see Vitamin C
Asparagus
see also Rutin Asparagus (Asparagus officinalis) is readily available in grocery stores as canned or freshly packed. The major flavonoid in asparagus is rutin, which is a strong antioxidant (Makris and Rossiter, 2001). Earlier work by Vinson et al. (1998) showed asparagus ranked fourth out of 23 vegetables in the amount of total phenols, but first for antioxidant
Rutin. (Adapted from Deng et al., Radiat. Phys. Chem., 53:629–633, 1998.)
quality. Makris and Rossiter (2001) examined the effect of processing on the flavonol and antioxidant status of asparagus spears. The predominant flavonol was rutin, although a few minor peaks were also observed. The effect of processing is summarized in Table A.6. Boiling was a far more destructive process compared to chopping, with rutin losses being 18.5 percent and 43.9 percent for boiling and chopping, respectively.
Jang and coworkers (2004) recently isolated and characterized a number of natural chemopreventive agents from an ethyl acetate-soluble fraction of the methanol extract of the aerial parts of asparagus (Asparagus officinalis). Of 16 compounds identified, two were new natural products, asparagusic acid anti-S-oxide methyl ester and asparagusic acid syn-S-oxide methyl ester plus a new acetylenic compound, 2-hydroxyasaparenyn {3′,4′-trans-2-hydroxy-1-methoxy-4-[5-(4-methoxyphenoxy)-3-penten-1-ynyl]-benzene}.
Of all the compounds identified, linoleic acid showed the most significant activity against COX-2 and moderate activity against COX-1 (Table A.7). Of the remainder, (±)-1-hexadececanoylglycerol (6) exhibited weak activity against COX-1 and moderate activity against COX-2, while ferulic acid (7),
TABLE A.6
Effect of Domestic Processes on Rutin Content of Asparagus1
Chopping Boiling
Compound Control Chopped Percent
Change Control Chopped Percent Change Rutin 286.5+6.0 233.6+3.5 −18.50 percent 274.1+3.8 153.7+5.5 −43.90 percent
1Data expressed as mgkg−1
Source: Adapted from Makris and Rossiter, J. Agric. Food Chem., 49:3216–3222, 2001.
TABLE A.7
Inhibitory Activities of Compounds from A. Officinalis Against Cyclooxygenase-1 and -2a
Linoleic acid 100 14.6 100 0.53
trans-resveratrolb 100 0.25 100 0.30
aND Not determined.
btrans-Resveratrol was used as a positive control.
Source: From Jang et al., J. Agric. Food Chem., 52:2218–2222, 2004. With permission
1,3-O-di-p-coumaroylglycerol (8) and 1-O-feruloyl-3-O-p-coumaroylglycerol (9) had only weak activity against COX-1. Inhibition of cyclooxygenase (COX) enzymes by nonsteroidal anti-inflammatory drugs (NSAIDs) are thought to hinder the development of colon cancer (Chan, 2002).
References
Chan, T.A., Nonsteroidal anti-inflammatory drugs, apoptosis, and colon-cancer chemoprevention, Lancet Oncol., 3:166–174, 2002.
Deng, W., He, Y., Fang, X., and Wu, J., Radiolysis of rutin in aerated ethanolic solution, Radiat.
Phys. Chem., 53:629–633, 1998.
Jang, D.S., Cuendet, M., Fong, H.H.S., Pezzuto, J.M., and Kinghorn, A.D., Constituents of Asparagus officinalis evaluated for inhibitory activity against cyclooxygenase-2, J. Agric. Food Chem., 52:2218–2222, 2004.
Makris, D.P. and Rossiter, J.T., Domestic processing of onion bulbs (Allium cepa) and asparagus spears (Asparagus officinalis): Effect on flavonol content and antioxidant status, J. Agric. Food Chem., 49: 3216–3222, 2001.
Vinson, J.A., Hao, Y., Su, X., and Zubik, L., Phenol antioxidant quantity and quality in foods, J.
Agric. Food Chem., 46:3630–3634, 2001.
