RESUMEN
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.
Asunto(s)
Antiprotozoarios/farmacología , Leishmania braziliensis/efectos de los fármacos , Leishmaniasis Cutánea/tratamiento farmacológico , Estadios del Ciclo de Vida/efectos de los fármacos , Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacología , Quinolinas/farmacología , Rutaceae/química , Alcaloides/química , Alcaloides/farmacología , Alcaloides/uso terapéutico , Animales , Antiprotozoarios/química , Antiprotozoarios/uso terapéutico , Células Cultivadas , Frutas/química , Hexanos/química , Humanos , Concentración 50 Inhibidora , Interleucina-10/antagonistas & inhibidores , Interleucina-10/biosíntesis , Leishmania braziliensis/citología , Leishmania braziliensis/crecimiento & desarrollo , Leishmania braziliensis/metabolismo , Leishmaniasis Cutánea/parasitología , Macrófagos/metabolismo , Macrófagos/parasitología , Ratones , Modelos Moleculares , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/química , Óxido Nítrico Sintasa de Tipo II/metabolismo , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Quinolinas/química , Quinolinas/uso terapéuticoRESUMEN
Ellagic acid (EA), a plant-derived polyphenol, exhibits antioxidant, anti-inflammatory, and gastroprotective effects. Its gastroprotective mechanisms have not been fully elucidated nor have its effects on chronic ulcer previously been described. Toward these ends, the antiulcer activities of EA were evaluated in acute (ethanol and indomethacin) and chronic (acetic acid) ulcer models in Wistar rats. In this study, oral administration of EA significantly prevented the gastric ulceration caused by ethanol, indomethacin, and acetic acid treatments. Its gastroprotective mechanism in ethanol-induced ulcer were partly due to intensification in the endogenous production of nitric oxide, an antioxidant effect by replenishing depletion of endogenous nonprotein sulfhydryls and attenuation of tumor necrosis factor-α increase, whereas in indomethacin ulcer, it is partly due to a reduction in the plasma level of leukotriene B(4). In acetic acid ulcer, promotion of ulcer-healing effects was partly due to attenuation of the elevated levels of the inflammatory cytokines TNF-α, interferon-γ, and interleukins-4 and -6. These findings suggest that ellagic acid exerts its antiulcer activity by strengthening the defensive factors and attenuating the offensive factors.
