Antianaphylactic Properties of 7-Epiclusianone, a Tetraprenylated Benzophenone Isolated from Garcinia brasiliensis

Abstract

Prior studies have emphasized the anti-inflammatory and antioxidant properties of polyisoprenylated benzophenone derivatives, but their putative effect on allergic conditions has not yet been addressed. In the current study, the naturally occurring 7-epiclusianone, isolated from Garcinia brasiliensis, was investigated to check its effectiveness on allergen-evoked intestinal spasm. The standard antiallergic azelastine was used for comparison. We found that 7-epiclusianone and azelastine inhibited antigen-induced contractions of guinea pig ileum with similar IC₅₀ values (2.3 ± 1.1 μM and 3.3 ± 1.2 μM, respectively). A similar blockade of anaphylactic histamine release from the ileum was also noted. In contrast, azelastine was more potent than 7-epiclusianone to prevent spasms induced by histamine (IC₅₀ = 6.3 ± 0.2 nM and 3.7 ± 0.1 μM, respectively). These findings reveal that 7-epiclusianone is clearly active against the anaphylactic response and should be considered as a molecular template in drug discovery for allergic syndromes.

Polyprenylated benzophenones - allergy - anaphylaxis - ileum contraction - Garcinia brasiliensis - Clusiaceae

• 1 Ampofo S A, Waterman P G. Xanthones and neoflavonoids from two Asian species of Calophyllum .  Phytochemistry. 1986;  25 2617-20.
• 2 Bennett G J, Lee H H. Xanthones from Guttiferae .  Phytochemistry. 1988;  28 967-98.
• 3 Gopalakrishnan G, Banumathi B, Suresh G. Evaluation of the antifungal activity of natural xanthones from Garcinia mangostana and their synthetic derivatives.  J Nat Prod. 1997;  60 519-24.
• 4 Diaz-Carballo D, Seeber S, Strumberg D, Hilger R A. Novel antitumoral compound isolated from Clusia rosea .  Int J Clin Pharmacol Ther. 2003;  41 622-3.
• 5 Hay A EA, Mallet M C, Dumontet S, Litaudon V, Rondeau M, Richomme D P. Antioxidant xanthones from Garcinia vieillardii .  J Nat Prod. 2004;  67 707-9.
• 6 Santos M H, Speziali N L, Nagem T, Oliveira T T. Epiclusianone: a new natural product derivative of bicyclo[3.3.1]nonane-2,4,9-trione.  Acta Crystallogr. 1998;  C54 1990-2.
• 7 Santos M H. Estudo químico dos frutos de Rheedia gardneriana e aplicações biológicas dos seus constituintes [dissertation]. Viçosa; UFV 1996.
• 8 Alves T M, Alves R, Romanha A J, Zani C L, dos Santos M H, Nagem T J. Biological activities of 7-epiclusianone.  J Nat Prod. 1999;  62 369-71.
• 9 Cruz A J, Lemos V S, dos Santos M H, Nagem T J, Cortes S F. Vascular effects of 7-epiclusianone, a prenylated benzophenone from Rheedia gardneriana, on the rat aorta.  Phytomedicine. 2006;  13 442-5.
• 10 Corrêa M P. Dicionário das plantas úteis do Brasil e das exóticas cultivadas, Vol. 1. Rio de Janeiro; Imprensa Nacional 1926.
• 11 Delle Monache G, Botta B. Chemical investigation of the genus Rheedia, IV. Three new xanthones from Rheedia brasiliensis .  J Nat Prod. 1984;  47 620-5.
• 12 Chand N, Diamantis W, Sofia R D. Antagonism of histamine and leukotrienes by azelastine in isolated guinea pig ileum.  Agents Actions. 1986;  19 164-8.
• 13 Foster R W, Okpalugo B I, Small R C. Antagonism of Ca²⁺ and other actions of verapamil in guinea-pig isolated trachealis.  Br J Pharmacol. 1984;  81 499-507.
• 14 Shore P A, Burkhalter A, Cohn VH J r. A method for the fluorometric assay of histamine in tissues.  J Pharmacol Exp Ther. 1959;  127 182-6.
• 15 Balasubramanyam K, Altaf M, Varier R A, Swaminathan V, Ravindran A, Sadhale P P. et al . Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression.  J Biol Chem. 2004;  279 33 716-26.
• 16 Liao C H, Lin J K. Effects of garcinol on free radical generation and NO production in embryonic rat cortical neurons and astrocytes.  Biochem Biophys Res Commun. 2005;  329 1306-14.
• 17 Hong J, Sang S, Park H J, Kwon S J, Suh N, Huang M T. et al . Modulation of arachidonic acid metabolism and nitric oxide synthesis by garcinol and its derivatives.  Carcinogenesis. 2006;  27 278-86.
• 18 Berger W, Hampel F J r, Bernstein J, Shah S, Sacks H, Meltzer E O. Impact of azelastine nasal spray on symptoms and quality of life compared with cetirizine oral tablets in patients with seasonal allergic rhinitis.  Ann Allergy Asthma Immunol. 2006;  97 375-81.
• 19 McTavish D, Sorkin E M. Azelastine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential.  Drugs. 1989;  38 778-800.
• 20 Kakutani C, Ogino S, Ikeda H, Enomoto T. [Comparison of clinical efficacy and cost-quality of antihistamines in early treatment for Japanese cedar pollinosis].  Arerugi. 2006;  55 554-65.
• 21 Horak F, Zieglmayer U P, Zieglmayer R, Kavina A, Marschall K, Munzel U. et al . Azelastine nasal spray and desloratadine tablets in pollen-induced seasonal allergic rhinitis: a pharmacodynamic study of onset of action and efficacy.  Curr Med Res Opin. 2006;  22 151-7.
• 22 Lieberman P L, Settipane R A. Azelastine nasal spray: a review of pharmacology and clinical efficacy in allergic and nonallergic rhinitis.  Allergy Asthma Proc. 2003;  24 95-105.
• 23 Nakamura T, Nishizawa Y, Sato T, Yamato C. Effect of azelastine on the intracellular Ca²⁺ mobilization in guinea pig peritoneal macrophages.  Eur J Pharmacol. 1988;  148 35-41.
• 24 Hazama H, Nakajima T, Hisada T, Hamada E, Omata M, Kurachi Y. Effects of azelastine on membrane currents in tracheal smooth muscle cells isolated from the guinea-pig.  Eur J Pharmacol. 1994;  259 143-50.
• 25 Bolsmann K, Braam U, Eichelberg D, Greven T, Jungbluth C, Schmutzler W. et al . Histamine release from mast cells and monocytes: the effects of azelastine, reproterol and vitamin A-analogues.  Inflamm Res. 1996;  45 S5-6.
• 26 Katayama I, Otoyama K, Yokozeki H, Nishioka K. Effect of mast cell modulators on IgE-mediated murine biphasic cutaneous reactions.  Int Arch Allergy Immunol. 1996;  109 390-7.
• 27 Manabe H, Ohmori K, Tomioka H, Yoshida S. Oxatomide inhibits the release of chemical mediators from human lung tissues and from granulocytes.  Int Arch Allergy Appl Immunol. 1988;  87 91-7.
• 28 Shichijo M, Inagaki N, Nakai N, Kimata M, Nakahata T, Serizawa I. et al . The effects of anti-asthma drugs on mediator release from cultured human mast cells.  Clin Exp Allergy. 1998;  28 1228-36.