Health benefits of anthocyanins and molecular mechanisms: Update from recent decade

Critical Reviews in Food Science and Nutrition

Volumn 57, Issue 8, 2017, Pages 1729-1741

  Li, Daotong ^a   Wang, Pengpu ^a   Luo, Yinghua ^b   Zhao, Mengyao ^a   Chen, Fang ^a  

^a CHINA AGRICULTURAL UNIVERSITY   (China)

^b UNIVERSITY OF MARYLAND   (United States)

Author keywords

Anthocyanins; anti cancer activity; anti inflammation activity; benefits; mechanism; neuroprotective activity

Indexed keywords

ANTHOCYANINS; CELL DEATH; CELL SIGNALING; ENZYME ACTIVITY; ENZYMES; MECHANISMS; PROTEINS;

AMP-ACTIVATED PROTEIN KINASE; ANTI-INFLAMMATION; ANTICANCER ACTIVITIES; BENEFITS; HEALTH BENEFICIAL EFFECTS; MITOGEN ACTIVATED PROTEIN KINASE; NEUROPROTECTIVE ACTIVITY; NUCLEAR FACTOR KAPPAB;

HEALTH;

ANTHOCYANIN; ANTIDIABETIC AGENT; ANTIINFLAMMATORY AGENT; ANTINEOPLASTIC AGENT; ANTIOBESITY AGENT; NEUROPROTECTIVE AGENT;

APOPTOSIS; AUTOPHAGY; CARDIOVASCULAR DISEASES; CELL CYCLE; CHEMISTRY; HUMAN; SIGNAL TRANSDUCTION;

ANTHOCYANINS; ANTI-INFLAMMATORY AGENTS; ANTI-OBESITY AGENTS; ANTINEOPLASTIC AGENTS; APOPTOSIS; AUTOPHAGY; CARDIOVASCULAR DISEASES; CELL CYCLE; HUMANS; HYPOGLYCEMIC AGENTS; NEUROPROTECTIVE AGENTS; SIGNAL TRANSDUCTION;

EID: 85015249287     PISSN: 10408398     EISSN: 15497852     Source Type: Journal    
DOI: 10.1080/10408398.2015.1030064     Document Type: Article

References (102)

