Exotic Superfruits: Literature Update

This article provides a brief look at the research directions each of the six exotic superfruits is taking. Selected from Autumn 2006 to September 2007, three articles for each fruit are presented with a synopsis; original abstracts can be viewed by visiting http://pubmed.gov and entering key words from the articles below in the search statement.

Açaí (Euterpe oleracea Mart.): A newcomer to the medical research literature, with just 11 papers published since the first appeared in 2004. PubMed search statement: “acai”.

1. Schauss AG, Wu X, Prior RL, Ou B, Patel D, Huang D, Kababick JP. “Phytochemical and nutrient composition of the freeze-dried amazonian palm berry, Euterpe oleraceae mart. (açaí).” J Agric Food Chem. 2006 Nov 1;54(22):8598-603. Synopsis: Due to the characteristic exceptional fat content of açaí pulp potentially leading to rancidity, these authors prepared freeze-dried pulp and berry skin for nutrient and phytochemical analyses. As the commercial açaí supply derives from tropical countries (in this example, Brazil), freeze-drying is a practical method for preserving the post-harvest nutrient and phytochemical value of the fruit. The authors described a rich and diverse nutrient content of high lipid (oleic and palmitic acids) and dietary fiber of the skin-pulp material, as summarized in Part 1 of this essay and reference (4). Cyanidin-3-rutinoside and cyanidin-3-glucoside were the two main anthocyanins present together with a high content of proanthocyanidin polymers. Interestingly, these phenolics were determined to be a small fraction of the total, indicating that the main antioxidant strength of açaí resides in phytochemicals as yet unidentified.

2. Schauss AG, Wu X, Prior RL, Ou B, Huang D, Owens J, Agarwal A, Jensen GS, Hart AN, Shanbrom E. “Antioxidant capacity and other bioactivities of the freeze-dried Amazonian palm berry, Euterpe oleraceae mart. (açaí).” J Agric Food Chem. 2006 Nov 1;54(22):8604-10. Synopsis: In a companion study to the one above, the authors demonstrated an exceptionally high scavenging ability of açaí phenolic extracts in vitro against the superoxide anion, the most common oxygen radical in mammals. These results yielded the highest total oxygen radical absorbance capacity (ORAC) yet measured in a plant food, 1027 units per gram. An in vitro assay measuring inhibition of reactive oxygen species formation in human neutrophils showed that antioxidants in açaí were able to enter human cells and serve an oxygen quenching function at low doses. Furthermore, açaí was found to inhibit cyclo-oxygenase (COX)-1 and COX-2 enzymes involved in inflammatory and immune functions, indicating a possible mechanism for health benefits of this berry to be defined in future research.

3. Neida S, Elba S. “[Characterization of the açaí or manaca (Euterpe oleracea Mart.): a fruit of the Amazon].” Arch Latinoam Nutr. 2007 Mar;57(1):94-8. [Article in Spanish] Synopsis: In this constituent analysis of açaí pulp (“manaca”) from the Venezuelan Amazon, the authors confirmed the results of Schauus et al. above, showing an exceptional high lipids content (33% total mass), protein (average 11%), and total dietary fiber (average 22%). 71% of açaí lipids were oleic acid. Polyphenols, tannins and anthocyanins were found in high density, giving the pulp the extraordinary antioxidant capacity demonstrated by the Schauss study. Venezuelan açaí has a high nutritional value and contains abundant antioxidant compounds.

In summary for açaí, studies 1 and 3 confirm the commercial challenge for harvesting, processing and storing açaí raw materials. The fruit's high fat content and susceptibility to rancidity dictate that it likely cannot be processed or shipped from the tropics fresh or as a juice. This restriction limits its applications, since freeze-dried powders containing high amounts of fiber and residual fats are perhaps the most convenient form of raw material, but will be a solubility challenge for beverage applications. A potential benefit of freeze-drying, however, is preservation of exceptional content of antioxidant phenolics in açaí, allowing definition of the highest ORAC value yet recorded in a plant food (spices excepted). Despite these limitations, development of new SKUs for açaí is occurring at a rapid rate, promising significant growth in consumer popularity.

Goji (Wolfberry) (Lycium barbarum L.): Searching for “lycium barbarum”, “lycium chinense” or “wolfberry” on the PubMed finds 148 publications since the first report in 1963. Having not been used in scientific literature, the name “goji” retrieves no results in a PubMed search.

