矢车菊素-3-葡萄糖苷的吸收、代谢及生理功能研究进展
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摘要
矢车菊素-3-葡萄糖苷是自然界中分布最为广泛的一种花青素,因其强抗氧化、抗炎等生理功能而具有潜在促生长、抗腹泻等作用,但其在体内可被迅速代谢,进入血液循环的大部分为其代谢产物。因此,矢车菊素-3-葡萄糖苷的生理功能在很大程度上基于其代谢产物的生理活性。本文就矢车菊素-3-葡萄糖苷在体内的吸收率、吸收部位、主要代谢途径及代谢产物的生理功能进行综述,为其在新型无抗饲料添加剂中的应用提供理论依据。
Cyanoin-3-glucoside( C3 G) is one of the most widely distributed anthocyanins in nature. It has potential biological functions such as growth promotion and anti-diarrhea since its strong anti-oxidant,anti-inflammatory effects. After intake,C3 G can be rapidly metabolized,and the metabolites are the major components that enter circulation. Thus,the biological functions of C3 G are largely based on the bioactivities of its metabolites.This paper reviewed the bioavailability,absorption site,main metabolic pathways of C3 G and the biological functions of its metabolites,to provide theoretical basis for their application in novel feed additives.[Chinese Journal of Animal Nutrition,2019,31( 5) : 2052-2062]
Cyanoin-3-glucoside( C3 G) is one of the most widely distributed anthocyanins in nature. It has potential biological functions such as growth promotion and anti-diarrhea since its strong anti-oxidant,anti-inflammatory effects. After intake,C3 G can be rapidly metabolized,and the metabolites are the major components that enter circulation. Thus,the biological functions of C3 G are largely based on the bioactivities of its metabolites.This paper reviewed the bioavailability,absorption site,main metabolic pathways of C3 G and the biological functions of its metabolites,to provide theoretical basis for their application in novel feed additives.[Chinese Journal of Animal Nutrition,2019,31( 5) : 2052-2062]
引文
[1] WU X L,PRIOR R L. Systematic identification and characterization of anthocyanins by HPLC-ESI-M S/M S in common foods in the United States:fruits and berries[J]. Journal of Agricultural and Food Chemistry,2005,53(7):2589-2599.
[2]杨豆,张卫波,赵倩芸,等.花青素的生物活性及其在饲料上的应用[J].湖南饲料,2016(3):25-27.
[3] MA M M,LI Y,LIU X Y,et al.Cyanidin-3-O-glucoside ameliorates lipopolysaccharide-induced injury both in vivo and in vitro suppression of NF-κB and M APK pathw ays[J]. Inflammation,2015,38(4):1669-1682.
[4] HE Y,HU Y F,JIANG X W,et al.Cyanidin-3-O-glucoside inhibits the UVB-induced ROS/COX-2 pathw ay in HaCaT cells[J].Journal of Photochemistry and Photobiology B:Biology,2017,177:24-31.
[5] WALLACE T C. Anthocyanins in cardiovascular disease[J].Advances in Nutrition,2011,2(1):1-7.
[6] MIN J Y,YU S W,BAEK S H,et al.Neuroprotective effect of cyanidin-3-O-glucoside anthocyanin in mice w ith focal cerebral ischemia[J].Neuroscience Letters,2011,500(3):157-161.
[7] GUO H H,GUO J B,JIANG X W,et al.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[J]. Food and Chemical Toxicology,2012,50(9):3040-3047.
[8] KAY C D,KROON P A,CASSIDY A.The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products[J]. M olecular Nutrition&Food Research,2009,53(S1):S92-S101.
[9] MIYAZAWA T,NAKAGAWA K,KUDO M,et al.Direct intestinal absorption of red fruit anthocyanins,cyanidin-3-glucoside and cyanidin-3,5-diglucoside,into rats and humans[J]. Journal of Agricultural and Food Chemistry,1999,47(3):1083-1091.
[10] ICHIYANAGI T,SHIDA Y,RAHMAN M M,et al.Bioavailability and tissue distribution of anthocyanins in bilberry(Vaccinium myrtillus L.)extract in rats[J]. Journal of Agricultural and Food Chemistry,2006,54(18):6578-6587.
[11] MARCZYLO T H,COOKE D,BROWN K,et al.Pharmacokinetics and metabolism of the putative cancer chemopreventive agent cyanidin-3-glucoside in mice[J]. Cancer Chemotherapy and Pharmacology,2009,64(6):1261-1268.
[12] HANSKE L,ENGST W,LOH G,et al.Contribution of gut bacteria to the metabolism of cyanidin 3-glucoside in human microbiota-associated rats[J]. The British Journal of Nutrition,2013,109(8):1433-1441.
[13] DE FERRARS R M,CZANK C,ZHANG Q,et al.The pharmacokinetics of anthocyanins and their metabolites in humans[J]. British Journal of Pharmacology,2014,171(13):3268-3282.
[14] KAY C D,MAZZA G J,HOLUB B J. Anthocyanins exist in the circulation primarily as metabolites in adult men[J]. The Journal of Nutrition,2005,135(11):2582-2588.
[15] DE FERRARS R M,CASSIDY A,CURTIS P,et al.Phenolic metabolites of anthocyanins follow ing a dietary intervention study in post-menopausal w omen[J].M olecular Nutrition&Food Research,2014,58(3):490-502.
[16] CZANK C,CASSIDY A,ZHANG Q Z,et al.Human metabolism and elimination of the anthocyanin,cyanidin-3-glucoside:a13C-tracer study[J]. The American Journal of Clinical Nutrition,2013,97(5):995-1003.
