In vitro antileishmanial activity of resveratrol and its hydroxylated analogues against Leishmania major promastigotes and amastigotes.
ABSTRACT Resveratrol, a natural phytoalexin found mainly in grapes, possesses a variety of beneficial activities including anticancer, antimicrobial and antiviral. However, there is no information about its effects on kinetoplastid parasites such as Leishmania. Leishmania is a human pathogen responsible for a spectrum of diseases known as leishmaniases and a significant health problem in many parts of the world. In this study, we investigated effects of resveratrol and its hydroxylated analogues on Leishmania major, a causative agent of zoonotic cutaneous leishmaniasis in the Old World. Resveratrol showed antileishmanial activity against promastigotes in vitro and, more importantly, was effective against intracellular amastigotes, a parasite life stage infectious in humans, as detected in in vitro macrophage assay. The hydroxylated stilbenes tested in this study also showed antileishmanial activity against promastigotes, the most promising being 3,4,4',5'-tetrahydroxy-trans-stilbene. This compound showed excellent antileishmanial activity against extracellular promastigotes in vitro but not intracellular amastigotes. Our results suggest that resveratrol may be useful as a therapeutic agent to treat leishmaniasis and warrant its further assessment in animal models of disease.
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ABSTRACT: Resveratrol, a phenolic antioxidant found in grapes, has been known to mediate various biological activities on the human body. In the present study, we tested the antifungal activity of resveratrol against human pathogenic fungi before carrying out further studies to elucidate the antifungal mechanism(s) of resveratrol. Resveratrol displayed potent antifungal activity against human pathogenic fungi at concentration levels of 10-20 microg/mL. Furthermore, time-kill curve exhibited fungicidal effect of resveratrol on C. albicans, but the compound had no hemolytic activity against human erythrocytes. The destruction of C. albicans cells by resveratrol was confirmed by scanning electron microscopy. These results suggest that resveratrol could be employed as a therapeutic agent to treat fungal infections of humans.Archives of Pharmacal Research 06/2005; 28(5):557-60. · 1.54 Impact Factor
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ABSTRACT: The antileishmanial and immunomodulatory potencies of a total of 67 tannins and structurally related compounds were evaluated in terms of extra- and intra-cellular leishmanicidal effects and macrophage activation for release of nitric oxide (NO), tumour necrosis factor (TNF) and interferon (IFN)-like activities. Their effects on macrophage functions were further assessed by expression analysis (iNOS, IFN-alpha, IFN-gamma, TNF-alpha, IL-1, IL-10, IL-12, IL-18). With few exceptions, e.g., caffeic acid derivatives, these polyphenols revealed little direct toxicity for extracellular promastigote Leishmania donovani or L. major strains. In contrast, many polyphenols appreciably reduced the survival of the intracellular, amastigote parasite form in vitro. Upon activation, e.g., by immune response mediators such as IFN-gamma, macrophages may transform from permissive host to leishmanicidal effector cells. Our data from functional bioassays suggested that the effects of polyphenols on intracellular Leishmania parasites were due to macrophage activation rather than direct antiparasitic activity. Gene expression analyses not only confirmed functional data, they also clearly showed differences in the response of infected macrophages when compared to that of noninfected cells. Conspicuously, infected macrophages showed augmented and prolonged activation of host defense mechanisms, indicating that parasitised macrophages were exquisitely predisposed or "primed" to react to activating molecules such as polyphenols. This promotive effect may be of special benefit, e.g., stimulation of the non-specific immune system selectively at the site of infection and when needed. Although these data provide the basis for an immunological concept of plant polyphenols for their beneficial effects in various infectious conditions, in vivo experiments are essential to prove the therapeutic benefits of polyphenolic immunomodulators.Phytochemistry 10/2005; 66(17):2056-71. · 3.05 Impact Factor
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ABSTRACT: Resveratrol, a phytoalexin, was found to inhibit herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) replication in a dose-dependent, reversible manner. The observed reduction in virus yield was not caused by the direct inactivation of HSV by resveratrol nor inhibition of virus attachment to the cell. The chemical did, however, target an early event in the virus replication cycle since it was most effective when added within 1 h of cell infection, less effective if addition was delayed until 6 h post-infection and not effective if added 9 h post-infection. Resveratrol was also found to delay the cell cycle at S-G2-M interphase, inhibit reactivation of virus from latently-infected neurons and reduce the amount of ICP-4, a major immediate early viral regulatory protein, that is produced when compared to controls. These results suggest that a critical early event in the viral replication cycle, that has a compensatory cellular counterpart, is being adversely affected.Antiviral Research 11/1999; 43(3):145-55. · 3.93 Impact Factor