ORIGINAL ARTICLE Strychnos pseudoquina A. St. Hil.: a Brazilian medicinal plant with promising in vitro antiherpes activity L. Boff 1 , I.T. Silva 1 , D.F. Argenta 1 , L.M. Farias 2 , L.F. Alvarenga 3 , R.M. P adua 3 , F.C. Braga 3 , J.P.V. Leite 2 , J.M. Kratz 1 and C.M.O. Sim~ oes 1 1 Laborat orio de Virologia Aplicada, Programa de P os-graduac ß~ ao em Farm acia, Universidade Federal de Santa Catarina (UFSC), Florian opolis, SC, Brazil 2 Departamento de Bioqu  ımica e Biologia Molecular, Universidade Federal de Vic ßosa (UFV), Vic ßosa, MG, Brazil 3 Departamento de Produtos Farmac^ euticos, Faculdade de Farm acia, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil Keywords HSV-1, HSV-2, quercetin 3-O-methyl ether, standardized extract, strychnobiflavone, Strychnos pseudoquina. Correspondence Cl audia M. O. Sim~ oes, Laborat orio de Virolo- gia Aplicada, Programa de P os-graduac ß~ ao em Farm acia, Universidade Federal de Santa Catarina (UFSC), Campus Trindade, Florian opolis - SC 88040-970, Brazil. E-mail: claudia.simoes@ufsc.br 2016/0915: received 29 April 2016, revised 22 July 2016 and accepted 22 August 2016 doi:10.1111/jam.13279 Abstract Aims: To investigate the anti-HSV and anti-inflammatory effects of a standardized ethyl acetate extract (SEAE) prepared with the stem bark of Strychnos pseudoquina, along with two isolated compounds: quercetin 3-O- methyl ether (3MQ) and strychnobiflavone (SBF). Methods and Results: The mechanisms of action were evaluated by different methodological strategies. SEAE and SBF affected the early stages of viral infection and reduced HSV-1 protein expression. Both flavonoids elicited a concentration-dependent inhibition of monocyte chemoattractant protein-1 (MCP-1), whereas 3MQ reduced the chemokine release more significantly than SBF. Conversely, both compounds stimulated the production of the cytokines TNF-a and IL-1-b in LPS-stimulated cells, especially at the intermediate and the highest tested concentrations. Conclusions: SEAE and SBF interfered with various steps of HSV replication cycle, mainly adsorption, postadsorption and penetration, as well as with b and c viral proteins expression; moreover, a direct inactivation of viral particles was observed. Besides, both flavonoids inhibited MCP-1 selectively, a feature that may be beneficial for the development of new anti-HSV agents. Significance and Impact of the Study: The results indicated that the samples present anti-HSV and anti-inflammatory activities, at different levels, which is an interesting feature since cold and genital sores are accompanied by an inflammation process. Introduction Currently, it is estimated that 60–95% of worldwide adult population is infected with at least one Herpes Simplex Virus (HSV-1 or HSV-2). HSV-1 is generally associated with orofacial infections and HSV-2 with the genitouri- nary tract infections; nevertheless, although this anatomi- cal distinction is no longer as strict as it was. Hence, HSV infections are an important public health problem, especially due to HSV ability to cause acute and recurrent infections as well as to become resistant to commonly used antiherpes drugs. Furthermore, HSV genital infec- tion increases the risk of acquiring human immunodeficiency virus (HIV), which is three times higher in people with HSV-2, indicating that it is a cofac- tor for HIV spreading (Reynolds and Quinn 2005; Roiz- man et al. 2013). HSV-1 and HSV-2 are alphaherpesviruses with double- stranded DNA packed in an icosahedral capsid, which is surrounded by the tegument, and lastly by a lipid envelope containing various glycoproteins. For replication, it is necessary that the viruses adsorb to and penetrate host cells, and express a genes (immediate early phase) that mainly regulate the viral replication, such as ICP27; b genes (early phase) that synthesize and package DNA, such as UL42; and c genes (late phase), which are mostly Journal of Applied Microbiology 121, 1519--1529 © 2016 The Society for Applied Microbiology 1519 Journal of Applied Microbiology ISSN 1364-5072