Astaxanthin
Astaxanthin, a carotenoid pigment, is responsible for the tinted red of crustaceans or the pink flesh of salmon. It is produced commercially worldwide from the microalga Haemastoccus pluvialis (Olaizola
Astaxanthin. (From Lai et al., J. Chromatogr. B., 804:25–30, 2004.
With permission.)
and Huntley, 2002). The structure of astaxanthin is very similar to β-carotene, but it has been shown to be a superior antioxidant (Lawlor and O’Brien, 1995; Palozza and Krinsky, 1992). Astaxanthin has also been shown to protect the skin and eyes from UV light (Papas, 1999). Other carotenoids, lutein and zeaxanthin, which are also structurally related to astaxanthin, do not have its strong antioxidant activity and UV-light-protective properties (O’Connor and O’Brien, 1998). When fed to humans at doses as low as 3.6 mg per day for two consecutive weeks, astaxanthin protected LDL cholesterol from induced in vitro oxidation (Miki et al., 1998). Jacobsson et al. (2004) found that LDL-oxidation time was significantly prolonged in Watanabe heritable hyperlipidemia (WHHL) rabbits in the presence of α-tocopherol but unaffected when treated with astaxanthin. However, the antioxidant treatment produced smaller lesions and intimal thickening. Further examination of atheroma by Li and coworkers (2004) showed astaxanthin had a protective role by reducing macrophage infiltration and modulated macrophage apoptosis and MMP3. A similar effect was evident for α-tocopherol, which suggested these antioxidants are both antiatherogenic, since lipid and macrophage infiltration is closely associated with early plaque development.
Astaxanthin has also been reported to significantly inhibit colon cancer in rats, as well as the enzyme 5-α-reductase involved in prostate growth (Anderson, 2001). The ability of
astaxanthin to cross the blood-brain barrier in rats suggests it might be beneficial to neurological diseases, such as Alzheimer’s (Tso and Lam, 1996). Evidence is also accruing regarding the immunomodulating activity of astaxanthin, including enhancement of immunoglobulin production in human blood cells in response to T-dependent stimuli (Jyonouchi et al., 1995). The bioavailability of astaxanthin was demonstrated in humans using a single, high dose of 100 mg and its transport by plasma lipoproteins (Osterlie et al., 2000).
The lipophilic nature of carotenoids, such as astaxanthin, renders it difficult to deliver it to target cells. One way to surmount this problem is to form water-soluble derivatives, such as the disodium salt disuccinate. Hix et al. (2004) showed this astaxanthin derivative was biologically active by upregulating expression of connexin protein (CX43), increasing the formation of CX43 immunoreactive plaques, as well as significantly upregulating intracellular communication. The enhanced delivery of these derivatives suggested greater potential for astaxanthin as an anticancer agent.
References
Anderson, M., Method of inhibiting 5-α reductase with astaxanthin to prevent and treat benign prostate hyperplasia (BPH) and prostrate cancer in human males, US Patent No. 6277417, 2001.
Hix, L.M., Lockwood, S.F., and Bertram, J.S., Upregulation of connexin 43 protein expression and increased gap functional communication by water soluble disodium discuccinate astaxanthin derivatives, Cancer Lett., 211:25–37, 2004.
Jacobsson, L.S., Yuan, Y.-M., Zieden, B., and Olsson, A.G., Effects of α-tocopherol and
astaxanthin on LDL oxidation and atherosclerosis in WHHL rabbits, Atherosclerosis, 173:231–
237, 2004.
Jyonouchi, H., Sun, Y., and Gross, M.D., 1995a. Effect of carotenoids on in vitro immunoglobulin production by human peripheral blood mononuclear cells: Astaxanthin, a carotenoid without vitamin A activity, enhances in vitro immunoglobulin production in response to a T-dependent stimulant and antigen, Nutr. Cancer, 23:171–183, 1995a.
Jyonouchi, H., Sun, Y., Tomita, Y., and Gross, M.D., Astaxanthin, a carotenoid without vitamin A activity, augments antibody responses in cultures including T-helper cell clones and suboptimal doses of antigen, J. Nutr., 124:2483–2493, 1995b.
