Abstract
Seaweeds present a wide variety of interesting bioactive molecules. In the present work we evaluated the biological activity of the dichloromethane/methanol (2:1) extract (DME) from the brown seaweed Dictyota mertensii against Leishmania amazonensis and its cytotoxic potential on mammalian cells. The extract showed significant inhibitory effect on the growth of promastigote forms (IC50 = 71.60 μg/mL) and low toxicity against mammalian cells (CC50 = 233.10 μg/mL). The DME was also efficient in inhibiting the infection in macrophages, with CC50 of 81.4 μg/mL and significantly decreased the survival of amastigote forms within these cells. The selectivity index showed that DME was more toxic to both promastigote (SI = 3.25) and amastigote (SI = 2.86) forms than to macrophages. Increased NO production was observed in treated macrophages suggesting that besides acting directly on the parasites, the DME also shows an immunomodulatory effect on macrophages. Drastic ultrastructural alterations consistent with loss of viability and cell death were observed in treated parasites. Confocal microscopy and cytometry analyzes showed no significant impairment of plasma membrane integrity, whereas an intense depolarization of mitochondrial membrane could be observed by using propidium iodide and rhodamine 123 staining, respectively. The low toxicity to mammalian cells and the effective activity against promastigotes and amastigotes, point to the use of DME as a promising agent for the treatment of cutaneous leishmaniasis.
Highlights
The metabolic and physiologic ability of marine organisms, especially seaweeds, in dealing with highly complex and hostile environments have resulted in the evolution of a number of secondary metabolic pathways which have high prospects of yielding natural products with unique chemical structures
Our results indicate that the leishmanicidal activity of dichloromethane/methanol (2:1) extract (DME) is associated with mitochondrial depolarization, which leads to the loss of parasite viability and cell death independent of necrosis
In the present study the crude extract of D. mertensii obtained from a dichloromethane/methanol solvent mixture (2:1) (DME) was tested for its leishmanicidal and cytotoxic activities
Summary
The metabolic and physiologic ability of marine organisms, especially seaweeds, in dealing with highly complex and hostile environments have resulted in the evolution of a number of secondary metabolic pathways which have high prospects of yielding natural products with unique chemical structures In this regard, different natural products isolated from marine organisms, mainly from invertebrates and seaweeds, have been reported to possess a broad spectrum of pharmacological properties, such as antiviral [1,2,3], antiprotozoal [4,5,6,7,8], antibacterial [9], antioxidant [10], antifungal [11], cytotoxic [12,13] and antitumoral activities [14,15]. Our results indicate that the leishmanicidal activity of DME is associated with mitochondrial depolarization, which leads to the loss of parasite viability and cell death independent of necrosis
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