[17] HASSIMOTTO N M A,GENOVESE M I,LAJOLO F M. Absorption and metabolism of cyanidin-3-glucoside and cyanidin-3-rutinoside extracted from w ild mulberry(Morus nigra L.)in rats[J]. Nutrition Research,2008,28(3):198-207.
[18] FELGINES C,KRISA S,MAURAY A,et al.Radiolabelled cyanidin 3-O-glucoside is poorly absorbed in the mouse[J]. British Journal of Nutrition,2010,103(12):1738-1745.
[19] MILBURY P E,KALT W.Xenobiotic metabolism and berry flavonoid transport across the blood-brain barrier[J]. Journal of Agricultural and Food Chemistry,2010,58(7):3950-3956.
[20] KALT W,BLUMBERG J B,MCDONALD J E,et al.Identification of anthocyanins in the liver,eye,and brain of blueberry-fed pigs[J]. Journal of Agricultural and Food Chemistry,2008,56(3):705-712.
[21] FELGINES C,TEXIER O,GARCIN P,et al. Tissue distribution of anthocyanins in rats fed a blackberry anthocyanin-enriched diet[J]. M olecular Nutrition&Food Research,2009,53(9):1098-1103.
[22] TALAVEERA S,FELGINES C,TEXIER O,et al.Anthocyanins are efficiently absorbed from the stomach in anesthetized rats[J]. The Journal of Nutrition,2003,133(12):4178-4182.
[23] WOODWARD G M,NEEDS P W,KAY C D.Anthocyanin-derived phenolic acids form glucuronides follow ing simulated gastrointestinal digestion and microsomal glucuronidation[J].M olecular Nutrition&Food Research,2011,55(3):378-386.
[24] MILBURY P E,CAO G H,PRIOR R L,et al. Bioavailablility of elderberry anthocyanins[J]. M echanisms of Ageing and Development,2002,123(8):997-1006.
[25] CAI H,THOMASSET S C,BERRY D P,et al.Determination of anthocyanins in the urine of patients w ith colorectal liver metastases after administration of bilberry extract[J]. Biomedical Chromatography,2011,25(6):660-663.
[26] PASSAMONTI S,VRHOVSEK U,VANZO A,et al.The stomach as a site for anthocyanins absorption from food[J]. FEBS Letters,2003,544(1/2/3):210-213.
[27] TALAVERA S,FELGINES C,TEXIER O,et al. Anthocyanin metabolism in rats and their distribution to digestive area,kidney,and brain[J]. Journal of Agricultural and Food Chemistry,2005,53(10):3902-3908.
[28] FANG J. Some anthocyanins could be efficiently absorbed across the gastrointestinal mucosa:extensive Presystemic metabolism reduces apparent bioavailability[J]. Journal of Agricultural and Food Chemistry,2014,62(18):3904-3911.
[29] MATUSCHEK M C,HENDRIKS W H,MCGHIE T K,et al.The jejunum is the main site of absorption for anthocyanins in mice[J]. The Journal of Nutritional Biochemistry,2006,17(1):31-36.
[30] KEPPLER K,HUMPF H U.Metabolism of anthocyanins and their phenolic degradation products by the intestinal microflora[J]. Bioorganic&M edicinal Chemistry,2005,13(17):5195-5205.
[31] TALAVEERA S,FELGINES C,TEXIER O,et al.Anthocyanins are efficiently absorbed from the small intestine in rats[J]. The Journal of Nutrition,2004,134(9):2275-2279.
[32] FELGINES C,TALAVERA S,TEXIER O,et al. Absorption and metabolism of red orange juice anthocyanins in rats[J]. British Journal of Nutrition,2006,95(5):898-904.
[33] ZOU T B,FENG D,SONG G,et al.The role of sodium-dependent glucose transporter 1 and glucose transporter 2 in the absorption of cyanidin-3-O-β-glucoside in Caco-2 cells[J]. Nutrients,2014,6(10):4165-4177.
[34] FELGINES C,TALAVERA S,TEXIER O,et al.Blackberry anthocyanins are mainly recovered from urine as methylated and glucuronidated conjugates in humans[J].Journal of Agricultural and Food Chemistry,2005,53(20):7721-7727.
[35] ICHIYANAGI T,SHIDA Y,RAHMAN M M,et al.M etabolic pathw ay of cyanidin 3-O-β-D-glucopyranoside in rats[J]. Journal of Agricultural and Food Chemistry,2005,53(1):145-150.
[36] ICHIYANAGI T,SHIDA Y,RAHMAN M M,et al.Extended glucuronidation is another major path of cyanidin 3-O-β-D-glucopyranoside metabolism in rats[J]. Journal of Agricultural and Food Chemistry,2005,53(18):7312-7319.
[37] TSUDA T,HORIO F,OSAWA T.Absorption and metabolism of cyanidin 3-O-β-D-glucoside in rats[J].FEBS Letters,1999,449(2/3):179-182.
[38] FLESCHHUT J,KRATZER F,RECHKEMMER G,et al. Stability and biotransformation of various dietary anthocyanins in vitro[J]. European Journal of Nutrition,2006,45(1):7-18.
[39] VITAGLIONE P,DONNARUMMA G,NAPOLITANO A,et al. Protocatechuic acid is the major human metabolite of cyanidin-glucosides[J]. The Journal of Nutrition,2007,137(9):2043-2048.