Lai, J.-P., Jiang, Y., He, X.-W., Huang, J.-C., and Chen, F., Separation and determination of astaxanthin from microalgal and yeast samples by molecularly imprinted microspheres, J.
Chromatogr. B., 804:25–30, 2004.
Lawler, S.M. and O’Brien, N.M., Astaxanthin: Antioxidant effects in chicken embryo fibroblasts, Nutr. Res., 15:1695–1704, 1995.
Li, W., Hellsten, A., Jacobsson, L.S., Blomqvist, H.A., Olsson, A.G., and Yuan, Y.-M., Alpha-tocopherol and astaxanthin decrease macrophage infiltration, apoptosis and vulnerability in atheroma in hyperlipidemia rabbits, J. Mol. Cell. Cardiol., 37: 969–978, 2004.
Miki, W., Hosada, K., and Gross, M., Astaxanthincontaining drink, Japanese Patent No. 10155459, 1998.
O’Connor, I. and O’Brien, N., Modulation of UVA light-induced oxidative stress by beta-carotene, lutein and ataxanthin in cultured fibroblasts, J. Dermatol. Sci., 16:226–230, 1998.
Olaizola, M. and Huntley, M.E., Recent advances in commercial production of astaxanthin from microalgae, in Biomaterials and Bioprocessing, Fingerman, M. and Nagabhushanam, R., Eds., Science Publishers, 9:143–164, 2002.
Osterlie, M., Bjerkeng, B., and Liaaen-Jenoen, S., Plasma appearance and distribution of
astaxanthin E/Z isomers in plasma lipoproteins after a single dose administration of astaxanthin, J. Nutr. Biochem., 11: 482–190, 2000.
Palozza, P. and Krinsky, N.I., Astaxanthin and canxanthin are potent antioxidants in a membrane model, Arch. Biochem. Biophys., 297:291–295, 1992.
Papas, A., Antioxidant Status, Diet, Nutrition and Health, CRC Press, Boca Raton, Florida, 1999.
Tso, M.O.M. and Lam. T.T., Methods of retarding and ameliorating central nervous system and eye damage, U.S. Patent No. 1 5527533, 1996.
Astragalus
Astragalus, a traditional Chinese herb derived from the root of Astragalus membranaceus, has been used to treat diabetes, heart disease, and high blood pressure.
An extract from Astragalus membranaceus was shown by Zhao et al. (1990) to enhance the immune response in mice. Using a large-scale culture technique, Zheng and coworkers (1998) analyzed the hairy roots of Astragalus membranaceus, which contained 5.8 percent and 0.14 percent of crude saponins and astragaloside, respectively. They also demonstrated the ability of the hairy roots to increase immune function. Ma et al. (1998) demonstrated the therapeutic effects of Astragalus membranaceus on sodium and water retention in aortacaval fistulainduced heart failure. A clinical research trial by Zheng et al. (1995) showed astragalus improved the deformability of red blood cells and delayed aging in mice.
References
Ma, J., Peng, A., and Lin, S., Mechanisms of the therapeutic effect of Astragalus membranaceus on sodium and water retention in experimental heart failure, Chin. Med. J., 111:17–23, 1998.
Zhao, K.S., Mancini, C., and Doria, G., Enhancement of the immune response in mice by Astragalus membranaceus, Immunopharmacology, 20:225–233, 1990.
Zheng, Z., Dai, J., and Zhu, M., Effect of injection of Astragalus membranaceus on the deformability of red blood cells, Biorheology, 32:322-, 1995.
Zheng, Z., Liu, D., Cheng, C., and Hu, Z., Studies on chemical constituents and immunological function activity of hairy roots of Astragalus membranaceus, Chin. J. Biotechnol., 14:93–97, 1998.
Auraptene
Auraptene (7-geranylcoumarin) is a natural component of citrus peel with chemoprotective properties against skin, tongue, esophagus, and colon carcinogenesis in rodents (Murakami et al., 1997; Tanaka et al., 1997, 1998a, b).
