Flavonoids: an overview

A N Panche, A D Diwan, S R Chandra, A N Panche, A D Diwan, S R Chandra

Abstract

Flavonoids, a group of natural substances with variable phenolic structures, are found in fruits, vegetables, grains, bark, roots, stems, flowers, tea and wine. These natural products are well known for their beneficial effects on health and efforts are being made to isolate the ingredients so called flavonoids. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function. Research on flavonoids received an added impulse with the discovery of the low cardiovascular mortality rate and also prevention of CHD. Information on the working mechanisms of flavonoids is still not understood properly. However, it has widely been known for centuries that derivatives of plant origin possess a broad spectrum of biological activity. Current trends of research and development activities on flavonoids relate to isolation, identification, characterisation and functions of flavonoids and finally their applications on health benefits. Molecular docking and knowledge of bioinformatics are also being used to predict potential applications and manufacturing by industry. In the present review, attempts have been made to discuss the current trends of research and development on flavonoids, working mechanisms of flavonoids, flavonoid functions and applications, prediction of flavonoids as potential drugs in preventing chronic diseases and future research directions.

Keywords: AChE, acetylcholinesterase; AD, Alzheimer's disease; Aβ, amyloid protein; BACE-1, β active site cleavage enzyme-1; BChE, butyrylcholinsterase; Biological activity; COX, cyclo-oxygenase; Flavonoids; Future research directions; NDM-1, New Delhi metallo-β-lactamase-1; Research trends; Structure and composition; XO, xanthine oxidase.

Figures

Fig. 1.
Fig. 1.
Basic skeleton structure of flavonoids and their classes.
Fig. 2.
Fig. 2.
Flavonoid classes, subclasses and natural sources.
Fig. 3.
Fig. 3.
Cumulative representation of roles of flavonoids in various bioactivities, human health and agriculture. BChE, butyrylcholinesterase; AChE, acetylcholinesterase; BACE-1, β active site cleavage enzyme-1; NDM-1, New Delhi metallo-β-lactamase-1; H1N1, haemagglutinin 1 neuraminidase 1.

References

    1. Burak M & Imen Y (1999) Flavonoids and their antioxidant properties. Turkiye Klin Tip Bil Derg 19, 296–304.
    1. Ovando C, Hernandez D, Hernandez E, et al. (2009) Chemical studies of anthocyanins: a review. Food Chem 113, 859–871.
    1. Lee Y, Yuk D, Lee J, et al. (2009) Epigallocatechin-3-gallate prevents lipopolysaccharide-induced elevation of β-amyloid generation and memory deficiency. Brain Res 1250, 164–174.
    1. Metodiewa D, Kochman A & Karolczak S (1997) Evidence for antiradical and antioxidant properties of four biologically active N, N, diethylaminoethyl ethers of flavanone oximes: a comparison with natural polyphenolic flavonoid (rutin) action. Biochem Mol Biol Int 41, 1067–1075.
    1. Hayashi T, Sawa K, Kawasaki M, et al. (1988) Inhibition of cow's milk xanthine oxidase by flavonoids. J Nat Prod 51, 345–348.
    1. Walker E, Pacold M, Perisic O, et al. (2000) Structural determinations of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol Cell 6, 909–919.
    1. Havsteen B (2002) The biochemistry and medical significance of the flavonoids. Pharmacol Ther 96, 67–202.
    1. Dewick PM (2001) The shikimate pathway: aromatic amino acids and phenylpropanoids In Medicinal Natural Products: a Biosynthetic Approach, 2nd ed., pp. 137–186 [Dewick PM, editor]. Chichester: John Wiley.
    1. Griesbach R (2005) Biochemistry and genetics of flower color. Plant Breed Rev 25, 89–114.
    1. Takahashi A & Ohnishi T (2004) The significance of the study about the biological effects of solar ultraviolet radiation using the exposed facility on the international space station. Biol Sci Space 18, 255–260.
    1. Samanta A, Das G & Das S (2011) Roles of flavonoids in plants. Int J Pharm Sci Tech 6, 12–35.
    1. Jorgensen R (1995) Co-suppression, flower color patterns, and metastable gene expression states. Science 268, 686–691.