[40] WU X L,PITTMANⅢH E,PRIOR R L.Pelargonidin is absorbed and metabolized differently than cyanidin after marionberry consumption in pigs[J]. The Journal of Nutrition,2004,134(10):2603-2610.
[41] KALT W,LIU Y,MCDONALD J E,et al.Anthocyanin metabolites are abundant and persistent in human urine[J].Journal of Agricultural and Food Chemistry,2014,62(18):3926-3934.
[42] HIDALGO M,ORUNA-CONCHA M J,KOLIDA S,et al.M etabolism of anthocyanins by human gut microflora and their influence on gut bacterial grow th[J].Journal of Agricultural and Food Chemistry,2012,60(15):3882-3890.
[43] WILLIAMSON G,CLIFFORD M N.Colonic metabolites of berry polyphenols:the missing link to biological activity?[J]. British Journal of Nutrition,2010,104(Suppl.3):S48-S66.
[44] GONZALEZ-BARRIO R,EDWARDS C A. CROZIER A. Colonic catabolism of ellagitannins,ellagic acid,and raspberry anthocyanins:in vivo and in vitro studies[J]. Drug M etabolism and Disposition,2011,39(9):1680-1688.
[45] CASSIDY A,ROGERS G,PETERSON J J,et al.Higher dietary anthocyanin and flavonol intakes are associated w ith anti-inflammatory effects in a population of US adults[J]. The American Journal of Clinical Nutrition,2015,102(1):172-181.
[46] EDIRISINGHE I,BANASZEWSKI K,CAPPOZZO J,et al.Straw berry anthocyanin and its association w ith postprandial inflammation and insulin[J].British Journal of Nutrition,2011,106(6):913-922.
[47] ZHU Y,LING W,GUO H,et al. Anti-inflammatory effect of purified dietary anthocyanin in adults w ith hypercholesterolemia:a randomized controlled trial[J]. Nutrition,Metabolism and Cardiovascular Diseases,2013,23(9):843-849.
[48] RODRIGUEZ-MATEOS A,RENDEIRO C,BERGILLOS-M ECA T,et al. Intake and time dependence of blueberry flavonoid-induced improvements in vascular function:a randomized,controlled,double-blind,crossover intervention study w ith mechanistic insights into biological activity[J].The American Journal of Clinical Nutrition,2013,98(5):1179-1191.
[49] HASSELLUND S S,FLAA A,KJELDSEN S E,et al.Effects of anthocyanins on cardiovascular risk factors and inflammation in pre-hypertensive men:a doubleblind randomized placebo-controlled crossover study[J]. Journal of Human Hypertension,2013,27(2):100-106.
[50] SUN C D,ZHENG Y X,CHEN Q J,et al.Purification and anti-tumour activity of cyanidin-3-O-glucoside from Chinese bayberry fruit[J]. Food Chemistry,2012,131(4):1287-1294.
[51] SHIH P H,YEH C T,YEN G C.Effects of anthocyanidin on the inhibition of proliferation and induction of apoptosis in human gastric adenocarcinoma cells[J].Food and Chemical Toxicology,2005,43(10):1557-1566.
[52] REDDY M K,ALEXANDER-LINDO R L,NAIR M G. Relative inhibition of lipid peroxidation,cyclooxygenase enzymes,and human tumor cell proliferation by natural food colors[J]. Journal of Agricultural and Food Chemistry,2005,53(23):9268-9273.
[53] AMIN H P,CZANK C,RAHEEM S,et al.Anthocyanins and their physiologically relevant metabolites alter the expression of IL-6 and VCAM-1 in CD40L and oxidized LDL challenged vascular endothelial cells[J].M olecular Nutrition&Food Research,2015,59(6):1095-1106.
[54] KRGA I,MONFOULET L E,KONIC-RISTIC A,et al. Anthocyanins and their gut metabolites reduce the adhesion of monocyte to TNFα-activated endothelial cells at physiologically relevant concentrations[J].Archives of Biochemistry and Biophysics,2016,599:51-59.
[55] AMINI A M,SPENCER J P E,YAQOOB P. Effects of pelargonidin-3-O-glucoside and its metabolites on lipopolysaccharide-stimulated cytokine production by THP-1 monocytes and macrophages[J]. Cytokine,2018,103:29-33.
[56] WU S S,YANO S,HISANAGA A,et al.Polyphenols from Lonicera caerulea L.berry attenuate experimental nonalcoholic steatohepatitis by inhibiting proinflammatory cytokines productions and lipid peroxidation[J].M olecular Nutrition&Food Research,2017,61(4):1600858.
[57] MIN S W,RYU S N,KIM D H. Anti-inflammatory effects of black rice,cyanidin-3-O-β-D-glycoside,and its metabolites,cyanidin and protocatechuic acid[J].International Immunopharmacology,2010,10(8):959-966.
[58] SEMAMING Y,PANNENGPETCH P,CHATTIPAKORN S C,et al.Pharmacological properties of protocatechuic acid and its potential roles as complementary medicine[J].Evidence-Based Complementary and Alternative M edicine,2015,2015:593902.
[59] JAYARAMAN P,SAKHARKAR M K,LIM C S,et al. Activity and interactions of antibiotic and phytochemical combinations against Pseudomonas aeruginosa in vitro[J]. International Journal of Biological Sciences,2010,6(6):556-568.
[60] SROKA Z,CISOWSKI W.Hydrogen peroxide scavenging,antioxidant and anti-radical activity of some phenolic acids[J].Food and Chemical Toxicology,2003,41(6):753-758.