1. Afaq, F., Saleem, M., Krueger, C. G., Reed, J. D., and Mukhtar, H., (2005). Anthocyanin- and hydrolyzable tannin-rich pomegranate fruit extract modulates MAPK and NF-kappaB pathways and inhibits skin tumorigenesis in CD-1 mice. Int. J. Cancer. 113:423–433.
2. Akiyama, S., Nesumi, A., Maeda-Yamamoto, M., Uehara, M., and Murakami, A., (2012). Effects of anthocyanin-rich tea “Sunrouge” on dextran sodium sulfate-induced colitis in mice. Biofactors. 38:226–233.
3. Alzaid, F., Cheung, H. M., Preedy, V. R., and Sharp, P. A., (2013). Regulation of glucose transporter expression in human intestinal Caco-2 cells following exposure to an anthocyanin-rich berry extract. PLoS One. 8:e78932.
4. Andersen, Ø. M., (2001). Anthocyanins. John Wiley, Chichester, UK.
5. Andersen, Ø. M., and Markham, K. R., (2006). Flavonoids:Chemistry, Biochemistry, and Applications. CRC, Taylor & Francis, Boca RatonFL.
6. Aqil, F., Gupta, A., Munagala, R., Jeyabalan, J., Kausar, H., Sharma, R. J., Singh, I. P., and Gupta, R. C., (2012). Antioxidant and antiproliferative activities of anthocyanin/ellagitannin-enriched extracts from Syzygium cumini L. (Jamun, the Indian Blackberry). Nutr. Cancer. 64:428–438.
7. Barrios, J., Cordero, C. P., Aristizabal, F., Heredia, F. J., Morales, A. L., and Osorio, C., (2010). Chemical analysis and screening as anticancer agent of anthocyanin-rich extract from Uva Caimarona (Pourouma cecropiifolia Mart.) fruit. J. Agric. Food Chem. 58:2100–2110.
8. Bishayee, A., Háznagy-Radnai, E., Mbimba, T., Sipos, P., Morazzoni, P., Darvesh, A. S., Bhatia, D., and Hohmann, J., (2010). Anthocyanin-rich black currant extract suppresses the growth of human hepatocellular carcinoma cells. Nat. Prod. Commun. 5:1613–1618.
9. Bishayee, A., Mbimba, T., Thoppil, R. J., Háznagy-Radnai, E., Sipos, P., Darvesh, A. S., Folkesson, H. G., and Hohmann, J., (2011). Anthocyanin-rich black currant (Ribes nigrum L.) extract affords chemoprevention against diethylnitrosamine-induced hepatocellular carcinogenesis in rats. J. Nutr. Biochem. 22:1035–1046.
10. Bobe, G., Wang, B., Seeram, N. P., Nair, M. G., and Bourquin, L. D., (2006). Dietary anthocyanin-rich tart cherry extract inhibits intestinal tumorigenesis in APC (Min) mice fed suboptimal levels of sulindac. J. Agric. Food Chem. 54:9322–9328.
11. Bunea, A., Rugină, D., Sconţa, Z., Pop, R. M., Pintea, A., Socaciu, C., Tăbăran, F., Grootaert, C., Struijs, K., and VanCamp, J., (2013). Anthocyanin determination in blueberry extracts from various cultivars and their antiproliferative and apoptotic properties in B16-F10 metastatic murine melanoma cells. Phytochemistry. 95:436–444.
12. Cassidy, A., Mukamal, K. J., Liu, L., Franz, M., Eliassen, A. H., and Rimm, E. B., (2013). A high anthocyanin intake is associated with a reduced risk of myocardial infarction in young and middle-aged women. Circulation. 127:188–196.
13. Dai, J., Gupte, A., Gates, L., and Mumper, R. J., (2009). A comprehensive study of anthocyanin-containing extracts from selected blackberry cultivars:Extraction methods, stability, anticancer properties and mechanisms. Food Chem. Toxicol. 47:837–847.
14. de Pascual-Teresa, S., (2014). Molecular mechanisms involved in the cardiovascular and neuroprotective effects of anthocyanins. Arch. Biochem. Biophys. 559:68–74.
15. de Pascual-Teresa, S., and Sanchez-Ballesta, M. T., (2008). Anthocyanins:From plant to health. Phytochem. Rev. 7:281–299.
