Planta Med 2009; 75(4): 295-301
DOI: 10.1055/s-0029-1185306
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Pharmacological Exploration of the Sedative Mechanism of Hesperidin Identified as the Active Principle of Citrus sinensis Flowers

Silvia Laura Guzmán-Gutiérrez1 [*] , Andrés Navarrete1
  • 1Facultad de Química, Departamento de Farmacia. Universidad Nacional Autónoma de México, México
Further Information

Publication History

received Sept. 1, 2008 revised Nov. 10, 1008

accepted Dec. 1, 2008

Publication Date:
13 February 2009 (online)


The infusion of flowers of several species of Citrus genera is used as a sedative to treat insomnia in Mexican traditional medicine. The aims of this study were to investigate the sedative effect of different extracts of flowers of Citrus sinensis (L.) Osbeck (Rutaceae) and describe the pharmacological action mechanism of the sedative active compounds of this plant. The methanol and dichloromethane extracts, obtained from the flowers of Citrus sinensis (L.) Osbeck (Rutaceae), showed a dose-dependent sedative effect in the exploratory cylinder model in mice, with ED50 (i. p.) values of 47.04 ± 12.03 mg/kg and 129.15 ± 21.25 mg/kg, respectively. Hesperidin (ED50 = 11.34 ± 2.48 mg/kg) was identified in the methanol extract as the sedative active principle of this plant. The pre-treatment with atropine (1 mg/kg i. p.), flumazenil (2 mg/kg i. p.), clonidine (0.01 mg/kg i. p.), isoproterenol (0.3 mg/kg i. p.), haloperidol (0.3 mg/kg i. p.), WAY 100 635 (3 mg/kg i. p.), p-chlorophenylalanine (250 mg/kg i. p., twice per day for 2 days), forskolin (3 mg/kg i. p.) and rolipram (0.173 mg/kg i. p.) did not modify the sedative effect of 30 mg/kg hesperidin. However, the sedative effect of this compound was potentiated by yohimbine (1.25 mg/kg i. p.) and buspirone (1 mg/kg i. p.), and reverted by pretreatment with aminophylline (30 mg/kg i. p.), caffeine (30 mg/kg i. p.) and several doses of 1,3-dimethyl-8-phenylxanthine (10, 30 and 54.7 mg/kg i. p.). These results suggest that adenosine receptors might be involved in the sedative action of hesperidin, identified as the active principle of the flowers of Citrus sinensis.


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1 Taken in part from the Ph.D. research work of S. L. Guzmán-Gutiérrez.

Dr. Andrés Navarrete

Facultad de Química, Departamento de Farmacia.
Universidad Nacional Autónoma de México

Ciudad Universitaria

Coyoacán 04510

México D. F.


Phone: + 55 56 22 52 91

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