    1. Dixon R & Pasinetti G (2010) Flavonoids and isoflavonoids: from plant biology to agriculture and neuroscience. Plant Physiol 154, 453–457.
    1. Kumar S & Pandey AK (2013) Chemistry and biological activities of flavonoids: an overview. ScientificWorldJournal 2013, 162750.
    1. Panche A, Chandra S, Diwan A, et al. (2015) Alzheimer's and current therapeutics: a review. Asian J Pharm Clin Res 8, 14–19.
    1. Manach C, Scalbert A, Morand C, et al. (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79, 727–747.
    1. Iwashina T (2013) Flavonoid properties of five families newly incorporated into the order Caryophyllales (Review). Bull Natl Mus Nat Sci 39, 25–51.
    1. Matthies A, Clavel T, Gütschow M, et al. (2008) Conversion of daidzein and genistein by an anaerobic bacterium newly isolated from the mouse intestine. Appl Envrion Microbiol 74, 4847–4852.
    1. Aoki T, Akashi T & Ayabe S (2000) Flavonoids of leguminous plants: structure, biological activity, and biosynthesis. J Plant Res 113, 475–488.
    1. Dixon R & Ferreira D (2002) Molecules of interest: genistein. Phytochemistry 60, 205–211.
    1. Szkudelska K & Nogowski L (2007) Genistein – a dietary compound inducing hormonal and metabolic changes. J Steroid Biochem Mol Biol 105, 37–45.
    1. Linuma M, Tanaka T, Hamada K, et al. (1987) Revised structure of neoflavone in Coutarea hexandra. Phytochemistry 26, 3096–3097.
    1. Nishimura S, Taki M, Takaishi S, et al. (2000) Structures of 4-aryl-coumarin (neoflavone) dimers isolated from Pistacia chinensis BUNGE and their estrogen-like activity. Chem Pharm Bull (Tokyo) 48, 505–508.
    1. Garazd M, Garazd Y & Khilya V (2003) Neoflavones. 1. Natural distribution and spectral and biological properties. Chem Nat Comp 39, 54–121.
    1. Giusti M & Wrolstad R (2003) Acylated anthocyanins from edible sources and their applications in food systems. Biochem Eng J 14, 217–225.
    1. Hertog MG, Hollman PC & Van De PB (1993) Content of potentially anticarcinogenic flavonoids of tea infusions, wines, and fruit juices. J Agric Food Chem 41, 1242–1246.
    1. Justesen U & Knuthsen P (2001) Composition of flavonoids in fresh herbs and calculation of flavonoid intake by use of herbs in traditional Danish dishes. Food Chem 73, 245–250.
    1. Stewart AJ, Bozonnet S, Mullen W, et al. (2000) Occurrence of flavonols in tomatoes and tomato-based products. J Agric Food Chem 48, 2663–2669.
    1. Zheng W & Wang SY (2001) Antioxidant activity and phenolic compounds in selected herbs. J Agric Food Chem 49, 5165–5170.
    1. Atanassova M & Bagdassarian V (2009) Rutin content in plant products. J Univ Chem Tech Met 44, 201–203.
    1. Gudrais E (2012) Curbing clots. Harvard magazine. (accessed June 2016).
    1. Chang S, Tan C, Frankel E, et al. (2000) Low-density lipoprotein antioxidant activity of phenolic compounds and polyphenol oxidase activity in selected clingstone peach cultivars. J Agric Food Chem 48, 147–151.
    1. Malagutti AR, Zuin V, Cavalheiro É, et al. (2006) Determination of rutin in green tea infusions using square-wave voltammetry with a rigid carbon–polyurethane composite electrode. Electroanalysis 18, 1028–1034.
    1. Khan MT, Orhan I & Enol SS (2009) Cholinesterase inhibitory activities of some flavonoid derivatives and chosen xanthone and their molecular docking studies. Chem Biol Interact 181, 383–389.