16. Devi, P. S., Kumar, M. S., and Das, S. M., (2011). Evaluation of antiproliferative activity of red sorghum bran anthocyanin on a human breast cancer cell line (mcf-7). Int. J. Breast Cancer. 891481.
17. Edirisinghe, I., Banaszewski, K., Cappozzo, J., Sandhya, K., Ellis, C. L., Tadapaneni, R., Kappagoda, C. T., and Burton-Freeman, B. M., (2011). Strawberry anthocyanin and its association with postprandial inflammation and insulin. Br. J. Nutr. 106:913–922.
18. Fernandes, I., Faria, A., Calhau, C., de Freitas, V., and Mateus, N., (2014). Bioavailability of anthocyanins and derivatives. J. Funct. Foods. 7:54–66.
19. Filipiak, K., Hidalgo, M., Silvan, J. M., Fabre, B., Carbajo, R. J., Pineda-Lucena, A., Ramos, A., de Pascual-Teresa, B., and de Pascual-Teresa, S., (2014). Dietary gallic acid and anthocyanin cytotoxicity on human fibrosarcoma HT1080 cells. A study on the mode of action. Food Funct. 5:381–389.
20. Forester, S. C., Choy, Y. Y., Waterhouse, A. L., and Oteiza, P. I., (2014). The anthocyanin metabolites gallic acid, 3-O-methylgallic acid, and 2,4,6-trihydroxybenzaldehyde decrease human colon cancer cell viability by regulating pro-oncogenic signals. Mol. Carcinog. 53:432–439.
21. Ghosh, D., and Konishi, T., (2007). Anthocyanins and anthocyanin-rich extracts:Role in diabetes and eye function. Asia. Pac. J. Clin. Nutr. 16:200–208.
22. Graf, D., Seifert, S., Jaudszus, A., Bub, A., and Watzl, B., (2013). Anthocyanin-rich juice lowers serum cholesterol, leptin, and resistin and improves plasma fatty acid composition in Fischer rats. PLoS One. 8:e66690.
23. Guo, H., Guo, J., Jiang, X., Li, Z., and Ling, W., (2012). Cyanidin-3-O-β-glucoside, a typical anthocyanin, exhibits antilipolytic effects in 3T3-L1 adipocytes during hyperglycemia:Involvement of FoxO1-mediated transcription of adipose triglyceride lipase. Food Chem. Toxicol. 50:3040–3047.
24. Guo, H., Li, D., Ling, W., Feng, X., and Xia, M., (2011). Anthocyanin inhibits high glucose-induced hepatic mtGPAT1 activation and prevents fatty acid synthesis through PKCζ. J. Lipid Res. 52:908–922.
25. Guo, H., Ling, W., Wang, Q., Liu, C., Hu, Y., Xia, M., Feng, X., and Xia, X., (2007). Effect of anthocyanin-rich extract from black rice (Oryza sativa L. indica) on hyperlipidemia and insulin resistance in fructose-fed rats. Plant Foods Hum. Nutr. 62:1–6.
26. Hagiwara, A., Miyashita, K., Nakanishi, T., Sano, M., Tamano, S., Kadota, T., Koda, T., Nakamura, M., Imaida, K., Ito, N., and Shirai, T., (2001). Pronounced inhibition by a natural anthocyanin, purple corn color, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-associated colorectal carcinogenesis in male F344 rats pretreated with 1,2-dimethylhydrazine. Cancer Lett. 171:17–25.
27. Hassimotto, N. M., Moreira, V., do Nascimento, N. G., Souto, P. C., Teixeira, C., and Lajolo, F. M., (2013). Inhibition of carrageenan-induced acute inflammation in mice by oral administration of anthocyanin mixture from wild mulberry and cyanidin-3-glucoside. Biomed. Res. Int. 146716.
28. He, J., and Giusti, M. M., (2010). Anthocyanins:Natural colorants with health-promoting properties. Annu. Rev. Food. Sci. Technol. 1:163–187.
29. Hou, D. X., Yanagita, T., Uto, T., Masuzaki, S., and Fujii, M., (2005). Anthocyanidins inhibit cyclooxygenase-2 expression in LPS-evoked macrophages:Structure-activity relationship and molecular mechanisms involved. Biochem. Pharmacol. 70:417–425.
