The Role of Anthocyanins in Drug Discovery: Recent Developments

Author(s): Marco Bonesi*, Mariarosaria Leporini, Maria C. Tenuta, Rosa Tundis

Journal Name: Current Drug Discovery Technologies

Volume 17 , Issue 3 , 2020

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Graphical Abstract:


Abstract:

Natural compounds have always played a key role in drug discovery. Anthocyanins are secondary metabolites belonging to the flavonoids family responsible for the purple, blue, and red colour of many vegetables and fruits. These phytochemicals have attracted the interest of researchers for their important implications in human health and for their use as natural colorants. Many in vitro and in vivo studies demonstrated the potential effects of anthocyanins and anthocyanins-rich foods in the prevention and/or treatment of diabetes, cancer, and cardiovascular and neurodegenerative diseases. This review reports the recent literature data and focuses on the potential role of anthocyanins in drug discovery. Their biological activity, analysis of structure-activity relationships, bioavailability, metabolism, and future prospects of their uses are critically described.

Keywords: Anthocyanins, bioactivities, bioavailability, drug discovery, future prospects, ferulic acid.

[1]
He K, Li X, Chen X, et al. Evaluation of antidiabetic potential of selected traditional Chinese medicines in STZ-induced diabetic mice. J Ethnopharmacol 2011; 137(3): 1135-42.
[http://dx.doi.org/10.1016/j.jep.2011.07.033] [PMID: 21798327]
[2]
Clifford MN. Anthocyanins-nature, occurrence and dietary burden. J Sci Food Agric 2000; 80: 1063-72.
[http://dx.doi.org/10.1002/(SICI)1097-0010(20000515)80:7<1063:AID-JSFA605>3.0.CO;2-Q]
[3]
Brouillard R, Dangles O. Flavonoids and flower colour.The flavonoids advances in research since 1986 London: Chapman& Hall 1993.
[http://dx.doi.org/10.1007/978-1-4899-2911-2_13]
[4]
Rivas-Gonzalo JC. Analysis of anthocyanins methods in polyphenol analysis. Cambridge: The Royal Society of Chemistry 2003.
[5]
Galvano F, La Fauci L, Lazzarino G, et al. Cyanidins: metabolism and biological properties. J Nutr Biochem 2004; 15(1): 2-11.
[http://dx.doi.org/10.1016/j.jnutbio.2003.07.004] [PMID: 14711454]
[6]
Chun OK, Chung SJ, Song WO. Estimated dietary flavonoid intake and major food sources of U.S. adults. J Nutr 2007; 137(5): 1244-52.
[http://dx.doi.org/10.1093/jn/137.5.1244] [PMID: 17449588]
[7]
Wu X, Beecher GR, Holden JM, Haytowitz DB, Gebhardt SE, Prior RL. Concentrations of anthocyanins in common foods in the United States and estimation of normal consumption. J Agric Food Chem 2006; 54(11): 4069-75.
[http://dx.doi.org/10.1021/jf060300l] [PMID: 16719536]
[8]
Manach C, Williamson G, Morand C, Scalbert A, Rémésy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 2005; 81(1)(Suppl.): 230S-42S.
[http://dx.doi.org/10.1093/ajcn/81.1.230S] [PMID: 15640486]
[9]
Matsumoto H, Inaba H, Kishi M, Tominaga S, Hirayama M, Tsuda T. Orally administered delphinidin 3-rutinoside and cyanidin 3-rutinoside are directly absorbed in rats and humans and appear in the blood as the intact forms. J Agric Food Chem 2001; 49(3): 1546-51.
[http://dx.doi.org/10.1021/jf001246q] [PMID: 11312894]
[10]
Cao G, Muccitelli HU, Sánchez-Moreno C, Prior RL. Anthocyanins are absorbed in glycated forms in elderly women: a pharmacokinetic study. Am J Clin Nutr 2001; 73(5): 920-6.
[http://dx.doi.org/10.1093/ajcn/73.5.920] [PMID: 11333846]
[11]
Nielsen ILF, Dragsted LO, Ravn-Haren G, Freese R, Rasmussen SE. Absorption and excretion of black currant anthocyanins in humans and watanabe heritable hyperlipidemic rabbits. J Agric Food Chem 2003; 51(9): 2813-20.
[http://dx.doi.org/10.1021/jf025947u] [PMID: 12696978]
[12]
Mazza G, Kay CD, Cottrell T, Holub BJ. Absorption of anthocyanins from blueberries and serum antioxidant status in human subjects. J Agric Food Chem 2002; 50(26): 7731-7.
[http://dx.doi.org/10.1021/jf020690l] [PMID: 12475297]
[13]
Felgines C, Talavera S, Texier O, Gil-Izquierdo A, Lamaison JL, Remesy C. Blackberry anthocyanins are mainly recovered from urine as methylated and glucuronidated conjugates in humans. J Agric Food Chem 2005; 53(20): 7721-7.
[http://dx.doi.org/10.1021/jf051092k] [PMID: 16190623]
[14]
Frank T, Sonntag S, Strass G, Bitsch I, Bitsch R, Netzel M. Urinary pharmacokinetics of cyanidin glycosides in healthy young men following consumption of elderberry juice. Int J Clin Pharmacol Res 2005; 25(2): 47-56.
[PMID: 16060394]
[15]
Felgines C, Talavéra S, Gonthier MP, et al. Strawberry anthocyanins are recovered in urine as glucuro- and sulfoconjugates in humans. J Nutr 2003; 133(5): 1296-301.
[http://dx.doi.org/10.1093/jn/133.5.1296] [PMID: 12730413]
[16]
Lapidot T, Harel S, Granit R. Bioavailability of red wine anthocyanins as detected in human urine. J Agric Food Chem 1998; 47: 67-70.
