2012, Number 5
<< Back Next >>
Salud Mental 2012; 35 (5)
Los flavonoides y el Sistema Nervioso Central
Estrada-Reyes R, Ubaldo-Suárez D, Araujo-Escalona AG
Language: Spanish
References: 78
Page: 375-384
PDF size: 218.25 Kb.
ABSTRACT
The aim of the present study was to show the most relevant aspects of
the flavonoids such as their origin, sources, chemical structures, and
metabolism in the body human. We offer a brief review about their
antiallergic, anti-cancer, anti-inflammatory, and analgesic properties.
This review shows their effects on CNS and evidences their pharmacologic
potential in the therapeutics of the mental disorders.
Flavonoids may have existed in nature for over 1 billion years
and thus have interacted with evolving organisms. These compounds
are molecules of low molecular mass, abundant in all berries and
citric fruits, chocolate, nuts, red wine, and several medicinal plants.
Flavonoids interact with several enzymes responsible for the transport
of xenobiotics to the brain, which are considering modifiers of the
biological response. Perhaps the most studied have been their anti-oxidant
properties, which have met reflected in his capacity to protect to
the cells of the oxidative stress, implicated several pathologies associated
with aging, such as Alzheimer’s and Parkinson’s diseases.
In the last 30 years, a intensive research about the effects of the
flavonoids on CNS has been carried out; in this regard, flavonoids
have showed effective effects as anxiolytic, antidepressants, and
anticonvulsive drugs, and although their actions in the CNS occur
through a variety of interactions with different receptors and signaling
pathways, it has been demonstrated that these effects are mediated
principally by GABA, in particular GABA
A receptors, which these has
led them to being postulates as a new benzodiazepines family, but
without the side effects of these.
REFERENCES
Tomás-Barberán FA, Wollenweber E. Flavonoid aglycones from the leaf surfaces of some Labiatae species. Plant Syst Evol 1990;173(3-4):109-118.
Harborne JB (editores). The flavonoids, advances in research since 1986. Londres: Chapman & Hall; 1994.
Manuchair E. Pharmacodynamic basis of herbal medicine. USA: CRC Press; 2001.
Németh K, Plumb GW, Berrin JG, Juge N et al. Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr 2003;42:29-42.
Day AJ, Canada FJ, Diaz JC, Kroon PA et al. Dietary flavonoid and isoflavone glycosides are hydrolyzed by the lactase site of lactase phlorizin hydrolase. FEBS Lett. 2000;468:166-170.
Berrin JG, McLauchlan WR, Needs P, Williamson G et al. Functional expression of human liver cytosolic beta-glucosidase in Pichia pastoris. Insights into its role in the metabolism of dietary glucosides. Eur J Biochem 2002;269:249-258.
Hollman PC. H. Absorption, bioavailability, and metabolism of flavonoids. Arch Physiol Biochem 2004;42:74-83.
Manach C, Scalbert A, Morand C, Remesy C et al. Polyphenols: food sources and bioavailability. Am J Clin Nutr 2004;79:727-747.
Spencer JPE, Chowrimootoo G, Choudhury R, Debnam ES et al. The small intestine can both absorb and glucuronidate luminal flavonoids. FEBS Lett 1999;458:224-230.
Crespy V, Morand C, Besson C, Manach C et al. Comparison of the intestinal absorption of quercetin, phloretin and their glucosides in rats. J Nutr 2001;131:2109-2114.
De Boer AG, Gaillard PJ. Drug targeting to the brain. Annu Rev Pharmacol Toxicol 2007;47:323-355.
Rang H, Dale M, Ritter J, Moore P. Pharmacology. Sexta edición. Edinburgh, UK: ed. Churchill Livingstone; 2007.
Wieland HA, Luddens H, Seeburg PH. A single histidine in Gaba-A receptors is essential for benzodiazepine agonist binding. J Biol Chem 1992;267:1426-1429.
Bruton R, Qume M. [3H]-GABA binding to GABA-A and GABAB sites on rat brain crude synaptic membranes. Methods Mol Biol 1999;106:27-35.
Jäger AK, Saaby L. Flavonoids and the CNS. Molecules 2011;16:1471-1485.
Álvarez de Felipe AI, Pulido Duarte MM. Transportadores de tipo ABC: consecuencias de su interacción con flavonoides. BLACPMA 2008;7(6):296-311.