30. Hui, C., Bin, Y., Xiaoping, Y., Long, Y., Chunye, C., Mantian, M., and Wenhua, L., (2010). Anticancer activities of an anthocyanin-rich extract from black rice against breast cancer cells in vitro and in vivo. Nutr. Cancer. 62:1128–1136.
31. Hung, T. C., Chang, T. T., Fan, M. J., Lee, C. C., and Chen, C. Y., (2014). In Silico insight into potent of anthocyanin regulation of FKBP52 to prevent Alzheimer's disease. Evid. Based Complement. Alternat. Med. 450592.
32. Hwa, K. S., Chung, D. M., Chung, Y. C., and Chun, H. K., (2011). Hypouricemic effects of anthocyanin extracts of purple sweet potato on potassium oxonate-induced hyperuricemia in mice. Phytother. Res. 25:1415–1417.
33. Jang, H., Ha, U. S., Kim, S. J., Yoon, B. I., Han, D. S., Yuk, S. M., and Kim, S. W., (2010). Anthocyanin extracted from black soybean reduces prostate weight and promotes apoptosis in the prostatic hyperplasia-induced rat model. J. Agric. Food Chem. 58:12686–12691.
34. Jing, P., Bomser, J. A., Schwartz, S. J., He, J., Magnuson, B. A., and Giusti, M. M., (2008). Structure–function relationships of anthocyanins from various anthocyanin-rich extracts on the inhibition of colon cancer cell growth. J. Agric. Food Chem. 56:9391–9398.
35. Jurgoński, A., Juśkiewicz, J., and Zduńczyk, Z., (2013). An anthocyanin-rich extract from Kamchatka honeysuckle increases enzymatic activity within the gut and ameliorates abnormal lipid and glucose metabolism in rats. Nutrition. 29:898–902.
36. Kao, E. S., Tseng, T. H., Lee, H. J., Chan, K. C., and Wang, C. J., (2009). Anthocyanin extracted from Hibiscus attenuate-oxidized, LDL-mediated foam cell formation involving regulation of CD36 gene. Chem. Biol. Interact. 179:212–218.
37. Kay, C. D., (2006). Aspects of anthocyanin absorption, metabolism and pharmacokinetics in humans. Nutr. Res. Rev. 19:137–46.
38. Kim, K. T., Nam, T. K., Park, Y. S., Kim, Y. B., and Park, S. W., (2011). Neuroprotective effect of anthocyanin on experimental traumatic spinal cord injury. J. Korean. Neurosurg. Soc. 49:205–211.
39. Kim, Y. K., Yoon, H. H., Lee, Y. D., Youn, D. Y., Ha, T. J., Kim, H. S., and Lee, J. H., (2012). Anthocyanin extracts from black soybean (Glycine max L.) protect human glial cells against oxygen--glucose deprivation by promoting autophagy. Biomol. Ther. 20:68–74.
40. Kocic, B., Filipovic, S., Nikolic, M., and Petrovic, B., (2011). Effects of anthocyanins and anthocyanin-rich extracts on the risk for cancers of the gastrointestinal tract. J. BUON. 16:602–608.
41. Koide, T., Hashimoto, Y., Kamei, H., Kojima, T., Hasegawa, M., and Terabe, K., (1997). Antitumor effect of anthocyanin fractions extracted from red soybeans and red beans in vitro and in vivo. Cancer Biother. Radiopharm. 12:277–280.
42. Koide, T., Kamei, H., Hashimoto, Y., Kojima, T., and Hasegawa, M., (1996). Antitumor effect of hydrolyzed anthocyanin from grape rinds and red rice. Cancer Biother. Radiopharm. 11:273–277.
43. Konczak-Islam, I., Yoshimoto, M., Hou, D. X., Terahara, N., and Yamakawa, O., (2003). Potential chemopreventive properties of anthocyanin-rich aqueous extracts from in vitro produced tissue of sweetpotato (Ipomoea batatas L.). J. Agric. Food Chem. 51:5916–5922.
44. Lala, G., Malik, M., Zhao, C., He, J., Kwon, Y., Giusti, M. M., and Magnuson, B. A., (2006). Anthocyanin-rich extracts inhibit multiple biomarkers of colon cancer in rats. Nutr. Cancer. 54:84–93.
