title: Leishmanicidal effect of Spiranthera odoratíssima (Rutaceae) and its isolated alkaloid skimmianine occurs by a nitric oxide dependent mechanism.
abstract: Leishmaniasis is one of the neglected diseases. High cost, systemic toxicity, and diminished efficacy due to development of resistance by the parasites has a negative impact on the current treatment options. Thus, the search for a new, effective and safer anti-leishmanial drug becomes of paramount importance. Compounds derived from natural products may be a better and cheaper source in this regard. This study evaluated the in vitro anti-leishmanial activity of Spiranthera odoratíssima (Rutaceae) fractions and isolated compounds, using promastigote and amastigote forms of different Leishmania species. J774 A.1 macrophage was used as the parasite host cell for the in vitro assays. Evaluations of cytoxicity, nitric oxide (NO), interleukin-10 and in silico analysis were carried out. In vitro experiments showed that the fruit hexanic fraction (Fhf) and its alkaloid skimmianine (Skm) have a significant (P<0·001) effect against L. braziliensis. This anti-L. braziliensis activity of Fhf and Skm was due to increased production of NO and attenuation of IL-10 production in the macrophages at concentrations ranging from 1·6 to 40·0 μg/ml. The in silico assay demonstrated significant interaction between Skm and amino acid residues of NOS2. Skm is thus a promising drug candidate for L. braziliensis due to its potent immunomodulatory activity.
authors.affiliation: Laboratório de Imunofarmacologia, Laboratório de Tecnologia Farmacêutica- LTF, Departamento de Fisiologia e Patologia, Universidade Federal da Paraíba - UFPB, Campus I, João Pessoa, Paraíba, Brazil.
authors.forename: Rogerio Alexandre Nunes
authors.initials: RA
authors.lastname: Dos Santos
authors.forename: João
authors.initials: J
authors.lastname: Batista
authors.forename: Suellen Iara Guirra
authors.initials: SI
authors.lastname: Rosa
authors.forename: Heron Fernandes
authors.initials: HF
authors.lastname: Torquato
authors.forename: Carmen Lúcia
authors.initials: CL
authors.lastname: Bassi
authors.forename: Tereza Auxiliadora Nascimento
authors.initials: TA
authors.lastname: Ribeiro
authors.forename: Paulo Teixeira
authors.initials: PT
authors.lastname: De Sousa
authors.forename: Angela Márcia Selhorst E Silva
authors.initials: AM
authors.lastname: Bessera
authors.forename: Cor Jesus Fernandes
authors.initials: CJ
authors.lastname: Fontes
authors.forename: Luiz Everson
authors.initials: LE
authors.lastname: Da Silva
authors.forename: Márcia Regina
authors.initials: MR
authors.lastname: Piuvezam
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D005638:Fruit / Q000737:chemistry; D006586:Hexanes / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007892:Leishmania braziliensis / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology; D008018:Life Cycle Stages / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008958:Models, Molecular; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000737:chemistry / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D027821:Rutaceae / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D000981:Antiprotozoal Agents; D006586:Hexanes; D010936:Plant Extracts; D011804:Quinolines; D016753:Interleukin-10; D009569:Nitric Oxide; C035932:skimmianine; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II