[http://dx.doi.org/10.1021/jf980704g] [PMID: 10563851]
[17]
Bub A, Watzl B, Heeb D, Rechkemmer G, Briviba K. Malvidin-3-glucoside bioavailability in humans after ingestion of red wine, dealcoholized red wine and red grape juice. Eur J Nutr 2001; 40(3): 113-20.
[http://dx.doi.org/10.1007/s003940170011] [PMID: 11697443]
[18]
Bitsch R, Netzel M, Frank T, Strass G, Bitsch I. Bioavailability and biokinetics of anthocyanins from red grape juice and red wine. J Biomed Biotechnol 2004; 2004(5): 293-8.
[http://dx.doi.org/10.1155/S1110724304403106] [PMID: 15577192]
[19]
Mülleder U, Murkovic M, Pfannhauser W. Urinary excretion of cyanidin glycosides. J Biochem Biophys Methods 2002; 53(1-3): 61-6.
[http://dx.doi.org/10.1016/S0165-022X(02)00093-3] [PMID: 12406587]
[20]
McGhie TK, Ainge GD, Barnett LE, Cooney JM, Jensen DJ. Anthocyanin glycosides from berry fruit are absorbed and excreted unmetabolized by both humans and rats. J Agric Food Chem 2003; 51(16): 4539-48.
[http://dx.doi.org/10.1021/jf026206w] [PMID: 14705874]
[21]
Kurilich AC, Clevidence BA, Britz SJ, Simon PW, Novotny JA. Plasma and urine responses are lower for acylated vs nonacylated anthocyanins from raw and cooked purple carrots. J Agric Food Chem 2005; 53(16): 6537-42.
[http://dx.doi.org/10.1021/jf050570o] [PMID: 16076146]
[22]
Wu X, Cao G, Prior RL. Absorption and metabolism of anthocyanins in elderly women after consumption of elderberry or blueberry. J Nutr 2002; 132(7): 1865-71.
[http://dx.doi.org/10.1093/jn/132.7.1865] [PMID: 12097661]
[23]
Kay CD, Mazza G, Holub BJ, Wang J. Anthocyanin metabolites in human urine and serum. Br J Nutr 2004; 91(6): 933-42.
[http://dx.doi.org/10.1079/BJN20041126] [PMID: 15228048]
[24]
Aura AM, Martin-Lopez P, O’Leary KA, et al. In vitro metabolism of anthocyanins by human gut microflora. Eur J Nutr 2005; 44(3): 133-42.
[http://dx.doi.org/10.1007/s00394-004-0502-2] [PMID: 15309431]
[25]
Keppler K, Humpf HU. Metabolism of anthocyanins and their phenolic degradation products by the intestinal microflora. Bioorg Med Chem 2005; 13(17): 5195-205.
[http://dx.doi.org/10.1016/j.bmc.2005.05.003] [PMID: 15963727]
[26]
Fleschhut J, Kratzer F, Rechkemmer G, Kulling SE. Stability and biotransformation of various dietary anthocyanins in vitro. Eur J Nutr 2006; 45(1): 7-18.
[http://dx.doi.org/10.1007/s00394-005-0557-8] [PMID: 15834757]
[27]
El Mohsen MA, Marks J, Kuhnle G, et al. Absorption, tissue distribution and excretion of pelargonidin and its metabolites following oral administration to rats. Br J Nutr 2006; 95(1): 51-8.
[http://dx.doi.org/10.1079/BJN20051596] [PMID: 16441916]
[28]
Noda Y, Kneyuki T, Igarashi K, Mori A, Packer L. Antioxidant activity of nasunin, an anthocyanin in eggplant peels. Toxicology 2000; 148(2-3): 119-23.
[http://dx.doi.org/10.1016/S0300-483X(00)00202-X] [PMID: 10962130]
[29]
Bąkowska-Barczak A. Acylated anthocyanins as stable, natural food colorants-a review. Pol J Food Sci 2005; 14: 107-16.
[30]
Sarma AD, Sreelakshimi Y, Sharma R. Antioxidant ability of anthocyanins against ascorbic acid oxydation. Phytochemistry 1997; 45: 671-4.
[http://dx.doi.org/10.1016/S0031-9422(97)00057-5]
[31]
Muselík J, García-Alonso M, Martín-López MP, Žemlička M, Rivas-Gonzalo JC. Measurement of antioxidant activity of wine catechins, procyanidins, anthocyanins and pyranoanthocyanins. Int J Mol Sci 2007; 8: 797-809.
[http://dx.doi.org/10.3390/i8080797]
[32]
Kähkönen MP, Heinonen M. Antioxidant activity of anthocyanins and their aglycons. J Agric Food Chem 2003; 51(3): 628-33.
[http://dx.doi.org/10.1021/jf025551i] [PMID: 12537433]
[33]
Tsuda T, Shiga K, Ohshima K, Kawakishi S, Osawa T. Inhibition of lipid peroxidation and the active oxygen radical scavenging effect of anthocyanin pigments isolated from Phaseolus vulgaris L. Biochem Pharmacol 1996; 52(7): 1033-9.
[http://dx.doi.org/10.1016/0006-2952(96)00421-2] [PMID: 8831722]
[34]
Stintzing FC, Stintzing AS, Carle R, Frei B, Wrolstad RE. Color and antioxidant properties of cyanidin-based anthocyanin pigments. J Agric Food Chem 2002; 50(21): 6172-81.
[http://dx.doi.org/10.1021/jf0204811] [PMID: 12358498]
[35]
Wang H, Cao G, Prior RL. Oxygen radical absorbing capacity of anthocyanins. J Agric Food Chem 1997; 45: 304-9.
[http://dx.doi.org/10.1021/jf960421t]
[36]
Terahara N, Callebaut A, Ohba R, Nagata T, Ohnishi-Kameyama M, Suzuki M. Acylated anthocyanidin 3-sophoroside-5-glucosides from Ajuga reptans flowers and the corresponding cell cultures. Phytochemistry 2001; 58(3): 493-500.