45. Li, L., Wang, L., Wu, Z., Yao, L., Wu, Y., Huang, L., Liu, K., Zhou, X., and Gou, D., (2014). Anthocyanin-rich fractions from red raspberries attenuate inflammation in both RAW264.7 macrophages and a mouse model of colitis. Sci. Rep. 4:6234.
46. Li, G., Zhu, Y., Zhang, Y., Lang, J., Chen, Y., and Ling, W., (2013). Estimated daily flavonoid and stilbene intake from fruits, vegetables, and nuts and associations with lipid profiles in Chinese adults. J. Acad. Nutr. Diet. 113:786–794.
47. Lim, S., Xu, J., Kim, J., Chen, T. Y., Su, X., Standard, J., Carey, E., Griffin, J., Herndon, B., Katz, B., Tomich, J., and Wang, W., (2013). Role of anthocyanin-enriched purple-fleshed sweet potato p40 in colorectal cancer prevention. Mol. Nutr. Food Res. 57:1908–1917.
48. Liu, L. K., Lee, H. J., Shih, Y. W., Chyau, C. C., and Wang, C. J., (2008). Mulberry anthocyanin extracts inhibit LDL oxidation and macrophage-derived foam cell formation induced by oxidative LDL. J. Food Sci. 73:H113–H121.
49. Liu, Y., Li, D., Zhang, Y., Sun, R., and Xia, M., (2014). Anthocyanin increases adiponectin secretion and protects against diabetes-related endothelial dysfunction. Am. J. Physiol. Endocrinol. Metab. 306:E975–E988.
50. Longo, L., Platini, F., Scardino, A., Alabiso, O., Vasapollo, G., and Tessitore, L., (2008). Autophagy inhibition enhances anthocyanin-induced apoptosis in hepatocellular carcinoma. Mol. Cancer Ther. 7:2476–2485.
51. Lu, X., Zhou, Y., Wu, T., and Hao, L., (2014). Ameliorative effect of black rice anthocyanin on senescent mice induced by d-galactose. Food Funct. 5:2892–2897.
52. Malik, M., Zhao, C., Schoene, N., Guisti, M. M., Moyer, M. P., and Magnuson, B. A., (2003). Anthocyanin-rich extract from Aronia meloncarpa E induces a cell cycle block in colon cancer but not normal colonic cells. Nutr. Cancer. 46:186–196.
53. Mauray, A., Felgines, C., Morand, C., Mazur, A., Scalbert, A., and Milenkovic, D., (2010). Nutrigenomic analysis of the protective effects of bilberry anthocyanin-rich extract in apo E-deficient mice. Genes Nutr. 5:343–353.
54. Mauray, A., Felgines, C., Morand, C., Mazur, A., Scalbert, A., and Milenkovic, D., (2012). Bilberry anthocyanin-rich extract alters expression of genes related to atherosclerosis development in aorta of apo E-deficient mice. Nutr. Metab. Cardiovasc. Dis. 22:72–80.
55. Mazza, G., and Miniati, E., (1993). Anthocyanins in Fruits, Vegetables, and Grains. CRC Press, Boca Raton, FL.
56. McGhie, T. K., and Walton, M. C., (2007). The bioavailability and absorption of anthocyanins:Towards a better understanding. Mol. Nutr. Food Res. 51:702–713.
57. Min, J., Yu, S. W., Baek, S. H., Nair, K. M., Bae, O. N., Bhatt, A., Kassab, M., Nair, M. G., and Majid, A., (2011). Neuroprotective effect of cyanidin-3-O-glucoside anthocyanin in mice with focal cerebral ischemia. Neurosci. Lett. 500:157–161.
58. Mink, P. J., Srafford, C. G., Barraj, L. M., Harnack, L., Hong, C. P., Nettleton, J. A., and Jacobs, D. R., (2007). Flavonoid intake and cardiovascular disease mortality:A prospective study in postmenopausal women. Am. J. Clin. Nutr. 85:895–909.
59. Miyake, S., Takahashi, N., Sasaki, M., Kobayashi, S., Tsubota, K., and Ozawa, Y., (2012). Vision preservation during retinal inflammation by anthocyanin-rich bilberry extract:Cellular and molecular mechanism. Lab. Invest. 92:102–109.