    1. Thompson LU, Boucher BA, Liu Z, et al. (2006) Phytoestrogen content of foods consumed in Canada, including isoflavones, lignans, and coumestan. Nutr Cancer 54, 184–201.
    1. Umpress ST, Murphy SP, Franke AA, et al. (2005) Isoflavone content of foods with soy additives. J Food Comp Anal 18, 533–550.
    1. Krenn L, Unterrieder I & Ruprechter R (2002) Quantification of isoflavones in red clover by high-performance liquid chromatography. J Chromatgr B 777, 123–128.
    1. Coward L, Barnes NC, Setchell K, et al. (1993) Genistein, daidzein, and their β-glycoside conjugates: antitumor isoflavones in soybean foods from American and Asian diets. J Agric Food Chem 41, 1961–1967.
    1. Kaufman PB, Duke JA, Brielmann H, et al. (1997) A comparative survey of leguminous plants as sources of the isoflavones, genistein and daidzein: implications for human nutrition and health. J Altern Complement Med 3, 7–12.
    1. Gálvez MC, Barroso CG & Pérez-Bustamante JA (1994) Analysis of polyphenolic compounds of different vinegar samples. Z Lebensm Unters F A 199, 29–31.
    1. Zhang Y, Wang GJ, Song TT, et al. (1999) Urinary disposition of the soybean isoflavones daidzein, genistein and glycitein differs among humans with moderate fecal isoflavone degradation activity. J Nutr 129, 957–962.
    1. Cerezoa AB, Tesfayea W, Soria-Díazb ME, et al. (2010) Effect of wood on the phenolic profile and sensory properties of wine vinegars during ageing. J Food Comp Anal 23, 175–184.
    1. Felgines C, Texier O, Morand C, et al. (2000) Bioavailability of the flavanone naringenin and its glycosides in rats. Am J Physiol Gastrointest Liver Physiol 279, G1148–G1154.
    1. Rathmell WG & Bendall DS (1971) Phenolic compounds in relation to phytoalexin biosynthesis in hypocotyls of Phaseolus vulgaris. Physiol Plant Pathol 1, 351–362.
    1. Cruickshank IA, Biggs DR, Dawn PR, et al. (1974) Phaseollin and phaseollidin relationships in infection-droplets on endocarp of Phaseolus vulgaris. Physiol Plant Pathol 4, 261–276.
    1. Hvattum E (2002) Determination of phenolic compounds in rose hip (Rosa canina) using liquid chromatography coupled to electrospray ionisation tandem mass spectrometry and diode-array detection. Rapid Commun Mass Spectrom 16, 655–662.
    1. Sahu BD, Kalvala AK, Koneru M, et al. (2014) Ameliorative effect of fisetin on cisplatin-induced nephrotoxicity in rats via modulation of NF-κB activation and antioxidant defence. PLOS ONE 9, e105070.
    1. Leung LK, Su Y, Chen R, Zhang Z, et al. (2001) Theaflavins in black tea and catechins in green tea are equally effective antioxidants. J Nutr 131, 2248–2251.
    1. Truong V-D, Deighton N, Thompson RT, et al. (2010) Characterization of anthocyanins and anthocyanidins in purple-fleshed sweetpotatoes by HPLC-DAD/ESI-MS/MS. J Agric Food Chem 58, 404–410.
    1. Andreeva OA, Ivashev MN, Ozimina II, et al. (1998) Diosmetin glycosides from Caucasian vetch: isolation and study of biological activity. Pharm Chem J 32, 595–597.
    1. Cai H, Al-Fayez M, Tunstall RG, et al. (2005) The rice bran constituent tricin potently inhibits cyclooxygenase enzymes and interferes with intestinal carcinogenesis in ApcMin mice. Mol Cancer Ther 4, 1287–1292.
    1. Medjakovic S & Jungbauer A (2008) Red clover isoflavones biochanin A and formononetin are potent ligands of the human aryl hydrocarbon receptor. J Steroid Biochem Mol Biol 108, 171–177.
    1. National Agricultural Library (2014) Dr Duke's Phytochemical and Ethnobotanical Databases. Citrus aurantium L. (accessed June 2016).
