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突尼斯洋甘菊精油中α-红没药醇的杀利什曼原虫活性。

Leishmanicidal activity of α-bisabolol from Tunisian chamomile essential oil.

作者信息

Hajaji Soumaya, Sifaoui Ines, López-Arencibia Atteneri, Reyes-Batlle María, Jiménez Ignacio A, Bazzocchi Isabel L, Valladares Basilio, Akkari Hafidh, Lorenzo-Morales Jacob, Piñero José E

机构信息

Laboratoire de Parasitologie, École Nationale de Médecine Vétérinaire de Sidi Thabet, Université de la Manouba, 2020, Manouba, Tunisie.

Faculté des sciences de Bizerte, Université de Carthage, 7021, Zarzouna, Tunisie.

出版信息

Parasitol Res. 2018 Sep;117(9):2855-2867. doi: 10.1007/s00436-018-5975-7. Epub 2018 Jun 28.

Abstract

According to the World Health Organization, leishmaniasis is considered as a major neglected tropical disease causing an enormous impact on global public health. Available treatments were complicated due to the high resistance, toxicity, and high cost. Therefore, the search for novel sources of anti-leishmania agents is an urgent need. In the present study, an in vitro evaluation of the leishmanicidal activity of the essential oil of Tunisian chamomile (Matricaria recutita L.) was carried out. Chamomile essential oil exhibits a good activity on promastigotes forms of L. amazonensis and L. infantum with a low inhibitory concentration at 50% (IC) (10.8 ± 1.4 and 10.4 ± 0.6 μg/mL, respectively). Bio-guided fractionation was developed and led to the identification of (-)-α-bisabolol as the most active molecule with low IC (16.0 ± 1.2 and 9.5 ± 0.1 μg/mL for L. amazonensis and L. infantum, respectively). This isolated sesquiterpene alcohol was studied for its activity on amastigotes forms (IC = 5.9 ± 1.2 and 4.8 ± 1.3 μg/mL, respectively) and its cytotoxicity (selectivity indexes (SI) were 5.4 and 6.6, respectively). The obtained results showed that (-)-α-bisabolol was able to activate a programmed cell death process in the promastigote stage of the parasite. It causes phosphatidylserine externalization and membrane damage. Moreover, it decreases the mitochondrial membrane potential and total ATP levels. These results highlight the potential use of (-)-α-bisabolol against both L. amazonensis and L. infantum, and further studies should be undertaken to establish it as novel leishmanicidal therapeutic agents.

摘要

根据世界卫生组织的说法,利什曼病被视为一种主要的被忽视热带病,对全球公共卫生造成巨大影响。由于高耐药性、毒性和高成本,现有的治疗方法很复杂。因此,迫切需要寻找新型抗利什曼原虫药物来源。在本研究中,对突尼斯洋甘菊(母菊)精油的杀利什曼原虫活性进行了体外评估。洋甘菊精油对亚马逊利什曼原虫和婴儿利什曼原虫的前鞭毛体形式表现出良好的活性,其50%抑制浓度(IC)较低(分别为10.8±1.4和10.4±0.6μg/mL)。开展了生物导向分级分离,鉴定出(-)-α-红没药醇是活性最强的分子,其IC较低(亚马逊利什曼原虫和婴儿利什曼原虫分别为16.0±1.2和9.5±0.1μg/mL)。对这种分离出的倍半萜醇对无鞭毛体形式的活性(IC分别为5.9±1.2和4.8±1.3μg/mL)及其细胞毒性进行了研究(选择性指数(SI)分别为5.4和6.6)。所得结果表明,(-)-α-红没药醇能够在寄生虫的前鞭毛体阶段激活程序性细胞死亡过程。它导致磷脂酰丝氨酸外化和膜损伤。此外,它降低线粒体膜电位和总ATP水平。这些结果突出了(-)-α-红没药醇对亚马逊利什曼原虫和婴儿利什曼原虫的潜在用途,应进一步开展研究以将其确立为新型杀利什曼原虫治疗药物。

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