[http://dx.doi.org/10.1016/S0031-9422(01)00172-8] [PMID: 11557083]
[37]
Tamura H, Yamagami A. Antioxidative activity ofmonoacylated anthocyanins isolated from Muscat Bailey A grape. J Agric Food Chem 1994; 42: 1612-5.
[http://dx.doi.org/10.1021/jf00044a005]
[38]
Lapidot T, Harel S, Akiri B, Granit R, Kanner J. PH-dependent forms of red wine anthocyanins as antioxidants. J Agric Food Chem 1999; 47(1): 67-70.
[http://dx.doi.org/10.1021/jf980704g] [PMID: 10563851]
[39]
Fernandes I, Marques F, de Freitas V, Mateus N. Antioxidant and antiproliferative properties of methylated metabolites of anthocyanins. Food Chem 2013; 141(3): 2923-33.
[http://dx.doi.org/10.1016/j.foodchem.2013.05.033] [PMID: 23871042]
[41]
Tundis R, Bonesi M, Sicari V, et al. Poncirus trifoliata (L.) Raf.: Chemical composition, antioxidant properties and hypoglycaemic activity via the inhibition of α-amylase and α-glucosidase enzymes. J Funct Foods 2016; 25: 477-85.
[http://dx.doi.org/10.1016/j.jff.2016.06.034]
[42]
Gowd V, Jia Z, Chen W. Anthocyanins as promising molecules and dietary bioactive components against diabetes - A review of recent advances. Trends Food Sci Technol 2017; 68: 1-13.
[http://dx.doi.org/10.1016/j.tifs.2017.07.015]
[43]
Guo X, Yang B, Tan J, Jiang J, Li D. Associations of dietary intakes of anthocyanins and berry fruits with risk of type 2 diabetes mellitus: a systematic review and meta-analysis of prospective cohort studies. Eur J Clin Nutr 2016; 70(12): 1360-7.
[http://dx.doi.org/10.1038/ejcn.2016.142] [PMID: 27530472]
[44]
Soriano Sancho RA, Pastore GM. Evaluation of the effects of anthocyanins in Type 2 Diabetes. Food Res Int 2012; 46: 378-86.
[http://dx.doi.org/10.1016/j.foodres.2011.11.021]
[45]
Kato M, Tani T, Terahara N, Tsuda T. The anthocyanin delphinidin 3-rutinoside stimulates glucagon-like peptide-1 secretion in murine GLUTAG cell line via the Ca2+/calmodulin-dependent kinase II pathway. PLoS One 2015; 10(5)e0126157
[http://dx.doi.org/10.1371/journal.pone.0126157] [PMID: 25962102]
[46]
Tani T, Nishikawa S, Kato M, Tsuda T. Delphinidin 3-rutinoside-rich blackcurrant extract ameliorates glucose tolerance by increasing the release of glucagon-like peptide-1 secretion. Food Sci Nutr 2017; 5(4): 929-33.
[http://dx.doi.org/10.1002/fsn3.478] [PMID: 28748082]
[47]
Yang L, Ling W, Yang Y, et al. Role of purified anthocyanins in improving cardiometabolic risk factors in chinese men and women with prediabetes or early untreated diabetes- A randomized controlled trial. Nutrients 2017; 9(10): 1104.
[http://dx.doi.org/10.3390/nu9101104] [PMID: 28994705]
[48]
Ruderman NB, Carling D, Prentki M, Cacicedo JM. AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest 2013; 123(7): 2764-72.
[http://dx.doi.org/10.1172/JCI67227] [PMID: 23863634]
[49]
Guo H, Ling W. The update of anthocyanins on obesity and type 2 diabetes: experimental evidence and clinical perspectives. Rev Endocr Metab Disord 2015; 16(1): 1-13.
[http://dx.doi.org/10.1007/s11154-014-9302-z] [PMID: 25557610]
[50]
Guo H, Guo J, Jiang X, Li Z, Ling W. 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 2012; 50(9): 3040-7.
[http://dx.doi.org/10.1016/j.fct.2012.06.015] [PMID: 22721980]
[51]
Yan F, Dai G, Zheng X. Mulberry anthocyanin extract ameliorates insulin resistance by regulating PI3K/AKT pathway in HepG2 cells and db/db mice. J Nutr Biochem 2016; 36: 68-80.
[http://dx.doi.org/10.1016/j.jnutbio.2016.07.004] [PMID: 27580020]
[52]
Nizamutdinova IT, Jin YC, Chung JI, et al. The anti-diabetic effect of anthocyanins in streptozotocin-induced diabetic rats through glucose transporter 4 regulation and prevention of insulin resistance and pancreatic apoptosis. Mol Nutr Food Res 2009; 53(11): 1419-29.
[http://dx.doi.org/10.1002/mnfr.200800526] [PMID: 19785000]
[53]
Sasaki R, Nishimura N, Hoshino H, et al. Cyanidin 3-glucoside ameliorates hyperglycemia and insulin sensitivity due to downregulation of retinol binding protein 4 expression in diabetic mice. Biochem Pharmacol 2007; 74(11): 1619-27.
[http://dx.doi.org/10.1016/j.bcp.2007.08.008] [PMID: 17869225]
[54]
Kurimoto Y, Shibayama Y, Inoue S, et al. Black soybean seed coat extract ameliorates hyperglycemia and insulin sensitivity via the activation of AMP-activated protein kinase in diabetic mice. J Agric Food Chem 2013; 61(23): 5558-64.
[http://dx.doi.org/10.1021/jf401190y] [PMID: 23683106]
[55]
Matsukawa T, Inaguma T, Han J, Villareal MO, Isoda H. Cyanidin-3-glucoside derived from black soybeans ameliorate type 2 diabetes through the induction of differentiation of preadipocytes into smaller and insulin-sensitive adipocytes. J Nutr Biochem 2015; 26(8): 860-7.