1. Ho YS, Yu MS, Lai CS, So KF, Yuen WH, Chang RC. “Characterizing the neuroprotective effects of alkaline extract of Lycium barbarum on beta-amyloid peptide neurotoxicity.” Brain Res. 2007 Jul 16;1158:123-34. Synopsis: These authors extracted glycoconjugate fractions from goji berries then tested them in vitro against the activity of caspase-3 enzymes, a marker of amyloid toxicity in isolated cortical neurons. The goji fractions inhibited caspase and lactate dehydrogenase activities, providing evidence that goji extracts could block apoptotic (rate of natural cell death) mechanisms in this in vitro model of brain function. The results are evidence for a potential mechanism by which consumption of goji could deter neurodegeneration, but such a conclusion requires extensive further basic and clinical research to demonstrate this effect.

2. Xin YF, Zhou GL, Deng ZY, Chen YX, Wu YG, Xu PS, Xuan YX. “Protective effect of Lycium barbarum on doxorubicin-induced cardiotoxicity.” Phytother Res. 2007 Jul 11; [Epub ahead of print] Synopsis: The objective of this work in rats was to test the hypothesis that Lycium barbarum protects against doxorubicin-induced toxicity of the heart through antioxidant-mediated mechanisms. Where control doxorubicin-treated animals showed signs of cardiac injury and higher mortality, those provided orally with 25 mg/kg/day of goji extract over 3 weeks had less myocardial fibril injury and improved overall heart function. The results indicate possible antioxidant effects of goji constituents against cardiotoxicity.

3. Chan HC, Chang RC, Koon-Ching Ip A, Chiu K, Yuen WH, Zee SY, So KF. “Neuroprotective effects of Lycium barbarum Lynn on protecting retinal ganglion cells in an ocular hypertension model of glaucoma.” Exp Neurol. 2007 Jan;203(1):269-73. Synopsis: One of the most enduring Chinese legends of eating goji berries is for its eye health benefit. This research team tested whether goji could promote the survival of retinal ganglion cells against elevated intraocular pressure (a model of glaucoma) induced experimentally in rats. Oral administration of goji significantly reduced the loss of retinal ganglion cells in the model, providing evidence for protection against retinal cell degeneration during high intraocular pressure seen in glaucoma.

In summary, although a rich history of its medicinal applications exists in Chinese legend, goji has neither yet been shown in basic medical research nor in human studies to have any conclusive pharmacological properties. These three studies demonstrated protective effects by goji extracts on brain, heart and ocular functions, although the models and results are preliminary to more complete biological definition and human clinical trials.

Mangosteen (Garcinia mangostana L.): Medical research interest in mangosteen (also search PubMed for “mangostin” or “mangostana”) began in 1940 now with a total of just 53 papers including only 8 in the last year.

1. Fu C, Loo AE, Chia FP, Huang D. “Oligomeric proanthocyanidins from mangosteen pericarps.” J Agric Food Chem. 2007 Sep 19;55(19):7689-94. Synopsis: Although the inedible exocarp (rind) of mangosteen is known primarily for its content of xanthone antioxidants, this study demonstrated the presence of other phenolic pigments, such as proanthocyanidins, prodelphinidin, gallic acid, catechins and their oligomers. These phenolics are not expected to exist in the white fruit pulp. By inference, mangosteen juices made from purées of fruit pulp and exocarp contain a mixture of xanthones and these other phenolics. The results are important for applying exocarp extractions in mangosteen juice blends because the presence of phenolics other than xanthones diversify and strengthen the antioxidant value of such juices.

