Immunomodulatory and Antileishmanial Activity of Phenylpropanoid Dimers Isolated from Nectandra leucantha

Abstract

Three phenylpropanoid dimers (1-3) including two new metabolites were isolated from the extract of the twigs of Nectandra leucantha using antileishmanial bioassay-guided fractionation. The in vitro antiparasitic activity of the isolated compounds against Leishmania donovani parasites and mammalian cytotoxicity and immunomodulatory effects were evaluated. Compounds 1-3 were effective against the intracellular amastigotes within macrophages, with IC50 values of 26.7, 17.8, and 101.9 μM, respectively. The mammalian cytotoxicity, given by the 50% cytotoxic concentration (CC50), was evaluated against peritoneal macrophages. Compounds 1 and 3 were not toxic up to 290 μM, whereas compound 2 demonstrated a CC50 value of 111.2 μM. Compounds 1-3 also suppressed production of disease exacerbatory cytokines IL-6 and IL-10 but had minimal effect on nitric oxide production in L. donovani-infected macrophages, indicating that antileishmanial activity of these compounds is mediated via an NO-independent mechanism. Therefore, these new natural products could represent promising scaffolds for drug design studies for leishmaniasis.

Figure 1

Chemical structures of isolated metabolites 1−3.

Figure 2

Effect of treatment with metabolites 1−3 isolated from N. leucantha in bone marrow-derived macrophages (BMDMs) infected with L. donovani parasites. MØ (macrophages); MØI (infected macrophages); MØ+LPS (macrophages plus LPS); MØI+LPS (infected macrophages plus LPS). IL-6 (A) and IL-10 (B) cytokines levels were measured by ELISA in supernatant from BMDMs treated for 72 h. Mean cytokine level was expressed as pg/mL ± SE.