[http://dx.doi.org/10.1016/j.jnutbio.2015.03.006] [PMID: 25940979]
[56]
Różańska D, Regulska-Ilow B. The significance of anthocyanins in the prevention and treatment of type 2 diabetes. Adv Clin Exp Med 2018; 27(1): 135-42.
[http://dx.doi.org/10.17219/acem/64983] [PMID: 29521054]
[57]
You Y, Han X, Guo J, et al. Cyanidin-3-glucoside attenuates high-fat and high-fructose diet-induced obesity by promoting the thermogenic capacity of brown adipose tissue. J Funct Foods 2018; 41: 62-71.
[http://dx.doi.org/10.1016/j.jff.2017.12.025]
[58]
Rojo LE, Ribnicky D, Logendra S, et al. In vitro and in vivo anti-diabetic effects of anthocyanins from maqui berry (Aristotelia chilensis). Food Chem 2012; 131(2): 387-96.
[http://dx.doi.org/10.1016/j.foodchem.2011.08.066] [PMID: 26279603]
[59]
Chen YF, Shibu MA, Fan MJ, et al. Purple rice anthocyanin extract protects cardiac function in STZ-induced diabetes rat hearts by inhibiting cardiac hypertrophy and fibrosis. J Nutr Biochem 2016; 31: 98-105.
[http://dx.doi.org/10.1016/j.jnutbio.2015.12.020] [PMID: 27133428]
[60]
Adisakwattana S, Yibchok-Anun S, Charoenlertkul P, Wongsasiripat N. Cyanidin-3-rutinoside alleviates postprandial hyperglycemia and its synergism with acarbose by inhibition of intestinal α-glucosidase. J Clin Biochem Nutr 2011; 49(1): 36-41.
[http://dx.doi.org/10.3164/jcbn.10-116] [PMID: 21765605]
[61]
Mojica L, Berhow M, Gonzalez de Mejia E. Black bean anthocyanin-rich extracts as food colorants: Physicochemical stability and antidiabetes potential. Food Chem 2017; 229: 628-39.
[http://dx.doi.org/10.1016/j.foodchem.2017.02.124] [PMID: 28372224]
[62]
Ho GTT, Kase ET, Wangensteen H, Barsett H. Phenolic elderberry extracts, anthocyanins, procyanidins, and metabolites influence glucose and fatty acid uptake in human skeletal muscle Cells. J Agric Food Chem 2017; 65(13): 2677-85.
[http://dx.doi.org/10.1021/acs.jafc.6b05582] [PMID: 28303711]
[63]
Jayaprakasam B, Vareed SK, Olson LK, Nair MG. Insulin secretion by bioactive anthocyanins and anthocyanidins present in fruits. J Agric Food Chem 2005; 53(1): 28-31.
[http://dx.doi.org/10.1021/jf049018+] [PMID: 15631504]
[64]
Loizzo MR, Leporini M, Sicari V, Falco T, Pellicanò MT, Tundis R. Investigating the in vitro hypoglycaemic and antioxidant properties of Citrus × clementina Hort. juice. Eur Food Res Technol 2018; 244: 523-34.
[http://dx.doi.org/10.1007/s00217-017-2978-z]
[65]
McDougall GJ, Stewart D. The inhibitory effects of berry polyphenols on digestive enzymes. Biofactors 2005; 23(4): 189-95.
[http://dx.doi.org/10.1002/biof.5520230403] [PMID: 16498205]
[66]
Adisakwattana S, Charoenlertkul P, Yibchok-Anun S. α-Glucosidase inhibitory activity of cyanidin-3-galactoside and synergistic effect with acarbose. J Enzyme Inhib Med Chem 2009; 24(1): 65-9.
[http://dx.doi.org/10.1080/14756360801906947] [PMID: 18615280]
[67]
Worsztynowicz P, Napierała M, Białas W, Grajek W, Olkowicza M. Pancreatic α-amylase and lipase inhibitory activity of polyphenol compounds present in the extract of black chokeberry (Aronia melanocarpa L.). Process Biochem 2014; 49: 1457-63.
[http://dx.doi.org/10.1016/j.procbio.2014.06.002]
[68]
Kirakosyan A, Gutierrez E, Ramos Solano B, Seymour EM, Bolling SF. The inhibitory potential of Montmorency tart cherry on key enzymes relevant to type 2 diabetes and cardiovascular disease. Food Chem 2018; 252: 142-6.
[http://dx.doi.org/10.1016/j.foodchem.2018.01.084] [PMID: 29478524]
[69]
Homoki JR, Nemes A, Fazekas E, et al. Anthocyanin composition, antioxidant efficiency, and α-amylase inhibitor activity of different Hungarian sour cherry varieties (Prunus cerasus L.). Food Chem 2016; 194: 222-9.
[http://dx.doi.org/10.1016/j.foodchem.2015.07.130] [PMID: 26471548]
[70]
Akkarachiyasit S, Yibchok-Anun S, Wacharasindhu S, Adisakwattana S. In vitro inhibitory effects of cyandin-3-rutinoside on pancreatic α-amylase and its combined effect with acarbose. Molecules 2011; 16(3): 2075-83.
[http://dx.doi.org/10.3390/molecules16032075] [PMID: 21368719]
[71]
Akkarachiyasit S, Charoenlertkul P, Yibchok-Anun S, Adisakwattana S. Inhibitory activities of cyanidin and its glycosides and synergistic effect with acarbose against intestinal α-glucosidase and pancreatic α-amylase. Int J Mol Sci 2010; 11(9): 3387-96.
[http://dx.doi.org/10.3390/ijms11093387] [PMID: 20957102]
[72]
Zhang L, Li J, Hogan S, Chung H, Welbaum GE, Zhou K. Inhibitory effect of raspberries on starch digestive enzyme and their antioxidant properties and phenolic composition. Food Chem 2010; 119: 592-9.