60. Mpiana, P. T., Ngbolua, K. N., Bokota, M. T., Kasonga, T. K., Atibu, E. K., Tshibangu, D. S., and Mudogo, V., (2010). In vitro effects of anthocyanin extracts from Justicia secunda Vahl on the solubility of haemoglobin S and membrane stability of sickle erythrocytes. Blood Transfus. 8:248–254.
61. Muraki, I., Imamura, F., Manson, J. E., Hu, F. B., Willett, W. C., van Dam, R. M., and Sun, Q., (2013). Fruit consumption and risk of type 2 diabetes:Results from three prospective longitudinal cohort studies. BMJ. 347:f5001.
62. NHANES. (2001). National Health and Nutrition Examination Survey Data. NHANES, Hyattsville, MD.
63. Paixão, J., Dinis, T. C., and Almeida, L. M., (2011). Dietary anthocyanins protect endothelial cells against peroxynitrite-induced mitochondrial apoptosis pathway and Bax nuclear translocation:An in vitro approach. Apoptosis. 16:976–989.
64. Park, S. Y., Lee, Y. K., Lee, W. S., Park, O. J., and Kim, Y. M., (2014). The involvement of AMPK/GSK3-beta signals in the control of metastasis and proliferation in hepato-carcinoma cells treated with anthocyanins extracted from Korea wild berry Meoru. BMC Complement Altern. Med. 14:109.
65. Peiffer, D. S., Zimmerman, N. P., Wang, L. S., Ransom, B. W., Carmella, S. G., Kuo, C. T., Siddiqui, J., Chen, J. H., Oshima, K., Huang, Y. W., Hecht, S. S., and Stoner, G. D., (2014). Chemoprevention of esophageal cancer with black raspberries, their component anthocyanins, and a major anthocyanin metabolite, protocatechuic acid. Cancer Prev. Res. 6:574–584.
66. Poulose, S. M., Fisher, D. R., Larson, J., Bielinski, D. F., Rimando, A. M., Carey, A. N., Schauss, A. G., and Shukitt-Hale, B., (2012). Anthocyanin-rich açai (Euterpe oleracea Mart.) fruit pulp fractions attenuate inflammatory stress signaling in mouse brain BV-2 microglial cells. J. Agric. Food Chem. 60:1084–1093.
67. PrRimm, E. B., Giovannucci, E. L., Willett, W. C., Colditz, G. A., Ascherio, A., Rosner, B., and Stampfer, M. J., (1991). Prospective study of alcohol consumption and risk of coronary disease in men. Lancet. 338:464–468.
68. Reddivari, L., Vanamala, J., Chintharlapalli, S., Safe, S. H., and Miller, J. C., Jr. (2007). Anthocyanin fraction from potato extracts is cytotoxic to prostate cancer cells through activation of caspase-dependent and caspase-independent pathways. Carcinogenesis. 28:2227–2235.
69. Rugină, D., Sconţa, Z., Leopold, L., Pintea, A., Bunea, A., and Socaciu, C., (2012). Antioxidant activities of chokeberry extracts and the cytotoxic action of their anthocyanin fraction on HeLa human cervical tumor cells. J. Med. Food. 15:700–706.
70. Samuels, T. L., Pearson, A. C., Wells, C. W., Stoner, G. D., and Johnston, N., (2013). Curcumin and anthocyanin inhibit pepsin-mediated cell damage and carcinogenic changes in airway epithelial cells. Ann. Otol. Rhinol. Laryngol. 122:632–641.
71. Shih, P. H., Chan, Y. C., Liao, J. W., Wang, M. F., and Yen, G. C., (2010). Antioxidant and cognitive promotion effects of anthocyanin-rich mulberry (Morus atropurpurea L.) on senescence-accelerated mice and prevention of Alzheimer's disease. J. Nutr. Biochem. 21:598–605.
72. Singletary, K. W., Jung, K. J., and Giusti, M., (2007). Anthocyanin-rich grape extract blocks breast cell DNA damage. J. Med. Food. 10:244–251.
73. Sohn, D. W., Bae, W. J., Kim, H. S., Kim, S. W., and Kim, S. W., (2014). The anti-inflammatory and antifibrosis effects of anthocyanin extracted from black soybean on a peyronie disease rat model. Urology. 84:1112–1116.