    1. Arts IC, Van De PB & Hollman PC (2000) Catechin content of foods commonly consumed in the Netherlands. J Agric Food Chem 48, 1752–1757.
    1. Ross JA & Kasum CM (2002) Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr 22, 19–34.
    1. Basli A, Soulet S, Chaher N, et al. (2012) Wine polyphenols: potential agents in neuroprotection. Oxid Med Cell Longev 2012, 805762.
    1. Grayer RJ & Veitch NC (2006) Flavanones and dihydroflavonols In Flavonoids: Chemistry, Biochemistry and Applications, pp. 918–1002 [Anderson OM and Markham KR, editors]. Boca Raton, FL: CRC Press/Taylor & Francis Group.
    1. Kawaii S, Tomono Y, Katase E, et al. (1999) Quantitation of flavonoid constituents in citrus fruits. J Agric Food Chem 47, 3565–3571.
    1. Calderon-Montaño JM, Burgos-Moron E, Perez-Guerrero C, et al. (2011) A review on the dietary flavonoid kaempferol. Mini Rev Med Chem 11, 298–344.
    1. Liu RH (2013) Health-promoting components of fruits and vegetables in the diet. Adv Nutr 4, 384S–392S.
    1. Kim SH & Choi KC (2013) Anti-cancer effect and underlying mechanism(s) of kaempferol, a phytoestrogen, on the regulation of apoptosis in diverse cancer cell models. Toxicol Res 29, 229–234.
    1. Kayoko S, Hisae O, Michiyo F, et al. (1998) Intestinal absorption of luteolin and luteolin 7-O-β-glucoside in rats and humans. FEBS Lett 438, 220–224.
    1. López-Lázaro M (2009) Distribution and biological activities of the flavonoid luteolin. Mini Rev Med Chem 9, 31–59.
    1. Perry EK, Tomlinson BE, Blessed G, et al. (1978) Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 2, 1457–1459.
    1. Sheng R, Lin X, Zhang J, et al. (2009) Design, synthesis and evaluation of flavonoid derivatives as potent AChE inhibitors. Bioorg Med Chem 17, 6692–6698.
    1. Smith R, DeWitt D & Garavito R (2000) Cyclooxygenases: structural, cellular and molecular biology. Ann Rev Biochem 69, 145–182.
    1. Kurumbail R, Stevens A, Gierse J, et al. (1996) Structural basis for selective inhibition of cyclooxygenase 2 by anti-inflammatory agents. Nature 384, 644–648.
    1. Kujubu D, Fletcher B, Varnum B, et al. (1991) TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J Biol Chem 266, 12866–12872.
    1. D'Mello P, Gadhwal M, Joshi U, et al. (2011) Modeling of COX-2 inhibitory activity of flavonoids. Int J Pharm Pharm Sci 3, 33–40.
    1. Madeswaran A, Umamaheswari M, Asokkumar K, et al. (2012) In-silico docking studies of cyclooxygenase inhibitory activity of commercially available flavonoids. Asian J Pharm Life Sci 2, 174–181.
    1. Madeswaran A, Umamaheswari M, Asokkumar K, et al. (2011) In-silico docking studies of lipoxygenase inhibitory activity of commercially available flavonoids. J Comput Method Mol Des 1, 65–72.
    1. Wu C, Wu S, Chung W, et al. (2007) Antiplatelet effect and selective binding to cyclooxygenase (COX) by molecular docking analysis of flavonoids and lignans. Int J Mol Sci 8, 830–841.
    1. Hatti K, Diwakar L, Rao G, et al. (2009) Abyssinones and related flavonoids as potential steroidogenesis modulators. Bioinformation 3, 399–402.
    1. Borges F, Fernandes E & Roleira F (2002) Progress towards the discovery of xanthine oxidase inhibitors. Curr Med Chem 9, 195–217.
    1. Hille R (1996) The mononuclear molybdenum enzymes. Chem Rev 96, 2757–2816.
    1. Alnajjar B (2008) Computational studies of natural flavonoids towards the discovery of a potential xanthine oxidase inhibitor. MSc Thesis, Universiti Sains, Malaysia.
