Anxiolytic Activity of a Phytochemically Characterized Passiflora incarnata Extract is Mediated via the GABAergic System

Abstract

The purpose of this research was to assess the anxiolytic properties of a phytochemically characterized commercial extract from Passiflora incarnata (PI; Passifloraceae) in the elevated plus maze test in mice. Using an HPLC method, the flavonoids homoorientin, orientin, vitexin, and isovitexin were identified as major compounds. Following oral administration, the extract exerted an anxiolytic effect that was comparable to diazepam (1.5 mg/kg) at a dose of 375 mg/kg and exhibited a U-shaped dose-response curve. In addition, antagonism studies using the GABA_A/benzodiazepine receptor antagonist flumazenil and the 5-HT_1A-receptor antagonist WAY-100 635 were conducted. The active dose was effectively antagonized by flumazenil, but not by WAY-100 635. This study is the first demonstration of the in vivo, GABA-mediated anxiolytic activity of an HPLC- characterized extract of Passiflora incarnata.

Key words

Passiflora incarnata - Passifloraceae - anxiolytic effect - benzodiazepines - elevated plus maze/open field - GABA receptor - 5-HT_1A receptor

References

• 1 Brasseur T, Angenot L. The pharmacognosy of the passion flower.  J Pharm Belg. 1984;  39 15-22
• 2 Passiflorae herba. In: European Pharmacopoeia, 3 rd edition. Strasbourg; 2001
• 3 Nassiri-Asl M, Shariati-Rad S, Zamansoltani F. Anticonvulsant effects of aerial parts of Passiflora incarnata extract in mice: involvement of benzodiazepine and opioid receptors.  BMC Complement Altern Med. 2007;  7 26
• 4 Dhawan K, Kumar S, Sharma A. Antiasthmatic activity of the methanol extract of leaves of Passiflora incarnata. .  Phytother Res. 2003;  17 821-2
• 5 Dhawan K, Sharma A. Antitussive activity of the methanol extract of Passiflora incarnata leaves.  Fitoterapia. 2002;  73 397-9
• 6 de Castro P C, Hoshino A, da Silva J C, Mendes F R. Possible anxiolytic effect of two extracts of Passiflora quadrangularis L. in experimental models.  Phytother Res. 2007;  21 481-4
• 7 Dhawan K, Kumar S, Sharma A. Anxiolytic activity of aerial and underground parts of Passiflora incarnata. .  Fitoterapia. 2001;  72 922-6
• 8 Petry R D, Reginatto F, de-Paris F, Gosmann G, Salgueiro J B, Quevedo J. et al . Comparative pharmacological study of hydroethanol extracts of Passiflora alata and Passiflora edulis leaves.  Phytother Res. 2001;  15 162-4
• 9 Reginatto F H, De-Paris F, Petry R D, Quevedo J, Ortega G G, Gosmann G. et al . Evaluation of anxiolytic activity of spray dried powders of two South Brazilian Passiflora species.  Phytother Res. 2006;  20 348-51
• 10 Akhondzadeh S, Kashani L, Mobaseri M, Hosseini S H, Nikzad S, Khani M. Passionflower in the treatment of opiates withdrawal: a double-blind randomized controlled trial.  J Clin Pharm Ther. 2001;  26 369-73
• 11 Ernst E. Herbal remedies for anxiety – a systematic review of controlled clinical trials.  Phytomedicine. 2006;  13 205-8
• 12 Akhondzadeh S, Naghavi H R, Vazirian M, Shayeganpour A, Rashidi H, Khani M. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam.  J Clin Pharm Ther. 2001;  26 363-7
• 13 Dhawan K, Kumar S, Sharma A. Anti-anxiety studies on extracts of Passiflora incarnata Linneaus.  J Ethnopharmacol. 2001;  78 165-70
• 14 Soulimani R, Younos C, Jarmouni S, Bousta D, Misslin R, Mortier F. Behavioural effects of Passiflora incarnata L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse.  J Ethnopharmacol. 1997;  57 11-20
• 15 Coleta M, Batista M T, Campos M G, Carvalho R, Cotrim M D, Lima T C. et al . Neuropharmacological evaluation of the putative anxiolytic effects of Passiflora edulis Sims, its sub-fractions and flavonoid constituents.  Phytother Res. 2006;  20 1067-73
• 16 Lolli L F, Sato C M, Romanini C V, Villas-Boas Lde B, Santos C A, de Oliveira R M. Possible involvement of GABA A-benzodiazepine receptor in the anxiolytic-like effect induced by Passiflora actinia extracts in mice.  J Ethnopharmacol. 2007;  111 308-14
• 17 Oga S, de Freitas P C, Gomes da Silva A C, Hanada S. Pharmacological trials of crude extract of Passiflora alata. .  Planta Med. 1984;  50 303-6
• 18 Pellow S, Chopin P, File S E, Briley M. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat.  J Neurosci Methods. 1985;  14 149-67
• 19 Kulkarni S K, Dandiya P C. Effects of antidepressant agents on open field behaviour in rats.  Psychopharmacologia. 1973;  33 333-8
• 20 Marchart E, Krenn L, Kopp B. Quantification of the flavonoid glycosides in Passiflora incarnata by capillary electrophoresis.  Planta Med. 2003;  69 452-6
• 21 Dawson G R, Tricklebank M D. Use of the elevated plus maze in the search for novel anxiolytic agents.  Trends Pharmacol Sci. 1995;  16 33-6
• 22 Calabrese E J, Baldwin L A. U-shaped dose-responses in biology, toxicology, and public health.  Annu Rev Public Health. 2001;  22 15-33
• 23 Calabrese E J, Baldwin L A, Holland C D. Hormesis: a highly generalizable and reproducible phenomenon with important implications for risk assessment.  Risk Anal. 1999;  19 261-81
• 24 Medina J H, Paladini A C, Wolfman C, Levi de Stein L, Calvo D, Diaz L E. et al . Chrysin, a naturally occurring monoflavonoid, recognizes benzodiazepine receptors and possesses anticonvulsant properties.  Biochem Pharmacol. 1990;  40 2227-32
• 25 Zanoli P, Avallone R, Baraldi M. Behavioral characterisation of the flavonoids apigenin and chrysin.  Fitoterapia. 2000;  71 (Suppl 1) S117-23
• 26 Bourin M, Petit-Demouliere B, Dhonnchadha B N, Hascoet M. Animal models of anxiety in mice.  Fundam Clin Pharmacol. 2007;  21 567-74
• 27 Butterweck V, Jurgenliemk G, Nahrstedt A, Winterhoff H. Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test.  Planta Med. 2000;  66 3-6
• 28 Paladini A C, Marder M, Viola H, Wolfman C, Wasowski C, Medina J H. Flavonoids and the central nervous system: from forgotten factors to potent anxiolytic compounds.  J Pharm Pharmacol. 1999;  51 519-26
• 29 Speroni E, Minghetti A. Neuropharmacological activity of extracts from Passiflora incarnata. .  Planta Med. 1988;  54 488-91
• 30 Wolfensohn S, Lloyd M. Handbook of laboratory animal management and welfare. Oxford; Oxford University Press 1994