Auraptene. (From Tanaka et al., Carcinogenesis, 18:2155–2161, 1997.) Tanaka et al. (1997) reported auraptene reduced the number of precancerous lesions in carcinogen-induced rat colons. A single oral dose of auraptene (200 mg/kg body weight) increased the activity of quinone reductase and glutathione S-transferase, two key Phase II detoxifying enzymes. In vivo studies showed auraptene suppressed the generation of superoxide anions (·O2−) from inflammatory leukocytes. Murakami et al. (2004) found the inhibitory effects of auraptene were due to its selective blockage of the activation stage by attenuating the lipopolysaccharide-induced expression of inducible forms of both nitricoxide synthase and cyclooxygenase in a murine macrophage line, RAW 264.7.
It decreased the production of the nitrite anion and prostaglandin E2, while suppressing the release of the tumor necrosis factor-α. The overall effect in vivo in ICR female rats was decreased levels of edema, H2O2 production, leukocyte infiltration, and PCNA-labeling index. In vivo data showed a marked suppression of iNOS/COX-2 expression and TNF-α release. Thus, auraptene could have application in preventing and medicating inflammation-related disorders, such as cancer.
References
Murakami, A., Kuli, W., Takahashi, Y., Yonei, H., Nakamura, Y., Ohto, Y., Ohigashi, H., and Koshimizu, K., Auraptene, a citrus coumarin, inhibits 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in ICR mouse skin, possibly through suppression of superoxide generation in leukocytes, Jpn. J. Cancer Res., 88:443–452, 1997.
Murakami, A., Nakamura, Y., Tanaka, T., Kawabata, K., Takahashi, D., Koshimizu, K., and Ohigashi, H., Suppression by citrus auraptene of phorbol ester- and endoxin-induced inflammatory responses, Carcinogenesis, 21:1843–1850, 2000.
Tanaka, T., Kawabata, K., Kakumoto, M., Hara, A., Mori, H., Satoh, K., Murakami, A., Kuki, W., Takahashi, Y., Yonei, H., Koshimizu, K., and Ohigashi, H., Citrus auraptene inhibits chemically induced colonic aberrant crypt foci in male F344 rats, Carcinogenesis, 18:2155–2161, 1997.
Tanaka, T., Kawabata, K., Kakumoto, M., Hara, A., Murakami, A., Kuki, W., Takahashi, Y., Yonei, H., Maeda, M., Otah, T., Odashima, S., Yamane, T., Koshimizu, K., and Ohigashi, H., Citrus auraptene exerts dose-dependent chemopreventive activity in rat large bowel
tumorigenesis: The inhibition correlates with suppression of cell proliferation and lipid peroxidation and with induction of phase II drug-metabolizing enzymes, Cancer Res., 58:2550–
2556, 1998a.
Tanaka, T., Kawabata, K., Kakumoto, M., Matsunaga, K., Mori, H., Murakami, A., Kuki, W., Takahashi, Y., Yonei, H., Satoh, K., Hara, A., Maeda, M., Otah, T., Odashima, S., Koshimizu, K., and Ohigashi, H., Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by citrus auraptene in rats, Carcinogenesis, 19:425–431, 1998b.
Avocado
Avocado is a type of pear (Persea americana) originating in Mexico that is processed for oil. Mexico (34 percent) is the largest producer of avocados, followed by the United States (8 percent), Israel (4 percent), South Africa (2 percent), and, recently, New Zealand (Eyres et al., 2001). Novel nitric-oxide and superoxide generation inhibitors, persenone A and B, were identified in avocado fruit by Kim and coworkers (2000a).
These researchers showed persenone A suppressed expression of
Persenone (From Kim et al., J. Agric. Food Chem., 48:1557–1563, 2000b. With permission.)
both inducible nitric-oxide synthase and COX-2 in mouse macrophages and inhibited H2O2 generation in mouse skin (Kim et al., 2000b). Their results suggest that persenone A may prevent inflammation-associated diseases, including cancer. Kawagishi and coworkers (2000) isolated five fatty-acid derivatives in avocado that showed extraordinary, potent liver-injury-suppressing activity against liver damage by D-galactosamine, a powerful liver toxin. The oil from avocado is highly valued by the cosmetic industry and in the food industry for the
TABLE A.8
β-Sitosterol of Eight of the Most Frequently Consumed Fruits in the U.S.A.