[61] SHI G F,AN L J,JIANG B,et al. Alpinia protocatechuic acid protects against oxidative damage in vitro and reduces oxidative stress in vivo[J]. Neuroscience Letters,2006,403(3):206-210.
[62] VARIR,D’ARCHIVIO M,FILESI C,et al.Protocatechuic acid induces antioxidant/detoxifying enzyme expression through JNK-mediated Nrf2 activation in murine macrophages[J]. Journal of Nutritional Biochemistry,2011,22(5):409-417.
[63] BLANCHARD C,POUCHAIN D,VANDERKAM P,et al. Efficacy of phloroglucinol for treatment of abdominal pain:a systematic review of literature and meta-analysis of randomised controlled trials versus placebo[J]. European Journal of Clinical Pharmacology,2018,74(5):541-548.
[64] KIM M M,KIM S K.Effect of phloroglucinol on oxidative stress and inflammation[J].Food and Chemical Toxicology,2010,48(10):2925-2933.
[65] KANG K A,LEE K H,CHAE S,et al.Cytoprotective effect of phloroglucinol on oxidative stress induced cell damage via catalase activation[J].Journal of Cellular Biochemistry,2006,97(3):609-620.
[66] LI N S,LUO X J,ZHANG Y S,et al.Phloroglucinol protects gastric mucosa against ethanol-induced injury through regulating myeloperoxidase and catalase activities[J].Fundamental&Clinical Pharmacology,2011,25(4):462-468.
[67] KIM M C,KIM S J,KIM D S,et al.Vanillic acid inhibits inflammatory mediators by suppressing NF-κB in lipopolysaccharide-stimulated mouse peritoneal macrophages[J]. Immunopharmacology and Immunotoxicology,2011,33(3):525-532.
[68] ANBALAGAN V,RAJU K,SHANMUGAM M. Assessment of lipid peroxidation and antioxidant status in vanillic acid treated 7,12-dimethylbenz[a]anthracene induced hamster buccal pouch carcinogenesis[J].Journal of Clinical and Diagnostic Research,2017,11(3):BF01-BF04.
[69] PRINCE P S M,RAJAKUMAR S,DHANASEKAR K.Protective effects of vanillic acid on electrocardiogram,lipid peroxidation,antioxidants,proinflammatory markers and histopathology in isoproterenol induced cardiotoxic rats[J]. European Journal of Pharmacology,2011,668(1/2):233-240.
[70] KUMAR S,PRAHALATHAN P,SARAVANAKUM AR M,et al. Vanillic acid prevents the deregulation of lipid metabolism,endothelin 1 and up regulation of endothelial nitric oxide synthase in nitric oxide deficient hypertensive rats[J]. European Journal of Pharmacology,2014,743:117-125.
[71] AMIN F U,SHAH S A,KIM M O.Vanillic acid attenuates Aβ1-42-induced oxidative stress and cognitive impairment in mice[J]. Scientific Reports,2017,7:40753.
[72] WOLSZLEGER M,STAN C D,APOTROSOAEI M,et al. New hydrazones of ferulic acid:synthesis,characterization and biological activity[J]. Revista M edico-ChirurgicalA Societtii De M edici爦i Naturali爧ti Din Ia爧i,2014,118(4):1150-1156.
[73] CATINO S,PACIELLO F,MICELI F,et al. Ferulic acid regulates the Nrf2/heme oxygenase-1 system and counteracts trimethyltin-induced neuronal damage in the human neuroblastoma cell line SH-SY5Y[J].Frontiers in Pharmacology,2015,6:305.
[74] ALAM M A,SERNIA C,BROWN L.Ferulic acid improves cardiovascular and kidney structure and function in hypertensive rats[J]. Journal of Cardiovascular Pharmacology,2013,61(3):240-249.
[75] SONG Y,WEN L N,SUN J X,et al. Cytoprotective mechanism of ferulic acid against high glucose-induced oxidative stress in cardiomyocytes and hepatocytes[J].Food&Nutrition Research,2016,60:30323.
[76] YIN J,WU M M,XIAO H,et al.Development of an antioxidant system after early w eaning in piglets[J].Journal of Animal Science,2014,92(2):612-619.
[77] LIU L L,HE J H,XIE H B,et al.Resveratrol induces antioxidant and heat shock protein mRNA expression in response to heat stress in black-boned chickens[J].Poultry Science,2014,93(1):54-62.
[78] HE S S,GUO Y H,ZHAO J X,et al.Ferulic acid protects against heat stress-induced intestinal epithelial barrier dysfunction in IEC-6 cells via the PI3K/Aktmediated Nrf2/HO-1 signaling pathw ay[J]. International Journal of Hyperthermia,2018:1-10,doi:10.1080/02656736.2018.1483534.
[79] HE S S,LIU F H,XU L,et al. Protective effects of Ferulic acid against heat stress-induced intestinal epithelial barrier dysfunction in vitro and in vivo[J].PLoS One,2016,11(2):e0145236.
[80] PEI Y F,YANG L,WU L,et al. Combined effect of apigenin and ferulic acid on frozen-thaw ed boar sperm quality[J]. Animal Science Journal,2018,89(7):956-965.
[81] AFFONSO F J,CARVALHO H F,LANCONI R,et al. Addition of antioxidants myoinositol,ferulic acid,and melatonin and their effects on sperm motility,membrane integrity,and reactive oxygen species production in cooled equine semen[J]. Journal of Equine Veterinary Science,2017,59:57-63.