[http://dx.doi.org/10.1016/j.foodchem.2009.06.063]
[73]
Swinburn B, Dietz W, Kleinert S. A lancet commission on obesity. Lancet 2015; 386(10005): 1716-7.
[http://dx.doi.org/10.1016/S0140-6736(15)00722-9] [PMID: 26545418]
[74]
Ravussin E, Galgani JE. The implication of brown adipose tissue for humans. Annu Rev Nutr 2011; 31: 33-47.
[http://dx.doi.org/10.1146/annurev-nutr-072610-145209] [PMID: 21548774]
[75]
Tsuda T, Horio F, Uchida K, Aoki H, Osawa T. Dietary cyanidin 3-O-beta-D-glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice. J Nutr 2003; 133(7): 2125-30.
[http://dx.doi.org/10.1093/jn/133.7.2125] [PMID: 12840166]
[76]
Xie L, Su H, Sun C, Zheng X, Chen W. Recent advances in understanding the anti-obesity activity of anthocyanins and their biosynthesis in microorganisms. Trends Food Sci Technol 2018; 72: 13-24.
[http://dx.doi.org/10.1016/j.tifs.2017.12.002]
[77]
Song H, Wu T, Xu D, Chu Q, Lin D, Zheng X. Dietary sweet cherry anthocyanins attenuates diet-induced hepatic steatosis by improving hepatic lipid metabolism in mice. Nutrition 2016; 32(7-8): 827-33.
[http://dx.doi.org/10.1016/j.nut.2016.01.007] [PMID: 27158052]
[78]
You Y, Yuan X, Liu X, et al. Cyanidin-3-glucoside increases whole body energy metabolism by upregulating brown adipose tissue mitochondrial function. Mol Nutr Food Res 2017; 61(11): 11.
[PMID: 28691397]
[79]
Wei X, Wang D, Yang Y, et al. Cyanidin-3-O-β-glucoside improves obesity and triglyceride metabolism in KK-Ay mice by regulating lipoprotein lipase activity. J Sci Food Agric 2011; 91(6): 1006-13.
[http://dx.doi.org/10.1002/jsfa.4275] [PMID: 21360538]
[80]
Kim HK, Kim JN, Han SN, Nam JH, Na HN, Ha TJ. Black soybean anthocyanins inhibit adipocyte differentiation in 3T3-L1 cells. Nutr Res 2012; 32(10): 770-7.
[http://dx.doi.org/10.1016/j.nutres.2012.06.008] [PMID: 23146774]
[81]
Lee B, Lee M, Lefevre M, Kim HR. Anthocyanins inhibit lipogenesis during adipocyte differentiation of 3T3-L1 preadipocytes. Plant Foods Hum Nutr 2014; 69(2): 137-41.
[http://dx.doi.org/10.1007/s11130-014-0407-z] [PMID: 24682657]
[82]
Guo H, Liu G, Zhong R, Wang Y, Wang D, Xia M. Cyanidin-3-O-β-glucoside regulates fatty acid metabolism via an AMP-activated protein kinase-dependent signaling pathway in human HepG2 cells. Lipids Health Dis 2012; 11: 10.
[http://dx.doi.org/10.1186/1476-511X-11-10] [PMID: 22243683]
[83]
Park S, Kang S, Jeong DY, Jeong SY, Park JJ, Yun HS. Cyanidin and malvidin in aqueous extracts of black carrots fermented with Aspergillus oryzae prevent the impairment of energy, lipid and glucose metabolism in estrogen-deficient rats by AMPK activation. Genes Nutr 2015; 10(2): 455.
[http://dx.doi.org/10.1007/s12263-015-0455-5] [PMID: 25701199]
[84]
Wu T, Yang L, Guo X, Zhang M, Liu R, Sui W. Raspberry anthocyanin consumption prevents diet-induced obesity by alleviating oxidative stress and modulating hepatic lipid metabolism. Food Funct 2018; 9(4): 2112-20.
[http://dx.doi.org/10.1039/C7FO02061A] [PMID: 29632909]
[85]
Wu T, Tang Q, Yu Z, et al. Inhibitory effects of sweet cherry anthocyanins on the obesity development in C57BL/6 mice. Int J Food Sci Nutr 2014; 65(3): 351-9.
[http://dx.doi.org/10.3109/09637486.2013.854749] [PMID: 24224922]
[86]
Tsuda T. Regulation of adipocyte function by anthocyanins; possibility of preventing the metabolic syndrome. J Agric Food Chem 2008; 56(3): 642-6.
[http://dx.doi.org/10.1021/jf073113b] [PMID: 18211021]
[87]
Prior RL, Wu X, Gu L, et al. Purified berry anthocyanins but not whole berries normalize lipid parameters in mice fed an obesogenic high fat diet. Mol Nutr Food Res 2009; 53(11): 1406-18.
[http://dx.doi.org/10.1002/mnfr.200900026] [PMID: 19743407]
[88]
Prior RLE, E Wilkes S, R Rogers T, Khanal RC, Wu X, Howard LR. Purified blueberry anthocyanins and blueberry juice alter development of obesity in mice fed an obesogenic high-fat diet. J Agric Food Chem 2010; 58(7): 3970-6.
[http://dx.doi.org/10.1021/jf902852d] [PMID: 20148514]
[89]
Wu T, Qi X, Liu Y, et al. Dietary supplementation with purified mulberry (Morus australis Poir) anthocyanins suppresses body weight gain in high-fat diet fed C57BL/6 mice. Food Chem 2013; 141(1): 482-7.
[http://dx.doi.org/10.1016/j.foodchem.2013.03.046] [PMID: 23768383]
[90]
Tucakovic L, Colson N, Santhakumar BA, et al. The effects of anthocyanins on body weight and expression of adipocyte’s hormones: leptin and adiponectin. J Funct Foods 2018; 45: 173-80.
