Antileishmanial activity and immunomodulatory effect of secosubamolide, a butanolide isolated from Nectandra oppositifolia (Lauraceae)

Abstract Background: Visceral leishmaniasis is a complex neglected tropical disease caused by Leishmania donovani complex. Its current treatment reveals strong limitations, especially high toxicity. In this context, natural products are important sources of new drug alternatives for VL therapy. Ther...

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Bibliographic Details
Published in:Journal of Venomous Animals and Toxins including Tropical Diseases
Main Authors: Thais A. da Costa-Silva, Geanne A. Alves Conserva, Andrés J. Galisteo Jr, Andre G. Tempone, João Henrique G. Lago
Format: Article in Journal/Newspaper
Language:English
Published: SciELO
Subjects:
Leishmania (L.) infantum chagasi
Antileishmanial
Nectandra oppositifolia
Secosubamolide
Immunomodulatory
Arctic medicine. Tropical medicine
RC955-962
Toxicology. Poisons
RA1190-1270
Zoology
QL1-991
Arctic
Online Access:https://doi.org/10.1590/1678-9199-jvatitd-2019-0008
https://doaj.org/article/4da47e180d0245b59f81413ac7dbf6c9
Description
Summary:Abstract Background: Visceral leishmaniasis is a complex neglected tropical disease caused by Leishmania donovani complex. Its current treatment reveals strong limitations, especially high toxicity. In this context, natural products are important sources of new drug alternatives for VL therapy. Therefore, the antileishmanial and immunomodulatory activity of compounds isolated from Nectandra oppositifolia (Lauraceae) was investigated herein. Methods: The n-hexane extract from twigs of N. oppositifolia were subjected to HPLC/HRESIMS and bioactivity-guided fractionation to afford compounds 1 and 2 which were evaluated in vitro against Leishmania (L.) infantum chagasi and NCTC cells. Results: The n-hexane extract displayed activity against L. (L.) infantum chagasi and afforded isolinderanolide E (1) and secosubamolide A (2), which were effective against L. (L.) infantum chagasi promastigotes, with IC50 values of 57.9 and 24.9 µM, respectively. Compound 2 was effective against amastigotes (IC50 = 10.5 µM) and displayed moderate mammalian cytotoxicity (CC50 = 42 µM). The immunomodulatory studies of compound 2 suggested an anti-inflammatory activity, with suppression of IL-6, IL-10, TNF with lack of nitric oxide. Conclusion: This study showed the antileishmanial activity of compounds 1 and 2 isolated from N. oppositifolia. Furthermore, compound 2 demonstrated an antileishmanial activity towards amastigotes associated to an immunomodulatory effect.

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