Essid Rym, Kefi Sarra, Damergi Bilel, Abid Ghassen, Fares Nadia, Jallouli Selim, Abid Islem, Hussein Dina, Tabbene Olfa, Limam Ferid
Laboratory of Bioactive Substances, Biotechnology Center of Borj Cedria, BP 901, Hammam-Lif 2050, Tunisia.
University of Tunis-El Manar, Campus Universitaire Farhat Hached, BP-94 Rommana, Tunis 1068, Tunisia.
Molecules. 2024 Apr 19;29(8):1876. doi: 10.3390/molecules29081876.
The present study aimed to evaluate the leishmanicidal potential of the essential oil (EO) of () and to investigate its molecular mechanism of action by qPCR. Furthermore, in silicointeraction study of the major EO compounds with the enzyme cytochrome P450 sterol 14α-demethylase (CYP51) was also performed. EO was analyzed by gas chromatography-mass spectrometry (GC-MS). Results showed that α-pinene (26.44%), -cadinol (26.27%), caryophyllene Oxide (7.73 ± 1.04%), and α-Cadinene (3.79 ± 0.12%) are the major compounds of EO. However, limited antioxidant activity was observed, as this EO was ineffective in neutralizing DPPH free radicals and in inhibiting β-carotene bleaching. Interestingly, it displayed effective leishmanicidal potential against promastigote (IC of 6.79 and 5.25 μg/mL) and amastigote (IC of 8.04 and 7.32 μg/mL) forms of and , respectively. Molecular mechanism investigation showed that EO displayed potent inhibition on the thiol regulatory pathway. Furthermore, a docking study of the main components of the EO with cytochrome P450 sterol 14α-demethylase (CYP51) enzyme revealed that -cadinol exhibited the best binding energy values (-7.5 kcal/mol), followed by α-cadinene (-7.3 kcal/mol) and caryophyllene oxide (-7 kcal/mol). These values were notably higher than that of the conventional drug fluconazole showing weaker binding energy (-6.9 kcal/mol). These results suggest that EO could serve as a potent and promising candidate for the development of alternative antileishmanial agent in the treatment of leishmaniasis.
本研究旨在评估（）精油的杀利什曼原虫潜力，并通过定量聚合酶链反应（qPCR）研究其分子作用机制。此外，还对该精油的主要化合物与细胞色素P450固醇14α-脱甲基酶（CYP51）进行了计算机模拟相互作用研究。采用气相色谱-质谱联用（GC-MS）对该精油进行分析。结果表明，α-蒎烯（26.44%）、-杜松醇（26.27%）、氧化石竹烯（7.73±1.04%）和α-杜松烯（3.79±0.12%）是该精油的主要化合物。然而，观察到其抗氧化活性有限，因为该精油在中和二苯基苦味酰基自由基和抑制β-胡萝卜素漂白方面无效。有趣的是，它分别对和的前鞭毛体（IC为6.79和5.25μg/mL）和无鞭毛体（IC为8.04和7.32μg/mL）形式显示出有效的杀利什曼原虫潜力。分子机制研究表明，该精油对硫醇调节途径有显著抑制作用。此外，该精油主要成分与细胞色素P450固醇14α-脱甲基酶（CYP51）的对接研究表明，-杜松醇表现出最佳结合能值（-7.5千卡/摩尔），其次是α-杜松烯（-7.3千卡/摩尔）和氧化石竹烯（-7千卡/摩尔）。这些值明显高于传统药物氟康唑的结合能值（-6.9千卡/摩尔），后者结合能较弱。这些结果表明，该精油可作为开发治疗利什曼病替代抗利什曼原虫药物的有力且有前景的候选物。