Versantvoort CH, Schuurhuis GJ, Pinedo HM, Bekman CA et al. Genistein modulates the decreased drug accumulation in non-pglycoprotein mediated multidrug resistant tumor cells-. Br J Cancer 1993;68:939-946.
Ferraro HK, Namgoong SY, Kim HP. Biological actions of flavonoids. Arc Pharmacol Res 1993;16:18-27.
Paul P, Ritra J, Ritva S, Mackku H. Dietary flavonoids and risk of lung cancer and other malignant neoplasms. Am J Epidemiol 1997;146:223-230.
Felicia VS, Najla GPC, Madeleine M, Keneeth KC. Inhibition of Human Breast cancer cell proliferation and delay of mammary tumorigenisis by flavonoids and citrus juices. Nutr Cancer 1996;26:167-181.
Fritz B, Tobias S, Albrecht K, Chaelotte B et al. Selected novel flavones inhibit the DNA binding or the DNA relegation step of eukaryotic topoisomerase-I. J Biol Chem 1996;271:2262-2270.
Huesken BCP, Dejong J, Beekman B, Onderwater RCA. Flavonoids as cardio protective agents. Cancer Chemother Pharmacol 1995;37:55-62.
Izzo AA, Dicarlo G, Mascolo N, Capasso F et al. Antiulcer effect of flavonoids. Role of endogenous PAF. Phytoterapy Res 1991;8:179-181.
Raj KJ, Shalini K. Flavonoids. A review of biological activities. Indian Drugs 1999;36:668-678.
Nishino C, Enoki N, Tawata S, Mori A et al. Tea flavonoids and microbial disease: A review. Agric Biol Chem 1987;51:139-145.
Arai Y, Watanabe S, Kimira M. Dietary intake of flavonols, flavones and isoflavones by Japanesee women and the inverse correlation between quercetin, liquiritigenin intake and plasma LDL cholesterol concentration. J Nutr 2000;130:2243-2250.
Ruikc. Advances in pharmacological studies of silymarin. Mem Inst Oswaldo Cruz 1991;86:79-85.
Pradhan SC, Girish C. Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. Indian J Med Res 2006;124(5):491-504.
De Lira Mota KS, Nunes Dias GE, Ferreira Pinto ME, Ferreira ÂL et al. Flavonoids with gastroprotective activity. Molecules 2009;14:979-1012.
Suzuki Y, Ishihara M, Segami T, Ito M. Anti-ulcer effects of antioxi dants, quercetin, alpha-tocopherol, nifedipine and tetracycline in rats. Jpn J Pharmacol 1998;78(4):435-441.
Pharm TK, Vinh PT, Nong HD, Nguyen DK. Flavonoids as antimicrobial agents. Tap chi Duouc Hoc 1993;6:14-21.
Nishino C, Enoki N, Tawata S, Mori A et al. Tea flavonoids and microbial disease: A review. Agric Biol Chem 1987;51:139-145.
Kujumgier A, Tsvetkova J, Serkedjieva Y, Bankova V et al. Antibacterial, antifungal and antiviral activity of propolis of different geographic origin. J Ethno Pharmacol 1999;64:235-240.
Sato M, Fujiwara S, Tsuchiya H, Fujii T et al. Role of flavonoids in microbial diseases. J Ethnopharmacol 1996;54:171-178.
Ghazal SA, Abuzarqua M, Mahansneh AM. Effect of plant flavonoids on immune and inflammatory cell function. Phytother Res 1992;6:265-271.
Sanabria GA, Ospina SA, Ceronn JA, Raman MJ. Quercetin and related bioflavonoids: A review. Rev Colomb Cienc Quim Farm 1991;19:44-51.
Galati EM, Monforte MT, Kirjavainen S, Forestieri AM et al. Biological effects of hesperidin, a citrus flavonoid. (Note I): antiinflammatory and analgesic activity. Farmacol 1994;40(11):709–712.
Loscalzo LM, Wasowski C, Paladini AC et al. Marder. Opioid receptors are involved in the sedative and antinociceptive effects of hesperidin as well as in its potentiation with benzodiazepines. Eur J Pharmacol. 2000;580(3):306–313.
