Essid Rym, Damergi Bilel, Fares Nadia, Jallouli Selim, Limam Ferid, Tabbene Olfa
Laboratory of Bioactive Substances, Biotechnology Center of Borj-Cedria Technopole, Hammam-Lif, Tunisia.
Int J Environ Health Res. 2024 Jul;34(7):2687-2701. doi: 10.1080/09603123.2023.2267470. Epub 2023 Oct 19.
Combination therapy at appropriately suitable doses presents a promising alternative to monotherapeutic drugs. In this study, and essential oils and their major compounds have exhibited substantial leishmaniacidal potential against both promastigote and amastigote forms of . However, they displayed high cytotoxicity against Raw264.7 macrophage cells. Interestingly, when combined with each other or with amphotericin B, they demonstrated a synergistic effect (FIC<0.5) with low cytotoxicity. These combinations are able to modulate the production of nitric oxide (NO) by macrophages. Notably, the combination of Essential oil with amphotericin B stimulates macrophage cells by increasing NO production to eliminate leishmanial parasites. Furthermore, investigation of the molecular mechanism of action of these synergistic combinations reveals potent inhibition of the sterol pathway through the inhibition of the CYP51 gene expression. The findings suggest that combination therapy may offer significant therapeutic benefits in both food and pharmaceutical fields.
以适当合适剂量进行联合治疗是单一治疗药物的一种有前景的替代方法。在本研究中，[两种精油及其主要化合物]对[利什曼原虫]的前鞭毛体和无鞭毛体形式均表现出显著的杀利什曼原虫潜力。然而，它们对Raw264.7巨噬细胞显示出高细胞毒性。有趣的是，当它们相互组合或与两性霉素B组合时，表现出协同作用（FIC<0.5）且细胞毒性低。这些组合能够调节巨噬细胞产生一氧化氮（NO）。值得注意的是，[某种精油]与两性霉素B的组合通过增加NO产生来刺激巨噬细胞以消除利什曼原虫寄生虫。此外，对这些协同组合作用分子机制的研究揭示了通过抑制CYP51基因表达对甾醇途径的有效抑制。研究结果表明联合治疗可能在食品和制药领域都提供显著的治疗益处。