[82] LI Y J,LI L Y,LI J L,et al.Effects of dietary supplementation w ith ferulic acid or vitamin E individually or in combination on meat quality and antioxidant capacity of finishing pigs[J].Asian-Australasian Journal of Animal Sciences,2015,28(3):374-381.
[83] MACIAS-CRUZ U,VICENTE-PEREZ R,LOPEZBACA M A,et al.Effects of dietary ferulic acid on reproductive function and metabolism of pre-pubertal hairbreed ew es during the anestrous season[J]. Theriogenology,2018,119:220-224.
[84] YU L J,WU F,JIANG M,et al.Ferulic acid:a natural compound as an efficient feed additive for GIFT(Oreochromis niloticus)[J]. Aquaculture Nutrition,2018,24(1):27-35.
[85] VAN DEN BERG T P.Acute infectious bursal disease in poultry:a review[J]. Avian Pathology,2000,29(3):175-194.
[86] OU C B,PANG Q,CHEN X,et al. Protocatechuic acid,a new active substance against the challenge of avian infectious bursal disease virus[J]. Poultry Science,2012,91(7):1604-1609.
[2]杨豆,张卫波,赵倩芸,等.花青素的生物活性及其在饲料上的应用[J].湖南饲料,2016(3):25-27.
[3] MA M M,LI Y,LIU X Y,et al.Cyanidin-3-O-glucoside ameliorates lipopolysaccharide-induced injury both in vivo and in vitro suppression of NF-κB and M APK pathw ays[J]. Inflammation,2015,38(4):1669-1682.
[4] HE Y,HU Y F,JIANG X W,et al.Cyanidin-3-O-glucoside inhibits the UVB-induced ROS/COX-2 pathw ay in HaCaT cells[J].Journal of Photochemistry and Photobiology B:Biology,2017,177:24-31.
[5] WALLACE T C. Anthocyanins in cardiovascular disease[J].Advances in Nutrition,2011,2(1):1-7.
[6] MIN J Y,YU S W,BAEK S H,et al.Neuroprotective effect of cyanidin-3-O-glucoside anthocyanin in mice w ith focal cerebral ischemia[J].Neuroscience Letters,2011,500(3):157-161.
[7] GUO H H,GUO J B,JIANG X W,et al.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[J]. Food and Chemical Toxicology,2012,50(9):3040-3047.
[8] KAY C D,KROON P A,CASSIDY A.The bioactivity of dietary anthocyanins is likely to be mediated by their degradation products[J]. M olecular Nutrition&Food Research,2009,53(S1):S92-S101.
[9] MIYAZAWA T,NAKAGAWA K,KUDO M,et al.Direct intestinal absorption of red fruit anthocyanins,cyanidin-3-glucoside and cyanidin-3,5-diglucoside,into rats and humans[J]. Journal of Agricultural and Food Chemistry,1999,47(3):1083-1091.
[10] ICHIYANAGI T,SHIDA Y,RAHMAN M M,et al.Bioavailability and tissue distribution of anthocyanins in bilberry(Vaccinium myrtillus L.)extract in rats[J]. Journal of Agricultural and Food Chemistry,2006,54(18):6578-6587.
[11] MARCZYLO T H,COOKE D,BROWN K,et al.Pharmacokinetics and metabolism of the putative cancer chemopreventive agent cyanidin-3-glucoside in mice[J]. Cancer Chemotherapy and Pharmacology,2009,64(6):1261-1268.
[12] HANSKE L,ENGST W,LOH G,et al.Contribution of gut bacteria to the metabolism of cyanidin 3-glucoside in human microbiota-associated rats[J]. The British Journal of Nutrition,2013,109(8):1433-1441.
[13] DE FERRARS R M,CZANK C,ZHANG Q,et al.The pharmacokinetics of anthocyanins and their metabolites in humans[J]. British Journal of Pharmacology,2014,171(13):3268-3282.
[14] KAY C D,MAZZA G J,HOLUB B J. Anthocyanins exist in the circulation primarily as metabolites in adult men[J]. The Journal of Nutrition,2005,135(11):2582-2588.
[15] DE FERRARS R M,CASSIDY A,CURTIS P,et al.Phenolic metabolites of anthocyanins follow ing a dietary intervention study in post-menopausal w omen[J].M olecular Nutrition&Food Research,2014,58(3):490-502.
[16] CZANK C,CASSIDY A,ZHANG Q Z,et al.Human metabolism and elimination of the anthocyanin,cyanidin-3-glucoside:a13C-tracer study[J]. The American Journal of Clinical Nutrition,2013,97(5):995-1003.
[17] HASSIMOTTO N M A,GENOVESE M I,LAJOLO F M. Absorption and metabolism of cyanidin-3-glucoside and cyanidin-3-rutinoside extracted from w ild mulberry(Morus nigra L.)in rats[J]. Nutrition Research,2008,28(3):198-207.
[18] FELGINES C,KRISA S,MAURAY A,et al.Radiolabelled cyanidin 3-O-glucoside is poorly absorbed in the mouse[J]. British Journal of Nutrition,2010,103(12):1738-1745.
[19] MILBURY P E,KALT W.Xenobiotic metabolism and berry flavonoid transport across the blood-brain barrier[J]. Journal of Agricultural and Food Chemistry,2010,58(7):3950-3956.
[20] KALT W,BLUMBERG J B,MCDONALD J E,et al.Identification of anthocyanins in the liver,eye,and brain of blueberry-fed pigs[J]. Journal of Agricultural and Food Chemistry,2008,56(3):705-712.
