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.
Cutaneous leishmaniasis usually presents therapeutic resistance to antimonials, and the existing therapies for leishmaniasis have many adverse effects and toxicity. Natural products may be regarded as possible candidates for alternative leishmaniasis treatment. The plant Tetradenia riparia has shown promise for the treatment of infectious diseases in folk medicine. We evaluated the antileishmanial activity of an essential oil from T. riparia (TrEO) and the modulatory effects of TrEO on cytokine modulation by peritoneal fluid cells that were infected with L. (L.) amazonensis. Peritoneal fluid cells were infected with Leishmania and incubated with TrEO (30 ng/mL) for 3, 6, and 24 h. Cytokines were screened using semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) and flow cytometry. Antileishmanial activity was evaluated at 24 h by microscopic counting and quantitative PCR (qPCR). TrEO treatment induced the death of 50% of Leishmania amastigotes (indicated by microscopic counting) and 91% of the parasite load (indicated by qPCR). TrEO inhibited some of the most critical cytokines for parasite growth and the establishment of infection, including granulocyte-macrophage colony-stimulating factor, interleukin-4 (IL-4), IL-10, and tumour necrosis factor. The parasite inhibited interferon-γ and IL-12, and TrEO blocked this inhibition, indicating that these cytokines are critical for activating mechanisms associated with the death and elimination of the parasite. These results suggest that TrEO may be an alternative leishmaniasis therapy when considering its antileishmanial and immunomodulatory activity.
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