ANTIVIRAL EFFECT OF CAPPARIS SPINOSA 313 Copyright © 2007 John Wiley & Sons, Ltd. Phytother. Res. 22, 313–317 (2008) DOI: 10.1002/ptr Copyright © 2007 John Wiley & Sons, Ltd. PHYTOTHERAPY RESEARCH Phytother. Res. 22, 313–317 (2008) Published online 4 December 2007 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/ptr.2313 Antiviral and Immunomodulatory Effect of a Lyophilized Extract of Capparis spinosa L. Buds A. Arena 1 , G. Bisignano 2 , B. Pavone 1 , A. Tomaino 2 , F. P. Bonina 3 , A. Saija 2 *, M. Cristani 2 , M. D’Arrigo 2 and D. Trombetta 2 1 Department of Surgical Science, Unit of Microbiology, University of Messina 2 Department Farmaco-Biologico, University of Messina 3 Department of Pharmaceutical Science, University of Catania, Italy Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are common human pathogens that in particular cases can also cause severe problems especially in immunodeficient patients. The present paper reports the antiviral and immunomodulatory properties of a methanolic extract of C. spinosa buds (CAP), rich in flavonoids, including several quercetin and kaempferol glycosides. In particular we have inves- tigated whether the in vitro exposure of human peripheral blood mononuclear cells (PBMCs) to CAP might inhibit the replication of HSV-2 and modulate the induction kinetics of IL-12, TNF- α α α IFN- γ γ γ. Our findings have shown that CAP treatment interferes with HSV-2 replication in PBMCs inhibiting the extracellular virus release upregulating their production of IL-12, IFN- γ γ γ and TNF- α α α . One could speculate that CAP may contrib- ute in improving immune surveillance of PBMCs toward virus infection by up-regulating expression of pecu- liar proinflammatory cytokines; it should thus be successfully employed for treatment of HSV-2 infections in immunocompromised hosts. Copyright © 2007 John Wiley & Sons, Ltd. Keywords: Capper spinosa buds, Herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), antiviral, immunomodulatory, peripheral blood mononuclear cells (PBMCs). Received 31 January 2007 Revised 29 June 2007 Accepted 10 July 2007 * Correspondence to: Professor Antonella Saija, Department Farmaco- Biologico, School of Pharmacy, University of Messina, Contrada Annunziata, 98168 Messina, Italy. E-mail: saija@pharma.unime.it INTRODUCTION Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are common human pathogens that cause localized skin infections of mucosal epithelia in genitals, oral cavity, pharynx, oesophagus and eyes; however HSV infections are latent and can be periodi- cally reactivated (Simmons, 2002). In particular cases HSV can also cause severe problems. In fact the virus can produce serious infections of the central nervous system, and HSV infections may be fatal in immunode- ficient patients; furthermore the immediate-early genes of HSV-1 can stimulate the activation of genes belong- ing to different viruses such as human immunodeficiency virus, varicella-zoster virus and papillomavirus. Efficient elimination of viruses relies on the ability of the infected host to mount a proinflammatory immune response and develop a Th-1 type immunity (Lucey et al., 1996; Carr and Tomanek, 2006). This response is characterized by activation of monocytes/macrophages, cytotoxic T-lymphocytes and production of proinflam- matory cytokines and chemokines, including interferons (IFN), tumor necrosis factor-α (TNF-α) and interleukins (IL). Helper T lymphocytes (Th) may be divided into two functional subclasses, Th-1 and Th-2 cells, based upon the cytokines that they produce and their effects on cell mediated and humoral immunity. Th-1 cells produce IL-2, IFNγ and IL-12, enhance cell-mediated immunity and inhibit cell-mediated immunological activities. Th-1 cells drive the type-1 pathway (cellular immunity) to fight viruses and other intracellular patho- gens and eliminate cancerous cells. Primary biological functions of Th-1 derived cytokines include antiviral and anticancer effects. Th-2 cells produce IL-4, IL-5, IL-6 and IL-10 and upregulate humoral immunity. Th- 2 cells drive the type-2 pathway (humoral immunity) and upregulate antibody production to fight extracellular organisms. In addition, Th1 and Th2 derived cytokines cross-regulate each other in various clinical conditions (Kidd, 2003). Due to the evident need for effective antiviral therapy, in recent years a large number of naturally occurring compounds with antiviral and immunomodulatory com- ponents have been investigated in the attempt to develop new safe agent able to inhibit specifically viral functions and/or to influence the response of the host to viruses (Armaka et al., 1999; Arena et al., 2006). Capparis spinosa L. (family Capparidaceae) is a plant from the dry regions in west or central Asia and widely grown particularly in the Mediterranean basin. From ancient times, the floral buttons of C. spinosa (capers) were employed as a flavouring in cooking and are also used in traditional medicine for their diuretic, anti- hypertensive, poultice and tonic properties (Baytop, 1984; Çali8 et al., 1999). Previous chemical studies on C. spinosa have shown the presence of alkaloids, lipids, polyphenols, flavonoids, indole and aliphatic