    1. Umamaheswari M, Madeswaran A, Kuppusamy A, et al. (2011) Discovery of potential xanthine oxidase inhibitors using in silico docking studies. Der Pharma Chemica 3, 240–247.
    1. Shoba G, Hari S, Prabhavathi G, et al. (2010) Flavonoids – natural therapeutic agents for polycystic kidney disease. Int J Pharm Bio Sci 1, B89–B105.
    1. Lin W, Xie J, Wu X, et al. (2014) Inhibition of xanthine oxidase activity by gnaphalium affine extract. Chin Med Sci J 29, 225–230.
    1. De Souza V, De Franco E, De Araujo M, et al. (2016) Characterization of the antioxidant activity of aglycone and glycosylated derivatives of hesperetin: an in-vitro and in-vitro study. J Mol Recognit 29, 80–87.
    1. Lee J, Jeong K, Shin S, et al. (2011) Antimicrobial natural products as β-ketoacyl-acyl carrier protein synthase III inhibitors. Bioorg Med Chem 17, 5408–5413.
    1. Ganugapati J, Sirisha V, Mukkavalli S, et al. (2011) Insilico modeling and docking studies of New Delhi metallo β lactamase-1 (super bug). Int J Eng Sci Tech 3, 2427–2434.
    1. Padmavathi M, Prasanth Reddy V & Rao R (2012) Inhibition of NDM-1 in superbugs by flavonoids – an insilico approach. J Adv Bioinfo App Res 3, 328–332.
    1. Ganugapati J, Mukkavalli S & Sahithi A (2011) Docking studies of green tea flavonoids as insulin mimetics. Int J Comp App 30, 48–52.
    1. Lu S & Chong F (2012) Combining molecular docking and molecular dynamics to predict the binding modes of flavonoid derivatives with the neuraminidase of the 2009 H1N1 influenza A virus. Int J Mol Sci 13, 4496–4507.
    1. Cardenas H, Arango D, Nicholas C, et al. (2016) Dietary apigenin exerts immune-regulatory activity in vivo by reducing NF-κB activity, halting leukocyte infiltration and restoring normal metabolic function. Int J Mol Sci 17, 323.
    1. Kim K, Vance TM & Chun OK (2016) Greater flavonoid intake is associated with improved CVD risk factors in US adults. Br J Nutr 115, 1481–1488.
    1. Mulvihill E, Burke A & Huff M (2016) Citrus flavonoids as regulators of lipoprotein metabolism and atherosclerosis. Annu Rev Nutr 36, 275–299.
    1. Hügel HM, Jackson N, May B, et al. (2016) Polyphenol protection and treatment of hypertension. Phytomedicine 23, 220–231.
    1. Brüll V, Burak C, Stoffel-Wagner B, et al. (2015) Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-) hypertension: a randomised double-blinded placebo-controlled cross-over trial. Br J Nutr 114, 1263–1277.
    1. Schiavano GF, De Santi M, Brandi G, et al. (2015) Inhibition of breast cancer cell proliferation and in vitro tumorigenesis by a new red apple cultivar. PLOS ONE 10, e0135840.
    1. Wallace TC, Slavin M & Frankenfel CL (2016) Systematic review of anthocyanins and markers of cardiovascular disease. Nutrients 8, 32.
    1. Pribac G, Sferdian M, Neamţu C, et al. (2015) Fenugreek powder exerts protective effects on alcoholised rat's kidney, highlighted using ultrastructural studies. Rom J Morphol Embryol 56, 445–451.
    1. da Silva SM, Koehnlein EA, Bracht A, et al. (2014) Inhibition of salivary and pancreatic α-amylases by a pinhão coat (Araucaria angustifolia) extract rich in condensed tannin. Food Res Int 56, 1–8.
    1. Oliveira R, Gonçalves G, Inácio F, et al. (2015) Inhibition of pancreatic lipase and triacylglycerol intestinal absorption by a pinhão coat (Araucaria angustifolia) extract rich in condensed tannin. Nutrients 7, 5601–5614.
