Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, 741235, West Bengal, India.
Sci Rep. 2020 Nov 24;10(1):20440. doi: 10.1038/s41598-020-77066-2.
Leishmaniasis, a major neglected tropical disease, affects millions of individuals worldwide. Among the various clinical forms, visceral leishmaniasis (VL) is the deadliest. Current antileishmanial drugs exhibit toxicity- and resistance-related issues. Therefore, advanced chemotherapeutic alternatives are in demand, and currently, plant sources are considered preferable choices. Our previous report has shown that the chloroform extract of Corchorus capsularis L. leaves exhibits a significant effect against Leishmania donovani promastigotes. In the current study, bioassay-guided fractionation results for Corchorus capsularis L. leaf-derived β-sitosterol (β-sitosterol) were observed by spectroscopic analysis (FTIR, H NMR, C NMR and GC-MS). The inhibitory efficacy of this β-sitosterol against L. donovani promastigotes was measured (IC = 17.7 ± 0.43 µg/ml). β-Sitosterol significantly disrupts the redox balance via intracellular ROS production, which triggers various apoptotic events, such as structural alteration, increased storage of lipid bodies, mitochondrial membrane depolarization, externalization of phosphatidylserine and non-protein thiol depletion, in promastigotes. Additionally, the antileishmanial activity of β-sitosterol was validated by enzyme inhibition and an in silico study in which β-sitosterol was found to inhibit Leishmania donovani trypanothione reductase (LdTryR). Overall, β-sitosterol appears to be a novel inhibitor of LdTryR and might represent a successful approach for treatment of VL in the future.
利什曼病是一种主要的被忽视热带病，影响着全球数百万人。在各种临床形式中，内脏利什曼病（VL）是最致命的。目前的抗利什曼病药物存在毒性和耐药性相关问题。因此，需要先进的化疗替代品，而目前植物来源被认为是首选。我们之前的报告表明，黄花菜叶的氯仿提取物对杜氏利什曼原虫前鞭毛体具有显著的作用。在当前的研究中，通过光谱分析（FTIR、H NMR、C NMR 和 GC-MS）观察到了从黄花菜叶中分离得到的 β-谷甾醇（β-sitosterol）的生物测定指导的分馏结果。该 β-谷甾醇对杜氏利什曼原虫前鞭毛体的抑制效果进行了测量（IC = 17.7 ± 0.43 µg/ml）。β-谷甾醇通过细胞内 ROS 的产生显著破坏氧化还原平衡，从而引发各种凋亡事件，如结构改变、脂滴储存增加、线粒体膜去极化、磷脂酰丝氨酸外化和非蛋白巯基耗竭。此外，通过酶抑制和计算机模拟研究验证了 β-谷甾醇的抗利什曼原虫活性，结果发现β-谷甾醇可以抑制杜氏利什曼原虫的三磷酸鸟苷还原酶（LdTryR）。总的来说，β-谷甾醇似乎是一种新型的 LdTryR 抑制剂，可能代表着未来治疗 VL 的一种成功方法。