K Raj Narayana M, Sripal Reddy MR, Chaluvadi DR. Krishna. Bioflavonoids classification, pharmacological, biochemical effects and therapeutic potential. Indian J Pharmacol 2001;33:2-16.
Paul P, Ritra J, Ritva S, Mackku H et al. Dietary flavonoids and risk of lung cancer and other malignant neoplasms. Am J Epidemiol 1997;146:223-230.
Matsuzaki K, Yamakuni T, Hashimoto M, Haque A et al. Nobiletin restoring β-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer’s disease model rats. Neurosci Lett 2006;400(3):230-234.
Nagase H, Omae N, Omori A, Nakagawasai O et al. Nobiletin and its related flavonoids with CRE-dependent transcription-stimulating and neuritegenic activities. Biochem. Biophys Res Commun 2005;4(337):1330-1336.
Matsuzaki K, Miyazaki K, Sakai S, Yawo H et al. Nobiletin, a citrus flavonoid with neurotrophic action, augments protein kinasa A-mediated phosphorylation of the AMPA receptor subunit, GluR1, and the postsynaptic receptor response to glutamate in murine hippocampus. Eur J Pharm 2008;578:194-200.
Nakajima A, Yamakuni T, Haraguchi M, Omae N et al. Nobiletin, a citrus flavonoid that improves memory impairment, rescues bulbectomy- induced cholinergic neurodegeneration in mice. J Pharmacol Sci 2007;105:122-126.
Wolfman C, Viola H, Marder M, Wasowski C et al. Anxioselective properties of 6,3’-dinitroflavone, a high-affinity benzodiazepine receptor ligand. Eur J Pharm 1996;318:23–30.
Olsen WR, Siergart W. International Union of Pharmacology. LXX. Subtypes of γ-Aminobutyric acidA receptors: Classification, pharmacology and function. Update. Pharmcol Rev 2008;60(3):243-260.
Goutman JD, Waxemberg MD, Doñate-Oliver F, Pomata PE et al. Flavonoid modulation of ionic currents mediated by GABAA and receptors GABAC receptors. Eur J Pharmacol 2003;461:79-87.
Marder M, Viola H, Wasowski C, Fernandez S et al. 6-Methylapigenin and hesperidin: new valeriana flavonoids with activity on the CNS. Pharmacol Biochem Behav 2003;75:537–545.
Martínez MC, Fernandez SP, Loscalzo LL, Wasowski C et al. Hesperidin, a flavonoid glycoside with sedative effect, decreases brain Perk1/2 levels in mice. Pharmacol Biochem Behav 2009;92:291-296.
Hanrahan RJ, Chebib M, Johnston ARG. Flavonoid modulation of GABAA receptors. Brit J Pharmacol 2011;163:234-245.
Hui KM, Huen MS, Wang HY, Zheng H et al. Anxiolytic effect of wogonin, a benzodiazepine receptor ligand isolated from Scutellaria baicalensis Georgi. Biochem Pharm 2002;64:1415-1424.
Coleta M, Graca Campos M, Cotrim MD, de Lima TCM et al. Assessment of luteolin (3’, 4’,5, 7-tetrahydroxyflavone)neuropharmacological activity. Behav Brain Research 2008;189:75–82.
Ognibene E, Bovicelli P, Adriani W, Saso L et al.. Behavioral effects of 6-bromoflavanone and 5-methoxy-6, 8-dibromoflavanone as anxiolytic compounds. Prog Neuropsychopharmacol Biol Psych 2008;32:128–134.
Nassiri-Asl M, Shariati-Rad S, Zamansoltani F. Anticonvulsive effects of intracerebroventricular administration of rutin in rats. Prog Neuropsychopharmacol Biol Psych 2008;32:989–993.
Rasilingam D, Duraisamy S, Subramanian R. Anticonvulsant activity of bioflavonoid gossypin. J Bangladesh Pharmacol Soc 2009;4:51-54.
Martínez MC, Fernandez SP, Loscalzo LM, Wasowski C et al. Hesperidin, a flavonoid glycoside with sedative effect, decreases brain pERK1/2 levels in mice. Pharmacol Biochem Behav 2009;92:291–296.
Wang LE, Cui XY, Cui SY, Cao JX et al. Potentiating effect of spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, on pentobarbital- induced sleep may be related to postsynaptic 5-HT1A receptors. Phytomedicine 2010;17:404-409.