[21] FELGINES C,TEXIER O,GARCIN P,et al. Tissue distribution of anthocyanins in rats fed a blackberry anthocyanin-enriched diet[J]. M olecular Nutrition&Food Research,2009,53(9):1098-1103.
[22] TALAVEERA S,FELGINES C,TEXIER O,et al.Anthocyanins are efficiently absorbed from the stomach in anesthetized rats[J]. The Journal of Nutrition,2003,133(12):4178-4182.
[23] WOODWARD G M,NEEDS P W,KAY C D.Anthocyanin-derived phenolic acids form glucuronides follow ing simulated gastrointestinal digestion and microsomal glucuronidation[J].M olecular Nutrition&Food Research,2011,55(3):378-386.
[24] MILBURY P E,CAO G H,PRIOR R L,et al. Bioavailablility of elderberry anthocyanins[J]. M echanisms of Ageing and Development,2002,123(8):997-1006.
[25] CAI H,THOMASSET S C,BERRY D P,et al.Determination of anthocyanins in the urine of patients w ith colorectal liver metastases after administration of bilberry extract[J]. Biomedical Chromatography,2011,25(6):660-663.
[26] PASSAMONTI S,VRHOVSEK U,VANZO A,et al.The stomach as a site for anthocyanins absorption from food[J]. FEBS Letters,2003,544(1/2/3):210-213.
[27] TALAVERA S,FELGINES C,TEXIER O,et al. Anthocyanin metabolism in rats and their distribution to digestive area,kidney,and brain[J]. Journal of Agricultural and Food Chemistry,2005,53(10):3902-3908.
[28] FANG J. Some anthocyanins could be efficiently absorbed across the gastrointestinal mucosa:extensive Presystemic metabolism reduces apparent bioavailability[J]. Journal of Agricultural and Food Chemistry,2014,62(18):3904-3911.
[29] MATUSCHEK M C,HENDRIKS W H,MCGHIE T K,et al.The jejunum is the main site of absorption for anthocyanins in mice[J]. The Journal of Nutritional Biochemistry,2006,17(1):31-36.
[30] KEPPLER K,HUMPF H U.Metabolism of anthocyanins and their phenolic degradation products by the intestinal microflora[J]. Bioorganic&M edicinal Chemistry,2005,13(17):5195-5205.
[31] TALAVEERA S,FELGINES C,TEXIER O,et al.Anthocyanins are efficiently absorbed from the small intestine in rats[J]. The Journal of Nutrition,2004,134(9):2275-2279.
[32] FELGINES C,TALAVERA S,TEXIER O,et al. Absorption and metabolism of red orange juice anthocyanins in rats[J]. British Journal of Nutrition,2006,95(5):898-904.
[33] ZOU T B,FENG D,SONG G,et al.The role of sodium-dependent glucose transporter 1 and glucose transporter 2 in the absorption of cyanidin-3-O-β-glucoside in Caco-2 cells[J]. Nutrients,2014,6(10):4165-4177.
[34] FELGINES C,TALAVERA S,TEXIER O,et al.Blackberry anthocyanins are mainly recovered from urine as methylated and glucuronidated conjugates in humans[J].Journal of Agricultural and Food Chemistry,2005,53(20):7721-7727.
[35] ICHIYANAGI T,SHIDA Y,RAHMAN M M,et al.M etabolic pathw ay of cyanidin 3-O-β-D-glucopyranoside in rats[J]. Journal of Agricultural and Food Chemistry,2005,53(1):145-150.
[36] ICHIYANAGI T,SHIDA Y,RAHMAN M M,et al.Extended glucuronidation is another major path of cyanidin 3-O-β-D-glucopyranoside metabolism in rats[J]. Journal of Agricultural and Food Chemistry,2005,53(18):7312-7319.
[37] TSUDA T,HORIO F,OSAWA T.Absorption and metabolism of cyanidin 3-O-β-D-glucoside in rats[J].FEBS Letters,1999,449(2/3):179-182.
[38] FLESCHHUT J,KRATZER F,RECHKEMMER G,et al. Stability and biotransformation of various dietary anthocyanins in vitro[J]. European Journal of Nutrition,2006,45(1):7-18.
[39] VITAGLIONE P,DONNARUMMA G,NAPOLITANO A,et al. Protocatechuic acid is the major human metabolite of cyanidin-glucosides[J]. The Journal of Nutrition,2007,137(9):2043-2048.
[40] WU X L,PITTMANⅢH E,PRIOR R L.Pelargonidin is absorbed and metabolized differently than cyanidin after marionberry consumption in pigs[J]. The Journal of Nutrition,2004,134(10):2603-2610.
[41] KALT W,LIU Y,MCDONALD J E,et al.Anthocyanin metabolites are abundant and persistent in human urine[J].Journal of Agricultural and Food Chemistry,2014,62(18):3926-3934.
[42] HIDALGO M,ORUNA-CONCHA M J,KOLIDA S,et al.M etabolism of anthocyanins by human gut microflora and their influence on gut bacterial grow th[J].Journal of Agricultural and Food Chemistry,2012,60(15):3882-3890.
[43] WILLIAMSON G,CLIFFORD M N.Colonic metabolites of berry polyphenols:the missing link to biological activity?[J]. British Journal of Nutrition,2010,104(Suppl.3):S48-S66.
[44] GONZALEZ-BARRIO R,EDWARDS C A. CROZIER A. Colonic catabolism of ellagitannins,ellagic acid,and raspberry anthocyanins:in vivo and in vitro studies[J]. Drug M etabolism and Disposition,2011,39(9):1680-1688.
