Abstract:The antioxidant and topical anti-inflammatory activities of low and high molecular weight phenolic fractions (LMPF and HMPF, respectively) isolated from three blackberry cultivars (i.e., Navaho, Kiowa, and Ouachita), bred to tolerate the warm and humid climatic conditions of the southeastern United States, were investigated by the in vitro ferric reducing antioxidant power (FRAP) assay and an in vivo mouse ear edema model. Seventy percent (v/v) acidified acetone was employed to extract phenolics from the Georgia-grown blackberry cultivars, which were subsequently cleaned up on an Amberlite XAD-16 column and then further fractionated with Sephadex LH-20 to LMPF and HMPF. The anti-inflammatory response from topical application of solutions of the LMPF and HMPF as well as indomethacin, a potent nonsteroidal anti-inflammatory drug, was assessed in the TPA mouse ear model. All treatments significantly (P < 0.05) reduced TPA-induced irritation injury. Furthermore, mouse ear myeloperoxidase (MPO) activity, an indicator of polymorphonuclear leukocyte infiltration, was assessed and found to be significantly (P < 0.05) reduced after topical application of indomethacin and all blackberry preparations. Correlation coefficients of 0.925 and 0.923 (P < 0.01) were determined when the anti-inflammatory activities of the blackberry fractions were compared to their total phenolics contents and antioxidant activities (i.e., FRAP values), respectively.

Antioxidant and Anti-inflammatory Activities of Polyphenolics from Southeastern U.S. Range Blackberry Cultivars

Key words: Blackberries; polyphenolics; anti-inflammatory activity; antioxidant activity; edema; myeloperoxidase activity; polymorphonuclear leukocyte infiltration

†Department of Food Science and Technology, College of Agricultural and Environmental Sciences,The University of Georgia, 100 Cedar Street, Athens, Georgia 30602, ‡Department of Pharmaceuticaland Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, Georgia 30602,§Department of Foods and Nutrition, College of Family and Consumer Sciences, The University ofGeorgia, 305 Sanford Drive, Athens, Georgia 30602, and #Division of Food Science, Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, ul. Tuwima 10,10-747 Olsztyn, Poland

ANITA SRIVASTAVA,† PHILLIP GREENSPAN,‡ DIANE K. HARTLE,‡ JAMES L. HARGROVE,§RYSZARD AMAROWICZ,#AND RONALD B. PEGG*,†

注：将上面摘要外文内容复制后，点击翻译助手，最后粘贴内容至翻译框内。

参考文献：

(1) Takachi, R.; Inoue, M.; Ishihara, J.; Kurahashi, N.; Iwasaki, M.; Sasazuki, S.; Iso, H.; Tsubono, Y.; Tsugane, S. Fruit and vegetable intake and risk of total cancer and cardiovascular disease. Am. J. Epidemiol. 2008, 167, 59–70.
(2) Dai, Q.; Borenstein, A. R.; Wu, Y.; Jackson, J. C.; Larson, E. B. Fruit and vegetable juices and Alzheimer’s disease: The Kame project. Am. J. Med. 2006, 119, 751–759.
(3) Nijveldt, R. J.; van Nood, E.; van Hoorn, D. E. C.; Boelens, P. G.; van Norren, K.; van Leeuwen, P. A. M. Flavonoids: a review of probable mechanisms of action and potential applications. Am. J.Clin. Nutr. 2001, 74, 418–425.
(4) Halvorsen, B. L.; Carlsen, M. H.; Phillips, K. M.; Bøhn, S. K.; Holte,K.; Jacobs, D. R., Jr.; Blomhoff, R. Content of redox-active compounds (ie, antioxidants) in foods consumed in the United States. Am. J. Clin. Nutr. 2006, 84, 95–135.

