration processes after skin damage induced by 5-fluorouracil⁽³¹⁾. This suggests a potential use of pomegranate as an adjuvant during treatment with this and perhaps other chemotherapy drugs. Welsh dental researchers have also recently reported that the peel ellagitannin punicalagin in combination with zinc, may promote anti-inflammatory and fibroblast responses to aid healing of oral cavity wounds⁽³²⁾.

Neuroprotective effects?

Potential neuroprotective effects have been recently reported in animal models of Parkinsons disease^{(33, 34)}. A pilot clinical trial also found pomegranate to protect against memory impairment and improve memory retention performance for up to 6 weeks after cardiac surgery⁽³⁵⁾. As with cancer protective and gastroprotective activities, urolithin A has been implicated in these neuroprotective activities^{(25, 36)}.

Preliminary clinical trials recently conducted at Harvard Medical School, have also found supplementation with pomegranate juice by pregnant women may help to protect their fetuses against intrauterine growth restriction, a serious complication with a risk of perinatal death or neurodevelopmental impairment among surviving infants^{(37, 38)}.  A pomegranate seed extract has also been reported to protect against tramadol-induced testicular toxicity in animal studies⁽³⁹⁾. Usage of this painkilling drug is now very common in hospital and community settings around the world, and taking adjunctive pomegranate may help protect against its negative effects on male fertility, particularly during adolescence.

References:

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