[45] CASSIDY A,ROGERS G,PETERSON J J,et al.Higher dietary anthocyanin and flavonol intakes are associated w ith anti-inflammatory effects in a population of US adults[J]. The American Journal of Clinical Nutrition,2015,102(1):172-181.
[46] EDIRISINGHE I,BANASZEWSKI K,CAPPOZZO J,et al.Straw berry anthocyanin and its association w ith postprandial inflammation and insulin[J].British Journal of Nutrition,2011,106(6):913-922.
[47] ZHU Y,LING W,GUO H,et al. Anti-inflammatory effect of purified dietary anthocyanin in adults w ith hypercholesterolemia:a randomized controlled trial[J]. Nutrition,Metabolism and Cardiovascular Diseases,2013,23(9):843-849.
[48] RODRIGUEZ-MATEOS A,RENDEIRO C,BERGILLOS-M ECA T,et al. Intake and time dependence of blueberry flavonoid-induced improvements in vascular function:a randomized,controlled,double-blind,crossover intervention study w ith mechanistic insights into biological activity[J].The American Journal of Clinical Nutrition,2013,98(5):1179-1191.
[49] HASSELLUND S S,FLAA A,KJELDSEN S E,et al.Effects of anthocyanins on cardiovascular risk factors and inflammation in pre-hypertensive men:a doubleblind randomized placebo-controlled crossover study[J]. Journal of Human Hypertension,2013,27(2):100-106.
[50] SUN C D,ZHENG Y X,CHEN Q J,et al.Purification and anti-tumour activity of cyanidin-3-O-glucoside from Chinese bayberry fruit[J]. Food Chemistry,2012,131(4):1287-1294.
[51] SHIH P H,YEH C T,YEN G C.Effects of anthocyanidin on the inhibition of proliferation and induction of apoptosis in human gastric adenocarcinoma cells[J].Food and Chemical Toxicology,2005,43(10):1557-1566.
[52] REDDY M K,ALEXANDER-LINDO R L,NAIR M G. Relative inhibition of lipid peroxidation,cyclooxygenase enzymes,and human tumor cell proliferation by natural food colors[J]. Journal of Agricultural and Food Chemistry,2005,53(23):9268-9273.
[53] AMIN H P,CZANK C,RAHEEM S,et al.Anthocyanins and their physiologically relevant metabolites alter the expression of IL-6 and VCAM-1 in CD40L and oxidized LDL challenged vascular endothelial cells[J].M olecular Nutrition&Food Research,2015,59(6):1095-1106.
[54] KRGA I,MONFOULET L E,KONIC-RISTIC A,et al. Anthocyanins and their gut metabolites reduce the adhesion of monocyte to TNFα-activated endothelial cells at physiologically relevant concentrations[J].Archives of Biochemistry and Biophysics,2016,599:51-59.
[55] AMINI A M,SPENCER J P E,YAQOOB P. Effects of pelargonidin-3-O-glucoside and its metabolites on lipopolysaccharide-stimulated cytokine production by THP-1 monocytes and macrophages[J]. Cytokine,2018,103:29-33.
[56] WU S S,YANO S,HISANAGA A,et al.Polyphenols from Lonicera caerulea L.berry attenuate experimental nonalcoholic steatohepatitis by inhibiting proinflammatory cytokines productions and lipid peroxidation[J].M olecular Nutrition&Food Research,2017,61(4):1600858.
[57] MIN S W,RYU S N,KIM D H. Anti-inflammatory effects of black rice,cyanidin-3-O-β-D-glycoside,and its metabolites,cyanidin and protocatechuic acid[J].International Immunopharmacology,2010,10(8):959-966.
[58] SEMAMING Y,PANNENGPETCH P,CHATTIPAKORN S C,et al.Pharmacological properties of protocatechuic acid and its potential roles as complementary medicine[J].Evidence-Based Complementary and Alternative M edicine,2015,2015:593902.
[59] JAYARAMAN P,SAKHARKAR M K,LIM C S,et al. Activity and interactions of antibiotic and phytochemical combinations against Pseudomonas aeruginosa in vitro[J]. International Journal of Biological Sciences,2010,6(6):556-568.
[60] SROKA Z,CISOWSKI W.Hydrogen peroxide scavenging,antioxidant and anti-radical activity of some phenolic acids[J].Food and Chemical Toxicology,2003,41(6):753-758.
[61] SHI G F,AN L J,JIANG B,et al. Alpinia protocatechuic acid protects against oxidative damage in vitro and reduces oxidative stress in vivo[J]. Neuroscience Letters,2006,403(3):206-210.
[62] VARIR,D’ARCHIVIO M,FILESI C,et al.Protocatechuic acid induces antioxidant/detoxifying enzyme expression through JNK-mediated Nrf2 activation in murine macrophages[J]. Journal of Nutritional Biochemistry,2011,22(5):409-417.
[63] BLANCHARD C,POUCHAIN D,VANDERKAM P,et al. Efficacy of phloroglucinol for treatment of abdominal pain:a systematic review of literature and meta-analysis of randomised controlled trials versus placebo[J]. European Journal of Clinical Pharmacology,2018,74(5):541-548.
[64] KIM M M,KIM S K.Effect of phloroglucinol on oxidative stress and inflammation[J].Food and Chemical Toxicology,2010,48(10):2925-2933.