74. Srivastava, A., Akoh, C. C., Fischer, J., and Krewer, G., (2007). Effect of anthocyanin fractions from selected cultivars of Georgia-grown blueberries on apoptosis and phase II enzymes. J. Agric. Food Chem. 55:3180–3185.
75. Strathearn, K. E., Yousef, G. G., Grace, M. H., Roy, S. L., Tambe, M. A., Ferruzzi, M. G., Wu, Q. L., Simon, J. E., Lila, M. A., and Rochet, J. C., (2014). Neuroprotective effects of anthocyanin- and proanthocyanidin-rich extracts in cellular models of Parkinson's disease. Brain Res. 1555:60–77.
76. Takikawa, M., Inoue, S., Horio, F., and Tsuda, T., (2010). Dietary anthocyanin-rich bilberry extract ameliorates hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase in diabetic mice. J. Nutr. 140:527–533.
77. Tall, J. M., Seeram, N. P., Zhao, C., Nair, M. G., Meyer, R. A., and Raja, S. N., (2004). Tart cherry anthocyanins suppress inflammation-induced pain behavior in rat. Behav. Brain Res. 153:181–188.
78. Taverniti, V., Fracassetti, D., Del Bo’, C., Lanti, C., Minuzzo, M., Klimis-Zacas, D., Riso, P., and Guglielmetti, S., (2014). Immunomodulatory effect of a wild blueberry anthocyanin-rich extract in human Caco-2 intestinal cells. J. Agric. Food Chem. 62:8346–8351.
79. Tsai, T. C., Huang, H. P., Chang, Y. C., and Wang, C. J., (2014). An anthocyanin-rich extract from Hibiscus sabdariffa linnaeus inhibits N-nitrosomethylurea-induced leukemia in rats. J. Agric. Food Chem. 62:1572–1580.
80. Tsuda, T., Horio, F., and Osawa, T., (2002). Cyanidin 3-O-beta-Dglucoside suppresses nitric oxide production during a zymosan treatment in rats. J. Nutr. Sci. Vitaminol. (Tokyo). 48:305–310.
81. Tsuda, T., Ueno, Y., Aoki, H., Koda, T., Horio, F., Takahashi, N., Kawada, T., and Osawa, T., (2004). Anthocyanin enhances adipocytokine secretion and adipocyte-specific gene expression in isolated rat adipocytes. Biochem. Biophys. Res. Commun. 316:149–157.
82. Vepsäläinen, S., Koivisto, H., Pekkarinen, E., Mäkinen, P., Dobson, G., McDougall, G. J., Stewart, D., Haapasalo, A., Karjalainen, R. O., Tanila, H., and Hiltunen, M., (2013). Anthocyanin-enriched bilberry and blackcurrant extracts modulate amyloid precursor protein processing and alleviate behavioral abnormalities in the APP/PS1 mouse model of Alzheimer's disease. J. Nutr. Biochem. 24:360–370.
83. Wallace, T. C., (2011). Anthocyanins in cardiovascular disease. Adv. Nutr. 2:1–7.
84. Wang, J., Ma, C., Rong, W., Jing, H., Hu, X., Liu, X., Jiang, L., Wei, F., and Liu, Z., (2012a). Bog bilberry anthocyanin extract improves motor functional recovery by multifaceted effects in spinal cord injury. Neurochem. Res. 37:2814–2825.
85. Wang, L. S., and Stoner, G. D., (2008). Anthocyanins and their role in cancer prevention. Cancer Lett. 269:281–290.
86. Wang, D., Xia, M., Yan, X., Li, D., Wang, L., Xu, Y., Jin, T., and Ling, W., (2012b). Gut microbiota metabolism of anthocyanin promotes reverse cholesterol transport in mice via repressing miRNA-10b. Circ Res. 111:967–981.
87. Wang, C., Yatsuya, H., Tamakoshi, K., Uemura, M., Li, Y., Wada, K., Yamashita, K., Kawaguchi, L., Toyoshima, H., and Aoyama, A., (2013). Positive association between high-sensitivity C-reactive protein and incidence of type 2 diabetes mellitus in Japanese workers:6-year follow-up. Diabetes. Metab. Res. Rev. 29:398–405.