Fruit1 β-Sitosterol2
(mg/100 g2)
Apples 11
Avocado 76
Banana 11
Cantaloupe 8
Grapefruit 13
Strawberries 10
Sweet Cherries 12
1Raw, edible portion.
2β-Sitosterol values for all fruits, except avocado, Adapted from Moghadasian et al., 1999.
Source: Adapted from Duester, Lipid Tec., 7:84–88, 2001.
beneficial effects of its monounsaturated fatty acid, oleic acid, which accounts for almost 80 percent of the total fatty acids. In addition, avocado oil also contains relatively high amounts of β-sitosterol (0.5–1.0 percent) reported to lower blood cholesterol levels (see Phytosterols). β-Sitosterol has also been attributed to alleviating the symptoms of benign prostatic hypertrophy in men over 50 years of age (Berges et al., 1995). Avocado appears to be one the richest sources of β-sitosterol compared to eight of the most popular fruits consumed in the United States, as seen in Table A.8. Lu and coworkers (2005) showed lipid-soluble bioactives in avocado extract inhibited the growth of prostate-cancer cells.
Avocado was also shown to have important antihyperglycemic properties in humans (Alvizouri-Munoz et al., 1994). Using an in vitro method for assessing glucose diffusion across the gastrointestinal tract, Gallagher and coworkers (2003) showed avocado decreased glucose movement by more than 50 percent. These researchers suggested that avocado could be used as a dietary supplement in the diet of type 2 diabetic subjects.
References
Alvizouri-Munoz, M., Carranza-Madrigal, J., Herrera-Abarca, J.E., Chavez, C.F., and Amezcua-Gastelum, J.L., Effects of avocado as a source of monounsaturated fatty acids on plasma lipid levels, Arch. Med. Res., 23:163–167, 1992.
Berges, R.R., Winderler, J., Trampisch, H.J., Senge, T., and beta-sitosterol study group, Randomized, placebo-controlled, double-blind clinical trial of beta;-sitosterol in patients with benign prostatic hyperplasia, Lancet, 345:1529–1532, 1995.
Duester, K.C., Avocado fruit is the richest source of beta-sitosterol, J. Am. Diet. Assoc., 101:404–
405, 2001.
Eyres, L., Sherpa, S., and Hendriks, G., Avocado oil: A new edible oil from Australia, Lipid Technol., 7:84–88, 2001.
Gallagher, A.M., Flatt, P.R., Duffy, G., and Abdel-Wahab, Y.H.A., The effects of traditional antidiabetic plants on in vitro glucose diffusion, Nutr. Res., 23: 413–424, 2003.
Kawagishi, H., Fukumoto, Y., Hatakeyama, M., He, P.O., Arimoto, H., Matsuzawa, T., Arimoto, Y., Suganuma, H., Inakuma, T., and Sugiyama, K., J. Agric. Food Chem., 49:2215–2221, 2001.
Kim, O.K., Murakami, A., Takahashi, D., Nakamura, Y., Torikai, K., Kim, H.W., and Ohigashi, H., An avocado constituent, persenone A, suppresses expression of inducible forms of nitric oxide synthase and cyclooxygenase in macrophages, and hydrogen peroxide generation in mouse skin, Biosci. Biotechnol. Biochem., 64:2504–2507, 2000a.
Kim, O.K., Murakami, A., Nakamura, Y., Takeda, N., Yoshizumi, H., and Ohigashi, H., Novel nitric oxide and superoxide generation inhibitors, persenone A and B, from avocado fruit, J.
Agric. Food Chem., 48: 1557–1563, 2000b.
Lu, Q.-Y., Arteaga, J.R., Zhang, Q., Huerta, S., Go, V.L.W., and Heber, D., Inhibition of prostate cancer cell growth by an avocado extract: Role of lipidsoluble bioactive substances, J. Nutr.
Biochem., 16: 23–30, 2005.
Moghadisian, M.H. and Frolich, J.J., Effect of dietary phytosterols on cholesterol metabolism and atherosclerosis: Clinical and experimental evidence, Am. J. Med., 107:588–594, 1999.