Meotti FC, Posser T, Missau FC, Pizzolatti MG et al. Involvement of p38MAPK on the antinociceptive action of myricitrin in mice. Biochem Pharmacol 2007;74(6):924–931.
Kawabata K, Kawai Y, Tera J. Suppressive effect of quercetin on acute stress-induced hypothalamic-pituitary-adrenal axis response in Wistar rats. J Nutr Biochem 2010;21:374–380.
Li-Tao Y, Jian-Mei L, Yu-Cheng L, Ying P et al. Antidepressant-like behavioral andneurochemical effects of the citrus-associated chemical apigenin. Life Sci 2008;82:741–751.
Nagase H, Yamakuni T, Matsuzaki K, Maruyama Y. Mechanism of neurotrophic action of nobiletin in PC12D cells. Biochemistry 2005;44:13683–13691.
Lee H, Kim YO, Kim H, Kim SY. Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia. FASEB J 2003;17:1943–1944.
Li R, Huang YG, Fang D, Le WD. (-)-Epigallocatechin gallate inhibits lipopolysaccharide-induced microglial activation and protects against inflammation-mediated dopaminergic neuronal injury. J Neurosc Res 2004;78:723–731.
Sharma V, Mishra M, Ghosh S, Tewari R et al. Modulation of interleukin- 1β mediated inflammatory response in human astrocytes by flavonoids: Implications in neuroprotection. Brain Res Bull 2007;73: 55–63.
Muthiah NS, Viswanathan S, Thirugnanasambantham P, Reddy MK et al. Antiinflammatory activity of flavone and its mono-methoxy derivatives. A structure activity study. Indian J Pharmacol Sci 1993;55:180–183.
Lou H, Fan P, Pérez RG, Lou H. Neuroprotective effects of linarin through activation of the PI3/Akt pathway in amiloid-β- induced neuronal cell death. Bior Med Chem 2011;19:4021-4027.
Schroeter H, Boyd C, Spencer JPE, Williams RJ et al. MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide. Neurobiol Aging 2002;23:861–880.
Richetti SK, Blank M, Capiotti KM, Piato AL et al. Quercetin and rutin prevent scopolamine-induced memory impairment in zebrafish. Behav Brain Res 2011;217:10-15.
Huang Q, Xiaohui H, Chourong. Pharmacophore/receptor models for GABAA/BZ subtypes (a1 b3 g2 a5 g2 a6 b3 g2) Via a comprehensive ligand-maping approach. J Med Chem 2000;43:71-95.
Kahberg P. Refinement and evolution of a pharmacophore model for flavone derivates binding to the benzodiazepine site of the GABAA receptor. J Med Chem 2002;45:4188-4201.
Paladini A, Marder M, Medina J. 6-Bromo flavone. A high affinity ligands for the chemical benzodiazepine receptor is a member of family of active flavonoids. Biochem Biophys Res Commun 1996;223:384-389.
Paladini A, Marder M, Medina J. Detection of benzodiazepine receptor ligands in small libraries of flavone derivates sinthetyzed by solution phase combinatorial chemistry. Biochem Biophys Res Commun 1998;249:481-485.
Paladini A, Marder M, Medina J, Viola H et al. Flavonoids and the Central Nervous System: from forgotten factors to potent anxiolytic compounds. J Pharm 1999;51:519-526.
Huang X, Liu T, Gu J, Xiaomin L et al. 3D QSAR Model of flavonoids binding at benzodiazepine site in GABAA Receptors. J Med Chem 2001;44:1883-1891.
Machado D, Bettio L, Cunha M, Santos A et al. Antidepressant-like effect of rutin isolated from the ethanolic extract from Schinus molle L. in mice: Evidence for the involvement of the serotonergic and noradrenergic systems. Eur J Pharmacol 2008;587:163-168.
Williams RJ, Spencer JPE, Rice-Evans C. Flavonoids: Antioxidants or signaling molecules? Free Rad Biol Med 2004;36(7):838-849.
Pérez-Trueba G. Los flavonoides antioxidantes o prooxidantes. Rev Cub Invest Biomed 2003;22(1)1-10.
Spencer JPE. Flavonoids and brain health: multiple effects underpinned by common mechanism. Genes Nutr 2009;4:243-250.