Caffeic acid and quercetin exert caspases-independent apoptotic effects on Leishmania major promastigotes, and reactivate the death of infected phagocytes derived from BALB/c mice
Journal Title: Asian Pacific Journal of Tropical Biomedicine - Year 2017, Vol 7, Issue 4
Abstract
Objective: To investigate the leishmanicidal effects of two antioxidants, caffeic acid and quercetin on Leishmania major (L. major) promastigotes in vitro, and their immunomodulatory effects on infected phagocytes derived from susceptible BALB/c mice. Methods: Caffeic acid and quercetin-induced cell death was examined by Pi-Hoechst double staining of L. major promastigotes and MTT assay, in the presence or absence of protease inhibitors in vitro. Caffeic acid or quercetin were administered subcutaneously to BALB/c mice infected with L. major promastigotes through a dorsal air pouch. Nitric oxide and superoxide anion production by phagocytes infiltrating the air pouch and the expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-a) and nuclear factor kappa B in the air pouch membrane were therefore evaluated using appropriate methods. Results: Caffeic acid and quercetin displayed a dose-dependent cytotoxic effect against L. major promastigotes, and induced cell death via caspases-independent pathways. In vivo, L. major promastigotes inoculation into air pouch cavity of BALB/c mice leads to a sequential influx of neutrophils (hours), followed by macrophages (days). Results showed that L. major delayed apoptosis of infected neutrophils and macrophages by the cleavage of the nuclear factor kappa B p65RelA subunit, and persisted by inhibiting TNF-a and iNOS expression and reactive oxygen species generation. Caffeic acid or quercetin restored reactive oxygen species production and TNF-a-induced iNOS activity, and abrogate apoptosis delay of infected phagocytes. Conclusions: The leishmanicidal effect of caffeic acid and quercetin on promastigotes and amastigotes, as well as reactivation of infected phagocytes apoptosis, suggested a potential therapeutic role against cutaneous leishmaniasis.
Authors and Affiliations
Radia Belkhelfa-Slimani, Bahia Djerdjouri
Keywords
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- EP ID EP250996
- DOI 10.1016/j.apjtb.2017.01.022
- Views 69
- Downloads 0
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