2. Walker EB. “HPLC analysis of selected xanthones in mangosteen fruit.” J Sep Sci. 2007 Jun;30(9):1229-34. Synopsis: This study explored extraction methods using high-performance liquid chromatography for optimizing recovery of xanthones from the mangosteen exocarp. Several newly discovered xanthones are listed and numbered here (total of 28 isolated to date) as a preliminary catalog (not intended to be comprehensive): 1) alpha-mangostin, 2) 8-desoxygartanin, 3) gartanin, 4) beta-mangostin, 5) 3-mangostin, and 6) 9-hydroxycalabaxanthone. Xanthones isolated in previous studies include 7) 8-hydroxycudraxanthone G, 8) mangostingone [7-methoxy-2-(3-methyl-2-butenyl)-8-(3-methyl-2-oxo-3-butenyl)-1,3,6-trihydroxyxanthone, 2], 9) cudraxanthone G, 10-12) garcimangosones A-C, 13) garcinone D, 14) garcinone E, 15) 1-isomangostin, 16) gamma-mangostin, 17) mangostinone, 18) smeathxanthone A, 19) tovophyllin A, 20) mangoxanthone, 21) dulxanthone D, 22) [1,3,7-trihydroxy-2-methoxyxanthone, 1,3,5-trihydroxy-13,13-dimethyl-2H-pyran[7,6-b]xanthen-9-one], 23) mangosharin, (2,6-dihydroxy-8-methoxy-5-(3-methylbut-2-enyl)-xanthone), 24) 1,6-dihydroxy-3,7-dimethoxy-2-(3-methylbut-2-enyl)-xanthone, 25) mangostanol, 26) 5,9-dihydroxy-8- methoxy-2,2-dimethyl-7-(3-methylbut-2-enyl)-2H,6H-pyrano-[3,2-b]-xanthene-6-one, and 27-28) afzeliixanthones A and B. Thus, a total of 28 individual xanthones have been isolated to date from mangosteen.

3. Nakagawa Y, Iinuma M, Naoe T, Nozawa Y, Akao Y. “Characterized mechanism of alpha-mangostin-induced cell death: caspase-independent apoptosis with release of endonuclease-G from mitochondria and increased miR-143 expression in human colorectal cancer DLD-1 cells.” Bioorg Med Chem. 2007 Aug 15;15(16):5620-8. Synopsis: In this study of human colonic cancer cells in vitro, the mangosteen xanthone, alpha-mangostin, was shown to stimulate tumor cell apoptosis (rate of natural cell death) and therefore could provide a potential anti-cancer therapy. However, considerably more development and proof for efficacy and safety in human patients are needed. When combined with the established chemopreventive agent, fluorouracil (5-FU), alpha-mangostin augmented the anti-cancer effect, indicating a potential role for both agents as a tandem therapy if eventually proved with efficacy in animal and human studies.

Undeveloped as a subject in medical research, mangosteen and its phenolic constituents are just at the threshold of establishing potential anti-disease effects. Existing research reflects the exploratory approach of laboratory studies to date – isolating and characterizing the chemistry and preliminary biological activities of xanthones. There have been only five preliminary research reports identifying mangosteen xanthones with anti-cancer activity. In conclusion, at this stage of research, comments about the anti-cancer properties of mangosteen xanthones are not warranted.

Noni (Morinda citrifolia L.): Since the first report on noni in 1954, there have been 114 medical research publications including 27 in the past year. PubMed search: “noni” or “morinda citrifolia”.

1. Potterat O, Felten RV, Dalsgaard PW, Hamburger M. “Identification of TLC markers and quantification by HPLC-MS of various constituents in noni fruit powder and commercial noni-derived products.” J Agric Food Chem. 2007 Sep 5;55(18):7489-94. Synopsis: Noni iridoid glucosides, scopoletin, rutin, fatty acid glucosides, and anthraquinones were detected in several commercial noni powder and juice products. Asperulosidic acid and deacetylasperulosidic acid (both anthraquinones) and rutin (an antioxidant flavonoid) were present in all samples analyzed, but their concentrations differed considerably between products. Fatty acid glucosides, and noniosides B and C were present in capsule powders and most juices. Scopoletin was mainly found in juices. The study indicates an important trend for noni research – isolation and description of functional properties for noni phytochemicals – but reveals that noni research remains at a level indicating only preliminary understanding of the potential health properties of this fruit’s phytochemicals.

2. Deng S, West BJ, Palu AK, Zhou BN, Jensen CJ. “Noni as an anxiolytic and sedative: a mechanism involving its gamma-aminobutyric acidergic effects.” Phytomedicine. 2007 Aug;14(7-8):517-22. Synopsis: In marketing literature on noni products, a claim is often made that consumption of noni induces a calming effect on its user. Accordingly, the aim of this study conducted by a research team affiliated with the manufacturer of a major noni juice blend—Tahitian Noni International Inc.—was to investigate the effects of noni fruit on anxiety mechanisms in vitro. The investigators showed that an extract of noni had affinity for gamma-aminobutyric acid A (GABAa) inhibitory neurotransmitter receptors and displayed a high degree of competitive inhibition (showing avidity for this receptor). The authors interpret their results demonstrate binding by noni extracts to neuronal GABAa receptors and so may induce sedative effects. Such conclusions, however, are preliminary requiring further evidence for specificity and efficacy at these receptors.