    1. Hayden E, Yamin G, Beroukhim S, et al. (2015) Inhibiting amyloid β-protein assembly: size–activity relationships among grape seed-derived polyphenols. J Neurochem 135, 416–430.
    1. Paris D, Mathura V, Ghezala G, et al. (2011) Flavonoids lower Alzheimer's Aβ production via an NFκB dependent mechanism. Bioinformation 6, 229–236.
    1. Alzheimer's Disease International (2011) World Alzheimer Report 2010. The Global Economic Impact of Dementia. London: Alzheimer's Disease International.
    1. Terry R, Masliah E, Salmon D, et al. (1991) Physical basis of cognitive alterations in Alzheimer's disease: synapse loss in the major correlate of cognitive impairment. Ann Neurol 30, 572–580.
    1. Shimmyo Y, Kihara T, Akaike A, et al. (2008) Flavonols and flavones as BACE-1 inhibitors: structure–activity relationship in cell-free, cell-based and in-silico studies reveal novel pharmacophore features. Biochem Biophy Acta 1780, 819–825.
    1. Swaminathan M, Chin F, Sek P, et al. (2014) Flavonoids with M1 muscarinic acetylcholine receptor binding activity. Molecules 19, 8933–8948.
    1. Fisher A (2008) Cholinergic treatments with emphasis on M1 muscarinic agonists as potential disease-modifying agents for Alzheimer's disease. Neurotherapeutics 5, 433–442.
    1. DeGroot H (1994) Reactive oxygen species in tissue injury. Hepatogastroenterology 41, 328–332.
    1. Grace PA (1994) Ischaemia–reperfusion injury. Br J Surg 81, 637–647.
    1. Halliwell B (1995) How to characterize an antioxidant: an update. Biochem Soc Symp 61, 73–101.
    1. Nijveldt R, Nood E, Hoorn D, et al. (2001) Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 74, 418–425.
    1. Codorniu-Hernández E, Rolo-Naranjoa A & Montero-Cabrera LA (2007) Theoretical affinity order among flavonoids and amino acid residues: an approach to understand flavonoid–protein interactions. J Mol Struc: THEOCHEM 819, 121–129.
    1. Korkina L & Afanasev I (1997) Antioxidant and chelating properties of flavonoids. Adv Pharmacol 38, 151–163.
    1. Hanasaki Y, Ogawa S & Fukui S (1994) The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radic Biol Med 16, 845–850.
    1. Kerry N & Abbey M (1997) Red wine and fractionated phenolic compounds prepared from red wine inhibit low density lipoprotein oxidation in vitro. Atherosclerosis 135, 93–102.
    1. Sanhueza J, Valdes J, Campos R, et al. (1992) Changes in the xanthine dehydrogenase/xanthine oxidase ratio in the rat kidney subjected to ischemia–reperfusion stress: preventive effect of some flavonoids. Res Commun Chem Pathol Pharmacol 78, 211–218.
    1. Shoskes D (1998) Effect of bioflavonoids quercetin and curcumin on ischemic renal injury: a new class of renoprotective agents. Transplantation 66, 147–152.
    1. Chang W, Lee Y, Lu F, et al. (1993) Inhibitory effects of flavonoids on xanthine oxidase. Anticancer Res 13, 2165–2170.
    1. Cos P, Ying L, Calomme M, et al. (1998) Structure–activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. J Nat Prod 61, 71–76.
    1. Friesenecker B, Tsai A, Allegra C, et al. (1994) Oral administration of purified micronized flavonoid fraction suppresses leukocyte adhesion in ischemia–reperfusion injury: in-vitro observations in the hamster skin fold. Int J Microcirc Clin Exp 14, 50–55.
    1. Friesenecker B, Tsai A & Intaglietta M (1995) Cellular basis of inflammation, edema and the activity of Daflon 500 mg. Int J Microcirc Clin Exp 15, 17–21.
    1. Ferrandiz M, Gil B & Sanz M (1996) Effect of bakuchiol on leukocyte functions and some inflammatory responses in mice. J Pharm Pharmacol 48, 975–980.
