Contents lists available at ScienceDirect Biomedicine & Pharmacotherapy journal homepage: www.elsevier.com/locate/biopha Original article Licochalcone A induces morphological and biochemical alterations in Schistosoma mansoni adult worms Ritieres Lovo Souza a , Ubirajara Oliveira Gonçalves a , Fernanda Rafacho Badoco a , Lucas de Souza Galvão a , Raquel Alves dos Santos a , Paulo Henrique Dias de Carvalho b , Lara Soares Aleixo de Carvalho b , Ademar Alves da Silva Filho b , Rodrigo Cássio Sola Veneziani a , Vanderlei Rodrigues c , Sérgio Ricardo Ambrósio a, ⁎ , Lizandra Guidi Magalhães a, ⁎ a Research Group on Natural Products, Center for Research in Sciences and Technology, University of Franca, Franca, SP, Brazil b Department of Pharmaceutical Sciences, College of Pharmacy, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil c Department of Biochemical and Immunology, College of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil ARTICLE INFO Keywords: Chalcone Licochalcone A Schistosoma mansoni Schistosomicidal drug ABSTRACT This paper is the first report on the in vitro effects of licochalcone A, a chalcone isolated from Glycyrrhiza inflate Batalin (Leguminosae), on Schistosoma mansoni adult worms. In vitro, licochalcone A afforded lethal con- centrations for 50% of parasites (LC 50 ) of 9.12 ± 1.1 and 9.52 ± 0.9 μM against female and male adult worms, respectively, at 24 h. Additionally, the compound reduced the total number of S. mansoni eggs and affected the development of eggs produced by S. mansoni adult worms. Together, the results achieved after 24 h showed that licochalcone A was 55.7- and 53.3-fold more toxic to S. mansoni female and male adult worms than to Chinese hamster ovary fibroblasts cells, respectively. Treatment with licochalcone A elicited drastic changes in the te- gument of S. mansoni adult worms, as well as mitochondrial alteration and chromatin condensation. Licochalcone A also increased the superoxide anion level and decreased the superoxide dismutase activity in S. mansoni adult worms. Overall, our results indicated that licochalcone A displays in vitro schistosomicidal activity. This effect may result from increased production of reactive oxygen species (ROS) induced by the action of licochalcone A. The resulting ROS could act on the S. mansoni tegument and membranes and help induce the death of S. mansoni adult worms. 1. Introduction Schistosomiasis is a neglected tropical disease (NTD) caused by trematode worms of the genus Schistosoma. This disease affects more than 200 million people worldwide, and the number of people at risk of infection is estimated to be between 600 and 779 million [1,2]. It causes over 300,000 deaths annually and leads to the loss of 1.53 million active lives per year due to disability of adjusted life (DALYs) [3]. Since the introduction of praziquantel (PZQ) in 1980, patients with schistosomiasis have been treated with this drug [2]. PZQ is successful for many reasons: it is effective against all Schistosoma species, it is safe, it is largely available, it treats the disease in a single oral dose, it is inexpensive, and it dismisses the need for direct medical supervision [2]. However, there are also drawbacks to the use of PZQ, such as the emergence of Schistosoma strains that are less sensitive to PZQ, the low efficacy of PZQ in juvenile worms (between 7 and 28 days old), and PZQ’s failure to prevent reinfection [4,5]. In addition, PZQ tablets are large and taste bitter, and there is no readily available pediatric for- mulation [6]. Reliance on a single antischistosomal drug is alarming and attracted the attention of the scientific community, who are searching for a lead compound to develop into a novel, inexpensive, safe, and effective drug against schistosomiasis [7,8]. Natural products, such as plants, are a rich and promising source for the discovery of novel biologically active compounds against neglected tropical diseases (NTD), including schis- tosomiasis [6,9,10]. Among the several classes of secondary metabolites derived from plants, chalcones are a group of plant-derived phenolic compounds belonging to the flavonoids family that possess a wide variety of cyto- protective and modulatory functions. This may have therapeutic po- tential for multiple diseases [11]. Licochalcone A is a characteristic http://dx.doi.org/10.1016/j.biopha.2017.09.128 Received 8 August 2017; Received in revised form 22 September 2017; Accepted 24 September 2017 ⁎ Corresponding authors at: Laboratório de Pesquisa em Parasitologia, Núcleo de Pesquisa em Ciências Exatas e Tecnológicas, Universidade de Franca, Av. Dr. Armando Salles de Oliveira, 201, CEP 14404-600, Franca, SP, Brazil. E-mail addresses: sergio.ambrosio@unifran.edu.br (S.R. Ambrósio), lizandra.magalhaes@unifran.edu.br (L.G. Magalhães). Biomedicine & Pharmacotherapy 96 (2017) 64–71 0753-3322/ © 2017 Elsevier Masson SAS. All rights reserved. MARK