3. Akihisa T, Matsumoto K, Tokuda H, Yasukawa K, Seino K, Nakamoto K, Kuninaga H, Suzuki T, Kimura Y. “Anti-inflammatory and potential cancer chemopreventive constituents of the fruits of Morinda citrifolia (Noni).” J Nat Prod. 2007 May;70(5):754-7. Synopsis: Four saccharide fatty acid esters isolated from noni fruit exhibited potent anti-inflammatory activity in situ in a mouse model. As inflammatory mechanisms are thought to be involved at the onset of cancer, these results were interpreted by the authors to represent potential anti-cancer evidence for the noni isolates. A noni anthraquinone and two newly identified saccharide fatty acid esters also had inhibitory activity against inflammation in mice. The findings provide a basis for further animal testing and identification of cellular mechanism for anti-inflammatory activity of these constituents from noni fruit.

For noni, despite more than 50 years of interest by Western scientists in its biomedical properties, the research base for this fruit remains immature with generally poor development or understanding around any noni phytochemical. No specific constituent stands out as an emerging candidate for development of a mechanism of action or therapeutic strategy, in contrast to better studied plants such as those with rich phenolic or carotenoid contents having potential health properties.

Pomegranate (Punica granatum L.): A PubMed search on pomegranate retrieved 226 reports in the medical literature since 1950 with 52 in the last year.

1. West T, Atzeva M, Holtzman DM. “Pomegranate polyphenols and resveratrol protect the neonatal brain against hypoxic-ischemic injury.” Dev Neurosci. 2007;29(4-5):363-72. Synopsis: In previous studies, these investigators showed that pomegranate juice provided protection of neonatal mouse brain against hypoxic-ischemic injury when given to mothers in their drinking water. This study tested the hypothesis that the protection was due to phenolics in the juice, and compared the results to those for resveratrol, another phenolic common in red grapes. The neuroprotective effects of resveratrol had been demonstrated in adult models of stroke, but had not previously been examined in neonates. The study showed that pomegranate phenolics and resveratrol reduced activity of the enzyme, caspase-3, following neonatal hypoxic-ischemic injury. The results indicate a protective effect of pomegranate juice in this laboratory model of ischemic oxidative stress of the newborn.

2. Seeram NP, Aronson WJ, Zhang Y, Henning SM, Moro A, Lee RP, Sartippour M, Harris DM, Rettig M, Suchard MA, Pantuck AJ, Belldegrun A, Heber D. “Pomegranate ellagitannin-derived metabolites inhibit prostate cancer growth and localize to the mouse prostate gland.” J Agric Food Chem. 2007 Aug 28; [Epub ahead of print] Synopsis: This group of researchers has conducted a phase II clinical trial showing that consuming pomegranate juice increased prostate specific antigen doubling time in prostate cancer patients, indicating a positive effect for inhibiting onset of prostate cancer. Ellagitannins are the most abundant phenolics in pomegranate juice. This study showed that ellagitannin metabolites were concentrated at higher levels in mouse prostate, colon, and intestinal tissues than in other organs after administration of pomegranate extracts. The pomegranate extracts also significantly inhibited growth of cancer cells in mice. Pomegranate urolithins were shown to inhibit the growth of human prostate cancer cells in vitro. The chemopreventive potential of pomegranate ellagitannins and localization of their bioactive metabolites in the mouse prostate indicates that pomegranate phenolics may play a role in human prostate cancer treatment and chemoprevention.

3. Reddy MK, Gupta SK, Jacob MR, Khan SI, Ferreira D. “Antioxidant, antimalarial and antimicrobial activities of tannin-rich fractions, ellagitannins and phenolic acids from Punica granatum L.” Planta Med. 2007 May;73(5):461-7. Synopsis: Phenolic chemicals found in pomegranate—ellagic acid, gallagic acid, punicalins, punicalagins and tannins—were shown in this study to have antioxidant, antiplasmodial, and antimicrobial activities in vitro. Specifically, pomegranate gallagic acid and punicalagins exhibited antimalariial activity against Plasmodium falciparum and all pomegranate phenolics were effective for antimicrobial activity when assayed against E. coli, Pseudomonas aeruginosa, Candida albicans, Cryptococcus neoformans, methicillin-resistant Staphylococcus aureus, Aspergillus fumigatus and Mycobacterium intracellulare. This is the first report on the antioxidant, antiplasmodial and antimicrobial activities of pomegranate isolates, indicating a potential benefit from regular intake of pomegranate products as dietary supplements to augment human immune, antioxidant, antimalarial and antimicrobial capacities.

