Wilt thou be gone? It is not yet near day. It was the nightingale, and not the lark, That pierced the fearful hollow of thine ear. Nightly she sings on yon pomegranate-tree. Believe me, love, it was the nightingale.
Romeo and Juliet, III, 5
The pomegranate is an ancient fruit that has not changed much throughout the history of man. After the discovery of agriculture about 10,000 years ago, we know that it was grown in Egypt. It was found in the Indus Valley so early that there is a word in Sanskrit for pomegranate. Indian royalty began their banquets with pomegranate, grape, and jujube.
The pomegranate is also significant in Jewish tradition. The pomegranate is said to have 613 seeds to represent the 613 commandments in the Torah. While this has not been confirmed in modern times, the image of the pomegranate was woven into the high priest's robes, and brass representations were part of the ancient Temple's pillars. The pomegranate is mentioned six times in the Song of Solomon, and even today silver-plated representations of pomegranates are used to cover the wooden handles of the Torah scrolls.
The pomegranate appeared in China during the Han and Sung dynasties, probably brought from the Middle East by traders. It was slowly adopted in medieval Europe but was known in Elizabethan England, as can be seen by the quote above from Romeo and Juliet. The Spanish conquistadores brought the pomegranate to America. Jesuit missionaries carried it north to California, where it now grows in abundance in that state's mild Mediterranean-like climate.
The biochemistry of the pomegranate is fascinating, and its several very different classes of compounds are discussed in detail in this book. The red/purple color of anthocyanins provides the rich color of the skin. Anthocyanins are also found in the arils (the botanical term for the part commonly consumed, including the flesh and the seed) along with traces of an astringent family of compounds known as the hydrolyzable tannins. Among these, pomegranate juice made by squeezing the whole fruit is a rich source of a large polyphenol antioxidant — an ellagitannin known as punicalagin. This molecule with a molecular weight of over 1000 Daltons does not enter the human body intact. Instead, it is broken up into ellagic acid moieties released into the bloodstream over several hours. It is also metabolized by colonic bacteria to urolithins and their conjugates, which appear in the blood and urine. The family of phytochemicals found in pomegranate juice extracts, made by squeezing the whole fruit, act together with greater potency than any of the single constituents alone, as is the case with many different fruits, vegetables, and herbs. The seeds also contain a rare lipid called punicic acid that is similar to conjugated linoleic acid but has an additional double bond.
The physiological effects of pomegranate juice constituents are remarkable in their preventive potential against two of the major chronic diseases of aging — heart disease and cancer.
First, in heart disease, the pioneering work of Michael Aviram on pomegranate polyphenols has demonstrated their ability to reduce lipid peroxidation and the progression of atherosclerosis in animal models. One clinical study demonstrated improved cardiac muscle perfusion in a group of patients with heart disease. Nobel Prize winner Lou Ignarro demonstrated marked enhancement of nitric oxide production in endothelial cells, which reveals another exciting and perhaps primary mode for the prevention of cardiovascular disease.
Second, there are significant new findings suggesting that pomegranate juice may be active against common forms of cancer. In basic laboratory studies, pomegranate juice extracts and the tannins as well as anthocyanins have significant antiproliferative and proapoptotic effects in several different types of cancer cells in vitro including colon cancer, prostate cancer, and head and neck cancer. In colon cancer cell lines that express cyclo-oxygenase 2 enzyme, we have demonstrated together with Bharat Aggarwal the inhibition of proliferation and Nuclear Factor kappa-B activation by pomegranate ellagitannins. In prostate cancer xenografts, pomegranate juice has been shown by Hasan Mukhtar and coworkers to reduce tumor growth. Finally, in a preliminary study of men with advanced prostate cancer and rising PSA levels performed at UCLA by Allan Pantuck, pomegranate juice reduced the rate of rise of PSA by 50% over a 1-year period. Ongoing basic and clinical research is being pursued by a number of research groups to examine the potential preventive effects of pomegranates in common forms of cancer.
Pomegranate seeds in many traditions have led to the idea that pomegranates promote fertility, but there is no evidence to that effect as yet. However, what is known of its potential phytoestrogenic effects is reviewed in some detail.
Unlocking the secrets hidden within this ancient fruit will require the application of all of our modern methods of nutritional science including nutrigenomics, proteo-mics, and detailed studies of subcellular signaling pathways in normal and diseased cells.
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