(5) Greenspan, P.; Bauer, J. D.; Pollock, S. H.; Gangemi, J. D.; Mayer,E. P.; Ghaffar, A.; Hargrove, J. L.; Hartle, D. K. Antiinflammatory properties of the muscadine grape (Vitis rotundifolia). J. Agric. Food Chem. 2005, 53, 8481–8484.
(6) Hou, D.-X.; Kai, K.; Li, J.-J.; Lin, S.; Terahara, N.; Wakamatsu, M.; Fujii, M.; Young,M. R.; Colburn, N. Anthocyanidins inhibit activator protein 1 activity and cell transformation: structure-activity relationship and molecular mechanisms. Carcinogenesis 2004, 25, 29–36.
(7) Wang, J.; Mazza, G. Inhibitory effects of anthocyanins and other phenolic compounds on nitric oxide production in LPS/IFN-γ-activated RAW 264.7 macrophages. J. Agric. Food Chem. 2002,50, 850–857.
(8) Kundu, J. K.; Chun, K.-S.; Kim, S. O.; Surh, Y.-J. Resveratrol inhibits phorbol ester-induced cyclooxygenase-2 expression in mouse skin: MAPKs and AP-1 as potential molecular targets. BioFactors 2004, 21, 33–39.
(9) Meeran, S. M.; Mantena, S. K.; Katiyar, S. K. Prevention of ultraviolet radiation-induced immunosuppression by (-)-epigallocatechin-3-gallate in mice is mediated through interleukin 12-dependent DNA repair. Clin. Cancer Res. 2006, 12, 2272–2280.
(10) Tall, J. M.; Seeram, N. P.; Zhao, C.; Nair, M. G.; Meyer, R. A.; Raja,S. N. Tart cherry anthocyanins suppress inflammation-induced pain behavior in rat. Behav. Brain Res. 2004, 153, 181–188.
(11) Afaq, F.; Saleem, M.; Krueger, C. G.; Reed, J. D.; Mukhtar, H. Anthocyanin- and hydrolyzable tannin-rich pomegranate fruit extract modulates MAPK and NF-κB pathways and inhibits skin tumorigenesis in CD-1 mice. Int. J. Cancer 2005, 113, 423–433.
(12) Nauseef, W. M. Contributions of myeloperoxidase to proinflammatory events: more than an antimicrobial system. Int. J. Hematol.2001, 74, 125–133.
(13) Baldus, S.; Heeschen, C.; Meinertz, T.; Zeiher, A. M.; Eiserich, J. P.;M€unzel, T.; Simoons, M. L.; Hamm, C.W. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes.Circulation 2003, 108, 1440–1445.
(14) Kato, Y.; Nagao, A.; Terao, J.; Osawa, T. Inhibition of myeloperoxidase-catalyzed tyrosylation by phenolic antioxidants in vitro.Biosci., Biotechnol., Biochem. 2003, 67, 1136–1139.
(15) Bralley, E. E.; Hargrove, J. L.; Greenspan, P.; Hartle, D. K. Topical anti-inflammatory activities of Vitis rotundifolia (Muscadine grape) extracts in the tetradecanoylphorbol acetate model of ear inflammation.J. Med. Food 2007, 10, 636–642.
(16) Duthie, S. J. Berry phytochemicals, genomic stability and cancer: Evidence for chemoprotection at several stages in the carcinogenic process. Mol. Nutr. Food Res. 2007, 51, 665–674.
(17) Siriwoharn, T.; Wrolstad, R. E.; Finn, C. E.; Pereira, C. B. Influence of cultivar, maturity, and sampling on blackberry (Rubus L. hybrids) anthocyanins, polyphenolics, and antioxidant properties. J. Agric. Food Chem. 2004, 52, 8021–8030.
(18) Seeram, N. P.; Adams, L. S.; Zhang, Y.; Lee, R.; Sand, D.; Scheuller,H. S.; Heber, D. Blackberry, black raspberry, blueberry, cranberry,red raspberry, and strawberry extracts inhibit growth and stimulateapoptosis of human cancer cells in vitro. J. Agric. Food Chem. 2006,54, 9329–9339.
(19) Hagerman, A. E.; Butler, L. G. Protein precipitation method for thequantitative determination of tannins. J. Agric. Food Chem. 1978, 26,809–812.
(20) Singleton, V. L.; Rossi, J. A., Jr. Colorimetry of total phenolics withphosphomolybdic-phosphotungstic acid reagents. Am. J. Enol.Vitic. 1965, 16, 144–158.
(21) Benzie, I. F. F.; Strain, J. J. The ferric reducing ability of plasma(FRAP) as a measure of “antioxidant power”: the FRAP assay.Anal. Biochem. 1996, 239, 70–76.
(22) Dell, R. B.; Holleran, S.; Ramakrishnan, R. Sample size determination.ILAR J. 2002, 43, 207–213.
(23) Suzuki, K.; Ota, H.; Sasagawa, S.; Sakatani, T.; Fujikura, T. Assaymethod for myeloperoxidase in human polymorphonuclear leukocytes.Anal. Biochem. 1983, 132, 345–352.
(24) De Young, L. M.; Kheifets, J. B.; Ballaron, S. J.; Young, J. M.Edema and cell infiltration in the phorbol ester-treated mouse ear aretemporally separate and can be differentially modulated by pharmacologicagents. Agents Actions 1989, 26, 335–341.
