title: Antileishmanial activity of essential oil and 6,7-dehydroroyleanone isolated from Tetradenia riparia.
abstract: Tetradenia riparia plant is used as a traditional medicine in Africa for the treatment of inflammatory and infectious diseases as like parasitic. Therapy for leishmaniasis caused by Leishmania (Leishmania) amazonensis specie often fails, and the conventional drugs are toxic, expensive, require a long period of treatment, and adverse effects are common. The alternative therapies using natural products are inexpensive and have few or any adverse reaction. These reasons are sufficient to investigate the new natural therapeutic for leishmaniasis. We evaluated the potential of the essential oil (TrEO) and 6,7-dehydroroyleanone (TrROY) isolated from T. riparia on L. (L.) amazonensis promastigote and amastigote forms, cytotoxicity on human erythrocytes and murine macrophages, nitric production and inducible nitric oxide synthase (iNOS) mRNA expression. TrEO was the most effective to promote the Leishmania promastigote death. After 72 h incubation, the lethal dose of TrEO and TrROY that promoted 50% Leishmania death (LD50) were 0.8 μg/mL and 3 μg/mL, respectively. TrEO and TrROY were not cytotoxic to human erythrocytes, but TrROY was toxic to murine macrophages resulting in a low selectivity index. The transmission electronic microscopy showed that TrEO (0.03 μg/mL) was able to modify the promastigote ultrastructures suggesting autophagy as chromatin condensation, blebbing, membranous profiles and nuclear fragmentation. Infected-macrophages treated with TrEO (0.03 μg/mL) or TrROY (10 μg/mL) had an infection index decreased in 65 and 48%. TrEO did not induce iNOS mRNA expression or nitrite production in macrophages infected with Leishmania. TrROY and mainly TrEO promoted the Leishmania death, and TrROY showed loss toxicity to erythrocytes cells. Other compounds derived from T. riparia and the essential oil could be explored to develop a new alternative treatment for leishmaniasis.
authors.affiliation: Laboratório de Imunologia Clínica da Universidade Estadual de Maringá, Maringá, Paraná, Brazil. Electronic address: bel_galhardo@yahoo.com.br.
authors.forename: Izabel Galhardo
authors.initials: IG
authors.lastname: Demarchi
authors.affiliation: Laboratório de Imunologia Clínica da Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
authors.forename: Mateus Vailant
authors.initials: MV
authors.lastname: Thomazella
authors.affiliation: Laboratório de Imunologia Clínica da Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: de Souza Terron
authors.affiliation: Laboratório de Imunologia Clínica da Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
authors.forename: Lilian
authors.initials: L
authors.lastname: Lopes
authors.affiliation: Laboratório de Química de Produtos Naturais da Universidade Paranaense, Umuarama, Paraná, Brazil.
authors.forename: Zilda Cristiani
authors.initials: ZC
authors.lastname: Gazim
authors.affiliation: Departamento de Farmácia e Farmacologia da Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
authors.forename: Diógenes Aparício Garcia
authors.initials: DA
authors.lastname: Cortez
authors.affiliation: Laboratório de Biologia Adaptativa, Departamento de Biologia Celular, Universidade Federal do Paraná, Curitiba, Brazil.
authors.forename: Lucélia
authors.initials: L
authors.lastname: Donatti
authors.affiliation: Laboratório de Imunologia Clínica da Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
authors.forename: Sandra Mara Alessi
authors.initials: SM
authors.lastname: Aristides
authors.affiliation: Laboratório de Imunologia Clínica da Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
authors.forename: Thaís Gomes Verzignassi
authors.initials: TG
authors.lastname: Silveira
authors.affiliation: Laboratório de Imunologia Clínica da Universidade Estadual de Maringá, Maringá, Paraná, Brazil.
authors.forename: Maria Valdrinez Campana
authors.initials: MV
authors.lastname: Lonardoni
mesh_terms: D045784:Abietanes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D019686:Lamiaceae / Q000737:chemistry*; D007894:Leishmania mexicana / Q000187:drug effects* / Q000648:ultrastructure; D007928:Lethal Dose 50; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D009822:Oils, Volatile / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D045784:Abietanes; D009822:Oils, Volatile; D010936:Plant Extracts; D012333:RNA, Messenger; C043551:6,7-dehydroroyleanone; D052247:Nitric Oxide Synthase Type II
keywords: Antiprotozoal activity; Diterpenoids; Lamiaceae family; Leishmania (Leishmania) amazonensis; Leishmaniasis; Tetradenia riparia