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Synergistic Effect of Lupenone and Caryophyllene Oxide against Trypanosoma cruzi
Acceso Abierto
Chagas disease is a chronic parasitosis caused by the -agellate protozoan Trypanosoma cruzi, which is transmitted by an insect vector of the Reduviidae family causing cardiac injury leading to death [1]. *e disease represents an important public health problem in Latin America, with an estimated 10 million people infected and 25 million people under risk of infection [2]. At present, there is no satisfactory chemotherapy for the disease also known as American trypanosomiasis; the drugs currently used, which include nifurtimox, benznidazole, and allopurinol, are toxic, have severe side e,ects, and are e,ective mainly in the acute phase, while their activity in the chronic phase of the disease is low and controversial [3–5]. Because of this, the WHO has emphasized the need to develop new and better trypanocidal drugs with none or limited side e,ects [6]. A strategy for the development of new and more e.cient pharmaceuticals is to evaluate the synergism between two or more products as part of a treatment of combined therapy. O/en, the therapeutic activity of a combination of drugs is greater than the activity of each product when administrated separately; additionally, synergism can improve the e.ciency of the treatment, broaden its spectrum of action, limit the development of resistant strains, and reduce its duration and toxicity [7, 8]. *ese arguments, supported by the recent recommendation by the WHO that oral artemisininbased monotherapies are withdrawn from the market and replaced with artemisinin-based combination therapies for the treatment of malaria [9], emphasize the importance of considering combined therapies as an alternative for the treatment of protozoan diseases. We have recently carried out a study of native plants of the Yucatan Peninsula and reported the presence of trypanocidal ´ activity in the leaf extract of Serjania yucatanensis [10]. *e bioassay-guided puri+cation of the bioactive crude extract resulted in the identi+cation of a 1:1 mixture of terpenoids, lupenone (a triterpene) and caryophyllene oxide (an oxygenated sesquiterpene), as that responsible for the originally detected trypanocidal activity; the mixture also proved to 2 Evidence-Based Complementary and Alternative Medicine inhibit the egress of trypomastigotes from infected Vero cells without being cytotoxic [11]. We wish to report herein on the synergism of a 1: 4 mixture of lupenone and caryophyllene oxide when tested in vitro fo
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