(25) Fan-Chiang, H.; Wrolstad, R. E. Anthocyanin pigment compositionof blackberries. J. Food Sci. 2005, 70, C198–C202.
(26) Wang, H.; Cao, G.; Prior, R. L. Total antioxidant capacity of fruits.J. Agric. Food Chem. 1996, 44, 701–705.
(27) Hager, T. J.; Howard, L. R.; Liyanage, R.; Lay, J. O.; Prior, R. L.Ellagitannin composition of blackberry as determined by HPLC-ESIMSand MALDI-TOF-MS. J. Agric. Food Chem. 2008, 56, 661–669.
(28) George´ , S.; Brat, P.; Alter, P.; Amiot, M. J. Rapid determination ofpolyphenols and vitamin C in plant-derived products. J. Agric. FoodChem. 2005, 53, 1370–1373.
(29) Kao,M.-W. S.; Woods, F.M.; Dozier,W. A., Jr.; Ebel, R. C.; Nesbitt,M.; Jee, J.; Fields, D. Phenolic content and antioxidant capacities ofAlabama-grown thornless blackberries. Int. J. Fruit Sci. 2007, 7, 33–46.
(30) Sellappan, S.; Akoh, C. C.; Krewer, G. Phenolic compounds andantioxidant capacity of Georgia-grown blueberries and blackberries.J. Agric. Food Chem. 2002, 50, 2432–2438.
(31) Pellegrini, N.; Serafini, M.; Colombi, B.; del Rio, D.; Salvatore, S.;Bianchi, M.; Brighenti, F. Total antioxidant capacity of plant foods,beverages and oils consumed in Italy assessed by three different invitro assays. J. Nutr. 2003, 133, 2812–2819.
(32) Nishizuka, Y. The role of protein kinase C in cell surface signaltransduction and tumour promotion. Nature 1984, 308, 693–698.
(33) Carlson, R. P.; O’Neill-Davis, L.; Chang, J.; Lewis, A. J. Modulationof mouse ear edema by cyclooxygenase and lipoxygenase inhibitorsand other pharmacologic agents. Agents Actions 1985, 17, 197–204.
(34) Silva, D. H. S.; Zhang, Y.; Santos, L. A.; Bolzani, V. S.; Nair, M. G.Lipoperoxidation and cyclooxygenases 1 and 2 inhibitory compoundsfrom Iryanthera juruensis. J. Agric. Food Chem. 2007, 55, 2569–2574.
(35) Bradley, P. P.; Priebat, D. A.; Christensen, R. D.; Rothstein, G.Measurement of cutaneous inflammation: estimation of neutrophilcontent with an enzymemarker. J. Invest. Dermatol. 1982, 78, 206–209.
(36) Chung, W.-Y.; Jung, Y.-J.; Surh, Y.-J.; Lee, S.-S.; Park, K.-K.Antioxidative and antitumor promoting effects of [6]-paradol and itshomologs. Mutat. Res. 2001, 496, 199–206.
(37) Huang, M.-T.; Liu, Y.; Ramji, D.; Lo, C.-Y.; Ghai, G.; Dushenkov,S.; Ho, C.-T. Inhibitory effects of black tea theaflavin derivatives on12-O-tetradecanoylphorbol-13-acetate-induced inflammation andarachidonic acid metabolism in mouse ears. Mol. Nutr. Food Res.2006, 50, 115–122.
(38) Rocha, J. C. B.; Pedrochi, F.; Hernandes, L.; DeMello, J. C. P.;Baesso, M. L. Ex vivo evaluation of the percutaneous penetration ofproanthocyanidin extracts from Guazuma ulmifolia using photoacousticspectroscopy. Anal. Chim. Acta 2007, 587, 132–136.
(39) Middleton, E., Jr.; Kandaswami, C.; Theoharides, T. C. The effectsof plant flavonoids on mammalian cells: implications for inflammation,heart disease, and cancer. Pharmacol. Rev. 2000, 52, 673–751.
(40) Kwon, J. Y.; Lee, K. W.; Hur, H. J.; Lee, H. J. Peonidin inhibitsphorbol-ester-induced COX-2 expression and transformation in JB6Pþcells by blocking phosphorylation of ERK-1 and -2. Ann. N.Y.Acad. Sci. 2007, 1095, 513–520.
(41) Serraino, I.; Dugo, L.; Dugo, P.;Mondello, L.;Mazzon, E.; Dugo, G.;Caputi, A. P.; Cuzzocrea, S. Protective effects of cyanidin-3-O-glucosidefrom blackberry extract against peroxynitrite-induced endothelialdysfunction and vascular failure. Life Sci. 2003, 73, 1097–1114.
(42) Saklatvala, J.; Dean, J.; Clark, A. Control of the expression ofinflammatory response genes. Biochem. Soc. Symp. 2003, 70, 95–106.
(43) Murphy, J.-E.; Robert, C.; Kupper, T. S. Interleukin-1 and cutaneousinflammation: a crucial link between innate and acquiredimmunity. J. Invest. Dermatol. 2000, 115, 602–608.
(44) Wang, L.-S.; Hecht, S. S.; Carmella, S. G.; Yu, N.; Larue, B.; Henry,C.; McIntyre, C.; Claudio, R.; Lechner, J. F.; Stoner, G. D.Anthocyanins in black raspberries prevent esophageal tumors inrats. Cancer Prev. Res. 2009, 2, 84–93.
(45) Shukitt-Hale, B.;Cheng,V.; Joseph, J.A. Effects of blackberries onmotorand cognitive function in aged rats. Nutr. Neurosci. 2009, 12, 135–140.