The consumption of flavonoid-rich foods, in particular fruits and vegetables, has been epidemiologically associated with a reduced risk of heart disease, neurodegenerative disease, cancer and other chronic diseases. Flavonoid glycosides, the main class of flavonoids, have been shown to exert CNS-mediated activities, particularly as sedative-hypnotics, analgesics or both, nevertheless no studies have evaluated these agents in anxiety. This study assessed the potential anxiolytic effect of three flavonoid glycosides, myrcitrin, naringin and gossypin, in the elevated plus maze test (EPM). Myricitrin (1 mg/kg) was effective on the EPM showing a clear anxiolytic effect with no signs of sedation. However, higher doses showed possible sedative and myorelaxation effects. Gossypin and naringin both shared a similar profile, with low doses (1 mg/kg) inducing a robust anxiolytic effect which diminished with increasing doses of the flavonoids. Higher doses of these two flavonoids showed a dramatic increase in the open arm exploration accompanied by a decrease in locomotor activity. Hence, naringin (30 mg/kg) and gossypin (30 mg/kg) induce both anxiolytic and sedative effects. These results suggest that flavonoid glycosides have the potential to exert a range of CNS-mediated biological activities.
Naringin Gossypin Myricitrin Flavone Flavonoid glycosides Elevated plus maze
This is a preview of subscription content, log in to check access
The authors are indebted to Dr. Alejandro A. Paladini (INGEBI, Buenos Aires, Argentina) for designing the behavioural apparatus. This research was supported by a grant from the National Health and Medical Research Council (NH&MRC) of Australia.
Katsenis K (2005) Micronized purified flavonoid fraction (MPFF): a review of its pharmacological effects, therapeutic efficacy and benefits in the management of chronic venous insufficiency. Curr Vasc Pharmacol 3:1–9. doi:10.2174/1570161052773870PubMedCrossRefGoogle Scholar
Meotti FC, Luiz AP, Pizzolatti MG et al (2006) Analysis of the antinociceptive effect of the flavonoid myricitrin: evidence for a role of the l-arginine-nitric oxide and protein kinase C pathways. J Pharmacol Exp Ther 316:789–796. doi:10.1124/jpet.105.092825PubMedCrossRefGoogle Scholar
Martínez-Vázquez M, Ramírez Apan TO, Lastra AL et al (1998) A comparative study of the analgesic and anti-inflammatory activities of pectolinarin isolated from Cirsium subcoriaceum and linarin isolated from Buddelia cordata. Planta Med 64:134–137. doi:10.1055/s-2006-957390PubMedCrossRefGoogle Scholar
Loscalzo LM, Wasowski C, Paladini AC et al (2008) Opioid receptors are involved in the sedative and antinociceptive effects of hesperidin as well as in its potentiation with benzodiazepines. Eur J Pharmacol 580:306–313. doi:10.1016/j.ejphar.2007.11.011PubMedCrossRefGoogle Scholar
Kissin I, Brown PT, Bradley EL Jr (1990) Sedative and hypnotic midazolam-morphine interactions in rats. Anesth Analg 71:137–143PubMedGoogle Scholar
Agmo A, Galvan A, Heredia A et al (1995) Naloxone blocks the antianxiety but not the motor effects of benzodiazepines and pentobarbital: experimental studies and literature review. Psychopharmacology (Berl) 120:186–194. doi:10.1007/BF02246192CrossRefGoogle Scholar
Filliol D, Ghozland S, Chluba J et al (2000) Mice deficient for delta- and mu-opioid receptors exhibit opposing alterations of emotional responses. Nat Genet 25:195–200. doi:10.1038/76061PubMedCrossRefGoogle Scholar
Kobayashi T, Ikeda K, Ichikawa T et al (1995) Molecular cloning of a mouse G-protein-activated K+ channel (mGIRK1) and distinct distributions of three GIRK (GIRK1, 2 and 3) mRNAs in mouse brain. Biochem Biophys Res Commun 208:1166–1173. doi:10.1006/bbrc.1995.1456PubMedCrossRefGoogle Scholar
Guasti L, Cilia E, Crociani O et al (2005) Expression pattern of the ether-a-go-go-related (ERG) family proteins in the adult mouse central nervous system: evidence for coassembly of different subunits. J Comp Neurol 491:157–174. doi:10.1002/cne.20721PubMedCrossRefGoogle Scholar
Chu CP-Y (2006) Three Pharmacological studies on nicotinic acetylcholine receptors: β-amyloid peptides, flavonoids and α-conotoxins. Ph. D Thesis, University of Sydney, SydneyGoogle Scholar
Tsai TH (2002) Determination of naringin in rat blood, brain, liver, and bile using microdialysis and its interaction with cyclosporin a, a p-glycoprotein modulator. J Agric Food Chem 50:6669–6674. doi:10.1021/jf020603pPubMedCrossRefGoogle Scholar
Peng HW, Cheng FC, Huang YT et al (1998) Determination of naringenin and its glucuronide conjugate in rat plasma and brain tissue by high-performance liquid chromatography. J Chromatogr A 714:369–374Google Scholar