[65] KANG K A,LEE K H,CHAE S,et al.Cytoprotective effect of phloroglucinol on oxidative stress induced cell damage via catalase activation[J].Journal of Cellular Biochemistry,2006,97(3):609-620.
[66] LI N S,LUO X J,ZHANG Y S,et al.Phloroglucinol protects gastric mucosa against ethanol-induced injury through regulating myeloperoxidase and catalase activities[J].Fundamental&Clinical Pharmacology,2011,25(4):462-468.
[67] KIM M C,KIM S J,KIM D S,et al.Vanillic acid inhibits inflammatory mediators by suppressing NF-κB in lipopolysaccharide-stimulated mouse peritoneal macrophages[J]. Immunopharmacology and Immunotoxicology,2011,33(3):525-532.
[68] ANBALAGAN V,RAJU K,SHANMUGAM M. Assessment of lipid peroxidation and antioxidant status in vanillic acid treated 7,12-dimethylbenz[a]anthracene induced hamster buccal pouch carcinogenesis[J].Journal of Clinical and Diagnostic Research,2017,11(3):BF01-BF04.
[69] PRINCE P S M,RAJAKUMAR S,DHANASEKAR K.Protective effects of vanillic acid on electrocardiogram,lipid peroxidation,antioxidants,proinflammatory markers and histopathology in isoproterenol induced cardiotoxic rats[J]. European Journal of Pharmacology,2011,668(1/2):233-240.
[70] KUMAR S,PRAHALATHAN P,SARAVANAKUM AR M,et al. Vanillic acid prevents the deregulation of lipid metabolism,endothelin 1 and up regulation of endothelial nitric oxide synthase in nitric oxide deficient hypertensive rats[J]. European Journal of Pharmacology,2014,743:117-125.
[71] AMIN F U,SHAH S A,KIM M O.Vanillic acid attenuates Aβ1-42-induced oxidative stress and cognitive impairment in mice[J]. Scientific Reports,2017,7:40753.
[72] WOLSZLEGER M,STAN C D,APOTROSOAEI M,et al. New hydrazones of ferulic acid:synthesis,characterization and biological activity[J]. Revista M edico-ChirurgicalA Societtii De M edici爦i Naturali爧ti Din Ia爧i,2014,118(4):1150-1156.
[73] CATINO S,PACIELLO F,MICELI F,et al. Ferulic acid regulates the Nrf2/heme oxygenase-1 system and counteracts trimethyltin-induced neuronal damage in the human neuroblastoma cell line SH-SY5Y[J].Frontiers in Pharmacology,2015,6:305.
[74] ALAM M A,SERNIA C,BROWN L.Ferulic acid improves cardiovascular and kidney structure and function in hypertensive rats[J]. Journal of Cardiovascular Pharmacology,2013,61(3):240-249.
[75] SONG Y,WEN L N,SUN J X,et al. Cytoprotective mechanism of ferulic acid against high glucose-induced oxidative stress in cardiomyocytes and hepatocytes[J].Food&Nutrition Research,2016,60:30323.
[76] YIN J,WU M M,XIAO H,et al.Development of an antioxidant system after early w eaning in piglets[J].Journal of Animal Science,2014,92(2):612-619.
[77] LIU L L,HE J H,XIE H B,et al.Resveratrol induces antioxidant and heat shock protein mRNA expression in response to heat stress in black-boned chickens[J].Poultry Science,2014,93(1):54-62.
[78] HE S S,GUO Y H,ZHAO J X,et al.Ferulic acid protects against heat stress-induced intestinal epithelial barrier dysfunction in IEC-6 cells via the PI3K/Aktmediated Nrf2/HO-1 signaling pathw ay[J]. International Journal of Hyperthermia,2018:1-10,doi:10.1080/02656736.2018.1483534.
[79] HE S S,LIU F H,XU L,et al. Protective effects of Ferulic acid against heat stress-induced intestinal epithelial barrier dysfunction in vitro and in vivo[J].PLoS One,2016,11(2):e0145236.
[80] PEI Y F,YANG L,WU L,et al. Combined effect of apigenin and ferulic acid on frozen-thaw ed boar sperm quality[J]. Animal Science Journal,2018,89(7):956-965.
[81] AFFONSO F J,CARVALHO H F,LANCONI R,et al. Addition of antioxidants myoinositol,ferulic acid,and melatonin and their effects on sperm motility,membrane integrity,and reactive oxygen species production in cooled equine semen[J]. Journal of Equine Veterinary Science,2017,59:57-63.
[82] LI Y J,LI L Y,LI J L,et al.Effects of dietary supplementation w ith ferulic acid or vitamin E individually or in combination on meat quality and antioxidant capacity of finishing pigs[J].Asian-Australasian Journal of Animal Sciences,2015,28(3):374-381.
[83] MACIAS-CRUZ U,VICENTE-PEREZ R,LOPEZBACA M A,et al.Effects of dietary ferulic acid on reproductive function and metabolism of pre-pubertal hairbreed ew es during the anestrous season[J]. Theriogenology,2018,119:220-224.
[84] YU L J,WU F,JIANG M,et al.Ferulic acid:a natural compound as an efficient feed additive for GIFT(Oreochromis niloticus)[J]. Aquaculture Nutrition,2018,24(1):27-35.
[85] VAN DEN BERG T P.Acute infectious bursal disease in poultry:a review[J]. Avian Pathology,2000,29(3):175-194.
[86] OU C B,PANG Q,CHEN X,et al. Protocatechuic acid,a new active substance against the challenge of avian infectious bursal disease virus[J]. Poultry Science,2012,91(7):1604-1609.