[http://dx.doi.org/10.1016/j.jff.2018.03.042]
[91]
Rahim ATMA, Takahashi Y, Yamaki K, Yamaki K. Mode of pancreatic lipase inhibition activity in vitro by some flavonoids and non-flavonoid polyphenols. Food Res Int 2015; 75: 289-94.
[http://dx.doi.org/10.1016/j.foodres.2015.05.017] [PMID: 28454959]
[92]
Yao SL, Xu Y, Zhang YY, Lu YH. Black rice and anthocyanins induce inhibition of cholesterol absorption in vitro. Food Funct 2013; 4(11): 1602-8.
[http://dx.doi.org/10.1039/c3fo60196j] [PMID: 24056583]
[93]
You Q, Chen F, Wang X, Luo PG, Jiang Y. Inhibitory effects of muscadine anthocyanins on α-glucosidase and pancreatic lipase activities. J Agric Food Chem 2011; 59(17): 9506-11.
[http://dx.doi.org/10.1021/jf201452v] [PMID: 21797278]
[94]
Luna-Vital D, Weiss M, Gonzalez de Mejia E. Anthocyanins from purple corn ameliorated tumor necrosis factor-α-induced inflammation and insulin resistance in 3T3-L1 adipocytes via activation of insulin signaling and enhanced GLUT4 translocation. Mol Nutr Food Res 2017; 61(12)1700362
[http://dx.doi.org/10.1002/mnfr.201700362] [PMID: 28759152]
[95]
Gao N, Wang Y, Jiao X, Chou S, Li E, Li B. preparative purification of polyphenols from Aronia melanocarpa (chokeberry) with cellular antioxidant and antiproliferative activity. Molecules 2018; 23(1): 139.
[http://dx.doi.org/10.3390/molecules23010139] [PMID: 29320456]
[96]
Newman DJ, Cragg GM. Natural Products as Sources of New Drugs from 1981 to 2014. J Nat Prod 2016; 79(3): 629-61.
[http://dx.doi.org/10.1021/acs.jnatprod.5b01055] [PMID: 26852623]
[97]
Loizzo MR, Tundis R, Statti GA, Menichini F. Jacaranone: a cytotoxic constituent from Senecio ambiguus subsp. ambiguus (biv.) DC. against renal adenocarcinoma ACHN and prostate carcinoma LNCaP cells. Arch Pharm Res 2007; 30(6): 701-7.
[http://dx.doi.org/10.1007/BF02977631] [PMID: 17679547]
[98]
Venturelli S, Burkard M, Biendl M, Lauer UM, Frank J, Busch C. Prenylated chalcones and flavonoids for the prevention and treatment of cancer. Nutrition 2016; 32(11-12): 1171-8.
[http://dx.doi.org/10.1016/j.nut.2016.03.020] [PMID: 27238957]
[99]
Lee SH, Park SM, Park SM, et al. Induction of apoptosis in human leukemia U937 cells by anthocyanins through down-regulation of Bcl-2 and activation of caspases. Int J Oncol 2009; 34(4): 1077-83.
[PMID: 19287965]
[100]
Rugină D, Hanganu D, Diaconeasa Z, et al. Antiproliferative and apoptotic potential of cyanidin-based anthocyanins on melanoma cells. Int J Mol Sci 2017; 18(5): 949-60.
[http://dx.doi.org/10.3390/ijms18050949] [PMID: 28468289]
[101]
Afaq F, Syed DN, Malik A, et al. Delphinidin, an anthocyanidin in pigmented fruits and vegetables, protects human HaCaT keratinocytes and mouse skin against UVB-mediated oxidative stress and apoptosis. J Invest Dermatol 2007; 127(1): 222-32.
[http://dx.doi.org/10.1038/sj.jid.5700510] [PMID: 16902416]
[102]
Afaq F, Zaid MA, Khan N, Dreher M, Mukhtar H. Protective effect of pomegranate-derived products on UVB-mediated damage in human reconstituted skin. Exp Dermatol 2009; 18(6): 553-61.
[http://dx.doi.org/10.1111/j.1600-0625.2008.00829.x] [PMID: 19320737]
[103]
Chamcheu JC, Afaq F, Syed DN, et al. Delphinidin, a dietary antioxidant, induces human epidermal keratinocyte differentiation but not apoptosis: studies in submerged and three-dimensional epidermal equivalent models. Exp Dermatol 2013; 22(5): 342-8.
[http://dx.doi.org/10.1111/exd.12140] [PMID: 23614741]
[104]
Chinembiri TN, du Plessis LH, Gerber M, Hamman JH, du Plessis J. Review of natural compounds for potential skin cancer treatment. Molecules 2014; 19(8): 11679-721.
[http://dx.doi.org/10.3390/molecules190811679] [PMID: 25102117]
[105]
Kim JE, Kwon JY, Seo SK, et al. Cyanidin suppresses ultraviolet B-induced COX-2 expression in epidermal cells by targeting MKK4, MEK1, and Raf-1. Biochem Pharmacol 2010; 79(10): 1473-82.
[http://dx.doi.org/10.1016/j.bcp.2010.01.008] [PMID: 20096264]
[106]
Murapa P, Dai J, Chung M, Mumper RJ, D’Orazio J. Anthocyanin-rich fractions of blackberry extracts reduce UV-induced free radicals and oxidative damage in keratinocytes. Phytother Res 2012; 26(1): 106-12.
[http://dx.doi.org/10.1002/ptr.3510] [PMID: 21567508]
[107]
Pratheeshkumar P, Son YO, Wang X, et al. Cyanidin-3-glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signaling pathways in SKH-1 hairless mice skin. Toxicol Appl Pharmacol 2014; 280(1): 127-37.
[http://dx.doi.org/10.1016/j.taap.2014.06.028] [PMID: 25062774]
[108]
Kwon JY, Lee KW, Kim JE, et al. Delphinidin suppresses ultraviolet B-induced cyclooxygenases-2 expression through inhibition of MAPKK4 and PI-3 kinase. Carcinogenesis 2009; 30(11): 1932-40.