    1. Alcaraz M & Ferrandiz M (1987) Modification of arachidonic metabolism by flavonoids. J Ethnopharmacol 21, 209–229.
    1. Jager A & Saaby L (2011) Flavonoids and the CNS. Molecules 16, 1471–1485.
    1. Hu Y, Yanhong S, Jing Z, et al. (2009) Synthesis and biological evaluation of novel flavonoid derivatives as dual binding acetylcholinesterase inhibitors. J Enzyme Inhib Med Chem 24, 372–380.
    1. Croteau R, Kutchan TM & Lewis NG (2000) Natural products (secondary metabolites) In Biochemistry and Molecular Biology of Plants, pp. 1250–1318 [Buchanan B, Gruissem W and Jones R, editors]. Rockville, MD: American Society of Plant Biologists.
    1. Wink M (2004) Phytochemical diversity of secondary metabolites In Encyclopedia of Plant and Crop Science, pp. 915–919. New York: Marcel Dekker, Inc.
    1. Anand S (2010) Various approaches for secondary metabolite production through plant tissue culture. Pharmacia 1, 1–7.
    1. Hussain MS, Fareed S, Ansari S, et al. (2012) Current approaches toward production of secondary plant metabolites. J Pharm Bioallied Sci 4, 10–20.
    1. Srivastava N & Bezwada R (2015) Flavonoids: The Health Boosters. White Paper. Hillsborough, NJ: Indofine Chemical Company.
    1. Hossain H, Shahid-Ud-Daula A, Jahan I, et al. (2012) Evaluation of antinociceptive and antioxidant potential from the leaves of Spilanthes paniculata growing in Bangladesh. Int J Pharm Phytopharmacol Res 1, 178–186.
    1. Snijman P, Swanevelder S, Joubert S, et al. (2007) The antimutagenic activity of the major flavonoids of rooibos (Aspalathus linearis): some dose–response effects on mutagen activation–flavonoid interactions. Mutat Res 631, 111–123.
    1. LeJeune TM, Tsui HY, Parsons LB, et al. (2015) Mechanism of action of two flavone isomers targeting cancer cells with varying cell differentiation status. PLOS ONE 10, e0142928.
    1. Kim H, Son K, Chang H, et al. (2004) Anti-inflammatory plant flavonoids and cellular action mechanisms. J Pharmacol Sci 96, 229–245.
    1. Ren W, Qiao Z, Wang H, et al. (2003) Flavonoids: promising anticancer agents. Med Res Rev 23, 519–534.
    1. Kitagawa S, Fujisawa H & Sakurai H (1992) Scavenging effects of dihydric and polyhydric phenols on superoxide anion radicals, studied by electron spin resonance spectrometry. Chem Pharm Bull 40, 304–307.
    1. Lale A, Herbert J, Augereau J, et al. (1996) Ability of different flavonoids to inhibit the procoagulant activity of adherent human monocytes. J Nat Prod 59, 273–276.
    1. Hertog M, Sweetnam P, Fehily A, et al. (1997) Antioxidant flavonols and ischemic heart disease in a Welsh population of men: the Caerphilly Study. Am J Clin Nutr 65, 1489–1494.
    1. Haraguchi H, Saito T, Ishikawa H, et al. (1996) Antiperoxidative components in Thymus vulgaris. Planta Med 62, 217–221.
    1. Ishikawa T, Suzukawa M, Ito T, et al. (1997) Effect of tea flavonoid supplementation on the susceptibility of low-density lipoprotein to oxidative modification. Am J Clin Nutr 66, 261–266.
    1. Katan MB & Hollman PCH (1998) Dietary flavonoids and cardiovascular disease. Nutr Metab Cardiovasc Dis 8, 1–4.
    1. Pietta PG (2000) Flavonoids as antioxidants. J Nat Prod 63, 1035–1042.
    1. Halliwell B (1991) Drug antioxidant effects. A basis for drug selection? Drugs 42, 569–605.
    1. Halliwell B (1991) Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med 91, 14S–22S.
    1. Halliwell B, Gutteridge J & Cross C (1992) Free radicals, antioxidants, and human disease: where are we now? J Lab Clin Med 119, 598–620.