88. Welch, C. R., Wu, Q., and Simon, J. E., (2008). Recent advances in anthocyanin analysis and characterization. Curr. Anal. Chem. 4:75–101.
89. Wu, X., Beecher, G. R., Holden, J. M., Haytowitz, D. B., Gebhardt, S. E., and Prior, R. L., (2006). Concentrations of anthocyanins in common foods in the United States and estimation of normal consumption. J. Agric. Food Chem. 54:4069–4075.
90. Wu, T., Yu, Z., Tang, Q., Song, H., Gao, Z., Chen, W., and Zheng, X., (2013). Honeysuckle anthocyanin supplementation prevents diet-induced obesity in C57BL/6 mice. Food Funct. 4:1654–1661.
91. Xia, X., Ling, W., Ma, J., Xia, M., Hou, M., Wang, Q., Zhu, H., and Tang, Z., (2006). An anthocyanin-rich extract from black rice enhances atherosclerotic plaque stabilization in apolipoprotein E-deficient mice. J. Nutr. 136:2220–2225.
92. Xia, M., Ling, W., Zhu, H., Ma, J., Wang, Q., Hou, M., Tang, Z., Guo, H., Liu, C., and Ye, Q., (2009). Anthocyanin attenuates CD40-mediated endothelial cell activation and apoptosis by inhibiting CD40-induced MAPK activation. Atherosclerosis. 202:41–47.
93. Xia, M., Ling, W., Zhu, H., Wang, Q., Ma, J., Hou, M., Tang, Z., Li, L., and Ye, Q., (2007). Anthocyanin prevents CD40-activated proinflammatory signaling in endothelial cells by regulating cholesterol distribution. Arterioscler. Thromb. Vasc. Biol. 27:519–524.
94. Xiao, J. B., and Högger, P., (2015). Dietary polyphenols and type 2 diabetes:Current insights and future perspectives. Curr. Med. Chem. 22:23–38.
95. Ye, J., Meng, X., Yan, C., and Wang, C., (2010). Effect of purple sweet potato anthocyanins on beta-amyloid-mediated PC-12 cells death by inhibition of oxidative stress. Neurochem. Res. 35:357–365.
96. Yoon, B. I., Bae, W. J., Choi, Y. S., Kim, S. J., Ha, U. S., Hong, S. H., Sohn, D. W., and Kim, S. W., (2013). The anti-inflammatory and antimicrobial effects of anthocyanin extracted from black soybean on chronic bacterial prostatitis rat model. Chin. J. Integr. Med. 14.
97. You, J., Kim, J., Lim, J., and Lee, E., (2010). Anthocyanin stimulates in vitro development of cloned pig embryos by increasing the intracellular glutathione level and inhibiting reactive oxygen species. Theriogenology. 74:777–785.
98. Youdim, K. A., Shukitt-Hale, B., and Joseph, J. A., (2004). Flavonoids and the brain:Interactions at the blood-brain barrier and their physiological effects on the central nervous system. Free Radic. Biol. Med. 37:1683–1693.
99. Zapolska-Downar, D., Nowicka, G., Sygitowicz, G., and Jarosz, M., (2008). Anthocyanin-rich aronox extract from Aronia melanocarpa E protects against 7 beta-hydroxycholesterol-induced apoptosis of endothelial cells. Ann. Nutr. Metab. 53:283–294.
100. Zhao, C., Giusti, M. M., Malik, M., Moyer, M. P., and Magnuson, B. A., (2004). Effects of commercial anthocyanin-rich extracts on colonic cancer and nontumorigenic colonic cell growth. J. Agric. Food Chem. 52:6122–6128.
101. Zhu, Y., Ling, W., Guo, H., Song, F., Ye, Q., Zou, T., Li, D., Zhang, Y., Li, G., Xiao, Y., Liu, F., Li, Z., Shi, Z., and Yang, Y., (2013). Anti-inflammatory effect of purified dietary anthocyanin in adults with hypercholesterolemia:A randomized controlled trial. Nutr. Metab. Cardiovasc. Dis. 23:843–849.
102. Zhu, Y., Xia, M., Yang, Y., Liu, F., Li, Z., Hao, Y., Mi, M., Jin, T., and Ling, W., (2011). Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals. Clin. Chem. 57:1524–1533.