[http://dx.doi.org/10.1093/carcin/bgp216] [PMID: 19776176]
[109]
Sorrenti V, Vanella L, Acquaviva R, Cardile V, Giofrè S, Di Giacomo C. Cyanidin induces apoptosis and differentiation in prostate cancer cells. Int J Oncol 2015; 47(4): 1303-10.
[http://dx.doi.org/10.3892/ijo.2015.3130] [PMID: 26315029]
[110]
Keravis T, Favot L, Abusnina AA, et al. Delphinidin inhibits tumor growth by acting on VEGF signalling in endothelial cells. PLoS One 2015; 10(12)e0145291
[http://dx.doi.org/10.1371/journal.pone.0145291] [PMID: 26694325]
[111]
Lim W, Jeong W, Song G. Delphinidin suppresses proliferation and migration of human ovarian clear cell carcinoma cells through blocking AKT and ERK1/2 MAPK signaling pathways. Mol Cell Endocrinol 2016; 422: 172-81.
[http://dx.doi.org/10.1016/j.mce.2015.12.013] [PMID: 26704080]
[112]
Wang LS, Hecht SS, Carmella SG, et al. Anthocyanins in black raspberries prevent esophageal tumors in rats. Cancer Prev Res (Phila) 2009; 2(1): 84-93.
[http://dx.doi.org/10.1158/1940-6207.CAPR-08-0155] [PMID: 19139022]
[113]
Faria A, Pestana D, Teixeira D, de Freitas V, Mateus N, Calhau C. Blueberry anthocyanins and pyruvic acid adducts: anticancer properties in breast cancer cell lines. Phytother Res 2010; 24(12): 1862-9.
[http://dx.doi.org/10.1002/ptr.3213] [PMID: 20564502]
[114]
Lala G, Malik M, Zhao C, et al. Anthocyanin-rich extracts inhibit multiple biomarkers of colon cancer in rats. Nutr Cancer 2006; 54(1): 84-93.
[http://dx.doi.org/10.1207/s15327914nc5401_10] [PMID: 16800776]
[115]
Lim S, Xu J, Kim J, et al. Role of anthocyanin-enriched purple-fleshed sweet potato p40 in colorectal cancer prevention. Mol Nutr Food Res 2013; 57(11): 1908-17.
[http://dx.doi.org/10.1002/mnfr.201300040] [PMID: 23784800]
[116]
Bontempo P, de Masi L, Carafa V, et al. Anticancer activities of anthocyanin extract from genotyped Solanum tuberosum L. “Vitelotte. J Funct Foods 2015; 19: 584-93.
[http://dx.doi.org/10.1016/j.jff.2015.09.063]
[117]
Chen XY, Zhou J, Luo LP, et al. Black rice anthocyanins suppress metastasis of breast cancer cells by targeting RAS/RAF/MAPK pathway. BioMed Res Int 2015; 2015414250
[http://dx.doi.org/10.1155/2015/414250] [PMID: 26649302]
[118]
Loizzo MR, Tundis R, Bonesi M, et al. Evaluation of Citrus aurantifolia peel and leaves extracts for their chemical composition, antioxidant and anti-cholinesterase activities. J Sci Food Agric 2012; 92(15): 2960-7.
[http://dx.doi.org/10.1002/jsfa.5708] [PMID: 22589172]
[119]
Wąsik A, Antkiewicz-Michaluk L. The mechanism of neuroprotective action of natural compounds. Pharmacol Rep 2017; 69(5): 851-60.
[http://dx.doi.org/10.1016/j.pharep.2017.03.018] [PMID: 28623709]
[120]
Bagli E, Goussia A, Moschos MM, Agnantis N, Kitsos G. Natural compounds and neuroprotection: mechanisms of action and novel delivery systems. In Vivo 2016; 30(5): 535-47.
[PMID: 27566070]
[121]
Pacheco SM, Soares MSP, Gutierres JM, et al. Anthocyanins as a potential pharmacological agent to manage memory deficit, oxidative stress and alterations in ion pump activity induced by experimental sporadic dementia of Alzheimer’s type. J Nutr Biochem 2018; 56: 193-204.
[http://dx.doi.org/10.1016/j.jnutbio.2018.02.014] [PMID: 29587242]
[122]
Gutierres JM, Carvalho FB, Schetinger MR, et al. Neuroprotective effect of anthocyanins on acetylcholinesterase activity and attenuation of scopolamine-induced amnesia in rats. Int J Dev Neurosci 2014; 33: 88-97.
[http://dx.doi.org/10.1016/j.ijdevneu.2013.12.006] [PMID: 24374256]
[123]
Ma H, Johnson SL, Liu W, et al. Evaluation of polyphenol anthocyanin-enriched extracts of blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry for free radical scavenging, reactive carbonyl species trapping, anti-glycation, anti-β-amyloid aggregation, and microglial neuroprotective effects. Int J Mol Sci 2018; 19(2): 461-80.
[http://dx.doi.org/10.3390/ijms19020461] [PMID: 29401686]
[124]
Chen XY, Huang IM, Hwang LS, Ho CT, Li S, Lo CY. Anthocyanins in blackcurrant effectively prevent the formation of advanced glycation end products by trapping methylglyoxal. J Funct Foods 2014; 8: 259-68.
[http://dx.doi.org/10.1016/j.jff.2014.03.025]
[125]
Thilavech T, Ngamukote S, Belobrajdic D, Abeywardena M, Adisakwattana S. Cyanidin-3-rutinoside attenuates methylglyoxal-induced protein glycation and DNA damage via carbonyl trapping ability and scavenging reactive oxygen species. BMC Complement Altern Med 2016; 16: 138.