The research trends for pomegranate show development toward defining anti-disease properties mainly of the phenolics present in the seed arils and juice as the main consumer product. Although the range and depth of research interests are greater than for any other superfruit, understanding about pomegranate’s health properties is still preliminary to human clinical trials which are just now underway. Consequently, several more years of human research will be needed before confirming effects for consumers.

Seaberry (Hippophae rhamnoides L.): Beginning in 1951, there have been 175 medical research reports on seaberry (search PubMed for “sea buckthorn” and “rhamnoides”).

1. Hosseinian FS, Li W, Hydamaka AW, Tsopmo A, Lowry L, Friel J, Beta T. “Proanthocyanidin profile and ORAC values of Manitoba berries, chokecherries, and seabuckthorn.” J Agric Food Chem. 2007 Aug 22;55(17):6970-6. Synopsis: These investigators examined phytochemical content and antioxidant activity in whole fruit, juice, and pulp of six berry species—strawberry, Saskatoon berry, raspberry, wild blueberry, chokecherry, and seaberry. The total proanthocyanidin contents varied from 276 to 505 mg/100 g in the whole fruit samples, with raspberry containing the highest content and seaberry the lowest for total flavanols. The highest concentration of proanthocyanidin in juice was found in Saskatoon berry (1363 mg/100 mL). Epicatechin was the most abundant flavanol among these berries. Lipophilic and hydrophilic antioxidant capacities of whole fruit, juice, and pulp extracts were measured by oxygen radical absorbance capacity (ORAC).

2. Chawla R, Arora R, Singh S, Sagar RK, Sharma RK, Kumar R, Sharma A, Gupta ML, Singh S, Prasad J, Khan HA, Swaroop A, Sinha AK, Gupta AK, Tripathi RP, Ahuja PS. “Radioprotective and antioxidant activity of fractionated extracts of berries of Hippophae rhamnoides.” J Med Food. 2007 Mar;10(1):101-9. Synopsis: The flavonoid-rich fraction of seaberries exhibited strong antioxidant activity and membrane protection of cells in vitro, indicating its ability to scavenge peroxyl radicals. Compared to vitamin E, the fraction also demonstrated efficacy in protecting cells against radiation damage. Such activities were attributed to the presence of quercetin, isorhamnetin, and kaempferol. The seaberry extract has potential as an effective antioxidant nutraceutical product.

3. Teng BS, Lu YH, Wang ZT, Tao XY, Wei DZ. “In vitro anti-tumor activity of isorhamnetin isolated from Hippophae rhamnoides L. against BEL-7402 cells.” Pharmacol Res. 2006 Sep;54(3):186-94. Synopsis: Isorhamnetin, a flavonol aglycone isolated from seaberry, was investigated for its influence on human liver carcinoma cells. The studies showed that isorhamnetin could permeate the cell membrane of the experimental cancer cells, causing fragmentation and stimulated apoptosis (increased rate of cancer cell death). This appears to be the first report of toxicity against human liver carcinoma cells by isorhamnetin, providing a lead toward further research on the anti-cancer properties of seaberry and other pigment-rich berries.

In conclusion, all of the published work on these fruits addresses fundamentals for defining properties in a new research field—first, isolation studies are done to characterize individual phytochemicals, and second, in vitro assays or animal models may be used to identify biological effects.

Such research defines these fruits at the earliest stages of physiological understanding. Consequently, inferences about anti-disease effects or human health benefits are premature and not appropriate at this stage.

The overall totality of research on any one superfruit—even for pomegranate as the most advanced of these six superfruits—is not yet sufficiently broad to invite expert opinion on the developing research base for relevance to human health. In other words, a critical mass of research evidence has not yet occurred (emerging for pomegranate) to allow scientific validation that defines nutrient and phytochemical qualities for guiding consumers about health benefits.

Although begun for pomegranate, but still in the earliest phases, clinical trials for this group of fruits are not yet completed, indicating that confirmable human health effects of these fruits are many years away.

Paul Gross, Ph.D., received his doctorate in physiology from the University of Glasgow and was trained in neuroscience at the Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, Md. He was a Research Scholar for the Heart and Stroke Foundation of Ontario and recipient of the Karger Memorial Award, Switzerland, for publications on brain capillaries. He is also senior author of “Wolfberry: Nature’s Bounty of Nutrition and Health” (Booksurge Publishing, 2006).