期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 91, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2020.107291
关键词
Leishmania donovani; Eugenol oleate; Amphotericin B; Synergism; Pro-inflammatory cytokines
资金
- SASTRA Deemed to be University
- FNDR, Bangalore India [G170021]
The combination of eugenol oleate and amphotericin B demonstrates synergistic effects in experimental visceral leishmaniasis, reducing the toxicity of amphotericin B and significantly decreasing parasite burden.
Present treatment regimen on visceral leishmaniasis has multiple limitations including severe side effects, toxicity, and resistance of Leishmania strains. Amphotericin B is a well-established pharmacologically approved drug; however, mainly toxicity is a foremost issue with that drug. Recently, our group identified eugenol oleate as an anti-leishmanial immunomodulatory compound. The important objectives of this present study was to evaluate the possible synergistic effect of eugenol oleate with amphotericin B to reduce the toxicity of this approved drug. Results obtained from this study signified that combination of eugenol oleate and amphotericin B showed indifferent combinatorial effect against promastigotes with x sigma FIC 1.015, while, moderate synergistic activity with x sigma FIC 0.456 against amastigotes. It was also notable that eugenol oleate (2.5 mu M) with low concentrations of amphotericin B (0.3125 mu M) showed 96.45% parasite reduction within L. donovani-infected murine macrophages. Furthermore, eugenol oleate and amphotericin B significantly (p < 0.01) enhanced the nitrite generation, and pro-inflammatory cytokines (IL-12, IFN-gamma and TNF-alpha) in infected macrophages in vitro and in BALB/c mice in vivo. Eugenol oleate (10 mg/Kg b. wt.) with amphotericin B (1 mg/Kg b.wt.) significantly (p < 0.01) controlled the parasite burden in liver by 96.2% and in spleen by 93.12%. Hence, this study strongly suggested the synergic potential of eugenol oleate with low concentration of amphotericin B in experimental visceral leishmaniasis through anti-leishmanial immune response.
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