[http://dx.doi.org/10.1186/s12906-016-1133-x] [PMID: 27215203]
[126]
Ali T, Kim T, Rehman SU, et al. Natural dietary supplementation of anthocyanins via pi3k/akt/nrf2/ho-1 pathways mitigate oxidative stress, neurodegeneration, and memory impairment in a mouse model of Alzheimer’s disease. Mol Neurobiol 2018; 55(7): 6076-93.
[http://dx.doi.org/10.1007/s12035-017-0798-6] [PMID: 29170981]
[127]
Sohanaki H, Baluchnejadmojarad T, Nikbakht F, Roghani M. Pelargonidin improves memory deficit in amyloid β25-35 rat model of Alzheimer’s disease by inhibition of glial activation, cholinesterase, and oxidative stress. Biomed Pharmacother 2016; 83: 85-91.
[http://dx.doi.org/10.1016/j.biopha.2016.06.021] [PMID: 27470554]
[128]
Brodowska K. Natural flavonoids: classification, potential role, and application of flavonoid analogues. Eur J Biol Res 2017; 7: 108-23.
[http://dx.doi.org/10.5281/zenodo.545778]
[129]
Burdulis D, Šarkinas A, Jasutiené I, Stackevicené E, Nikolajevas L, Janulis V. Comparative study of anthocyanin composition, antimicrobial and antioxidant activity in bilberry (Vaccinium myrtillus L.) and blueberry (Vaccinium corymbosum L.) fruits. Acta Pol Pharm 2009; 66(4): 399-408.
[PMID: 19702172]
[130]
Cisowska A, Wojnicz D, Hendrich AB. Anthocyanins as antimicrobial agents of natural plant origin. Nat Prod Commun 2011; 6(1): 149-56.
[http://dx.doi.org/10.1177/1934578X1100600136] [PMID: 21366068]
[131]
Demirbas A, Yilmaz V, Ildiz N, Baldemir A, Ocsoy I. Anthocyanins-rich berry extracts directed formation of Ag NPs with the investigation of their antioxidant and antimicrobial activities. J Mol Liq 2017; 248: 1044-9.
[http://dx.doi.org/10.1016/j.molliq.2017.10.130]
[132]
Kalt W, McDonald JE, Vinqvist-Tymchuk MR, Liu Y, Fillmore SAE. Human anthocyanin bioavailability: effect of intake duration and dosing. Food Funct 2017; 8(12): 4563-9.
[http://dx.doi.org/10.1039/C7FO01074E] [PMID: 29115354]
[133]
Naz S, Siddiqi R, Ahmad S, Rasool SA, Sayeed SA. Antibacterial activity directed isolation of compounds from Punica granatum. J Food Sci 2007; 72(9): M341-5.
[http://dx.doi.org/10.1111/j.1750-3841.2007.00533.x] [PMID: 18034726]
[134]
Werlein HD, Kütemeyer C, Schatton G, Hubbermann EM, Schwarz K. Influence of elderberry and blackcurrant concentrates on the growth of microorganisms. Food Control 2005; 16: 729-33.
[http://dx.doi.org/10.1016/j.foodcont.2004.06.011]
[135]
Silva S, Costa EM, Mendes M, Morais RM, Calhau C, Pintado MM. Antimicrobial, antiadhesive and antibiofilm activity of an ethanolic, anthocyanin-rich blueberry extract purified by solid phase extraction. J Appl Microbiol 2016; 121(3): 693-703.
[http://dx.doi.org/10.1111/jam.13215] [PMID: 27349348]
[136]
Steiner AD, Vargas A, Fronza N, Brandelli A, Dos Santos JHZ. Antimicrobial activity of some natural extracts encapsulated within silica matrices. Colloids Surf B Biointerfaces 2017; 160: 177-83.
[http://dx.doi.org/10.1016/j.colsurfb.2017.09.028] [PMID: 28934660]
[137]
Maleknia SD, Downard KM. New anthocyanins from black elderberry of inhibitory potential revealed by mass spectrometry. J Nat Prod 2016; 6: 94-02.
[138]
Knox YM, Suzutani T, Yosida I, Azuma M. Anti-influenza virus activity of crude extract of Ribes nigrum L. Phytother Res 2003; 17(2): 120-2.
[http://dx.doi.org/10.1002/ptr.1053] [PMID: 12601672]
[139]
Nikolaeva-Glomb L, Mukova L, Nikolova N, et al. In vitro antiviral activity of a series of wild berry fruit extracts against representatives of Picorna-, Orthomyxo- and Paramyxoviridae. Nat Prod Commun 2014; 9(1): 51-4.
[http://dx.doi.org/10.1177/1934578X1400900116] [PMID: 24660461]
[140]
Li Y, Zhang JJ, Xu DP, et al. Bioactivities and health benefits of wild fruits. Int J Mol Sci 2016; 17(8): 1258.
[http://dx.doi.org/10.3390/ijms17081258] [PMID: 27527154]
[141]
Swaminathan K, Dyason JC, Maggioni A, von Itzstein M, Downard KM. Binding of a natural anthocyanin inhibitor to influenza neuraminidase by mass spectrometry. Anal Bioanal Chem 2013; 405(20): 6563-72.
[http://dx.doi.org/10.1007/s00216-013-7068-x] [PMID: 23748498]
[142]
Noguchi A, Takeda T, Watanabe T, Yasui H. Inhibitory effect of cassis extract against influenza virus infection. J Fac Agr Shinshu U 2008; 44: 1-8.
[143]
Dai J, Wang G, Li W, et al. High-throughput screening for anti-influenza A virus drugs and study of the mechanism of procyanidin on influenza A virus-induced autophagy. J Biomol Screen 2012; 17(5): 605-17.
[http://dx.doi.org/10.1177/1087057111435236] [PMID: 22286278]


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VOLUME: 17
ISSUE: 3
Year: 2020
Published on: 15 July, 2020
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DOI: 10.2174/1570163816666190125152931
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