    1. Letan A (1966) The relation of structure to antioxidant activity of quercetin and some of its derivatives. J Food Sci 31, 395–399.
    1. Wang H, Xia Y, Yang Z, et al. (1998) Recent advances in the discovery and development of flavonoids and their analogues as antitumor and anti-HIV agents. Adv Exp Med Biol 439, 191–225.
    1. Kaul T, Middleton E & Ogra P (1985) Antiviral effect of flavonoids on human viruses. J Med Virol 15, 71–79.
    1. Wu D, Kong Y, Han C, et al. (2008) d-Alanine: d-alanine ligase as a new target for the flavonoids quercetin and apigenin. Int J Antimicrob Agents 32, 421–426.
    1. Li M & Xu Z (2008) Quercetin in a lotus leaves extract may be responsible for antibacterial activity. Arch Pharm Res 31, 640–644.
    1. Wiseman H (2000) The therapeutic potential of phytoestrogens. Exp Opin Investig Drugs 9, 1829–1840.
    1. Metzner J, Frank T, Kunz I, et al. (2009) Study on the pharmacokinetics of synthetic genistein after multiple oral intake in post-menopausal women. Arzneimittelforschung 59, 513–520.
    1. Tikkanen MJ & Adlercreutz H (2000) Dietary soy-derived isoflavone phytoestrogens. Could they have a role in coronary heart disease prevention? Biochem Pharmacol 60, 1–5.
    1. Tham D, Gardner C & Haskell W (1998) Clinical review 97: potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological and mechanistic evidence. J Clin Endocrinol Metab 83, 2223–2235.
    1. Comalada M, Camuesco D, Sierra S, et al. (2005) In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-κB pathway. Eur J Immunol 35, 584–592.
    1. Fotsis T, Pepper M, Aktas E, et al. (1997) Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis. Cancer Res 57, 2916–2921.
    1. Si H & Liu D (2007) Phytochemical genistein in the regulation of vascular function: new insights phytochemical genistein in the regulation of vascular function: new insights. Curr Med Chem 14, 2581–2589.
    1. Kamaraj S, Ramakrishnan G, Anandakumar P, et al. (2009) Antioxidant and anticancer efficacy of hesperidin in benzo (a)pyrene induced lung carcinogenesis in mice. Invest New Drugs 27, 214–222.
    1. Arafa S, Zhu Q, Barakat B, et al. (2009) Tangeretin sensitizes cisplatin-resistant human ovarian cancer cells through down regulation of phosphoinositide 3-kinase/Akt signaling pathway. Cancer Res 69, 8910–8917.
    1. Huang JH, Huang CC, Fang JY, et al. (2010) Protective effects of myricetin against ultraviolet-B-induced damage in human keratinocytes. Toxicol In Vitro 24, 21–28.
    1. Beking K & Vieira A (2010) Flavonoid intake and disability-adjusted life years due to Alzheimer's and related dementias: a population-based study involving twenty-three developed countries. Public Health Nutr 13, 1403–1409.
    1. Hwang S & Yen G (2008) Neuroprotective effects of the citrus flavanones against H2O2-induced cytotoxicity in PC12 cells. J Agric Food Chem 56, 859–864.
    1. Waisundara V, Hsu A, Tan B, et al. (2009) Baicalin reduces mitochondrial damage in streptozotocin-induced diabetic Wistar rats. Diabetes Metab Res Rev 25, 671–677.
    1. Zhang L, Jie G, Zhang J, et al. (2009) Significant longevity-extending effects of EGCG on Caenorhabditis elegans under stress. Free Radic Biol Med 46, 414–421.
    1. Meng Q, Velalar C & Ruan R (2008) Effects of epigallocatechin-3-gallate on mitochondrial integrity and antioxidative enzyme activity in the aging process of human fibroblast. Free Radic Biol Med 44, 1032–1041.
    1. Saul N, Pietsch K, Menzel R, et al. (2009) Catechin induced longevity in C. elegans: from key regulator genes to disposable soma. Mech Ageing Dev 130, 477–486.

Source: PubMed

3
订阅