Utage Bhimashankar, Patole Milind, Nagvenkar Punam, Gacche Rajesh
National Centre for Cell Science, NCCS Complex, Pune, 411007, MS, India.
Department of Biotechnology, Savitribai Phule Pune University, Pune, 411007, MS, India.
J Tradit Complement Med. 2023 Jun 29;13(6):611-622. doi: 10.1016/j.jtcme.2023.06.003. eCollection 2023 Nov.
Leishmaniasis is endemic in more than 60 countries with a large number of mortality cases. The current chemotherapy approaches employed for managing the leishmaniasis is associated with severe side effects. Therefore there is a need to develop effective, safe, and cost affordable antileishmanial drug candidates.
This study was designed to evaluate the antileishmanial activity of a leaves extract (PJLME) towards the parasites.
PJLME was evaluated for its cytotoxicity against the parasites and the mouse macrophage cells. Further, various experiments like ROS assay, mitochondrial membrane potential assay, annexin v assay, cell cycle assay, and caspase 3/7 assay were performed to understand the mechanism of cell death. Phytochemical profiling of was performed by utilizing HPTLC and GC-MS analysis.
PJLME demonstrated antileishmanial activity at a remarkably lower concentration of IC 6.5 μg/mL. Of note, interestingly PJLME IC concentration has not demonstrated cytotoxicity against the mouse macrophage cell line. Performed experiments confirmed ROS inducing potential of PJLME which adversely affected the mitochondrial membrane potential and caused loss of mitochondrial membrane potential and thereby ATP levels. PJLME also arrested the cell cycle and induced apoptotic-like cell death in PJLME treated promastigotes.
The results clearly established the significance of as an effective and safe natural resource for managing visceral leishmaniasis. The findings can be used as a baseline reference for developing novel leads/formulations for effective management of visceral leishmaniasis.
利什曼病在60多个国家呈地方流行，有大量死亡病例。目前用于治疗利什曼病的化疗方法伴有严重副作用。因此，需要开发有效、安全且经济实惠的抗利什曼病候选药物。
本研究旨在评估一种叶提取物（PJLME）对寄生虫的抗利什曼病活性。
评估PJLME对寄生虫和小鼠巨噬细胞的细胞毒性。此外，进行了各种实验，如活性氧（ROS）测定、线粒体膜电位测定、膜联蛋白V测定、细胞周期测定和半胱天冬酶3/7测定，以了解细胞死亡机制。利用高效薄层色谱（HPTLC）和气相色谱 - 质谱（GC - MS）分析对其进行植物化学剖析。
PJLME在显著较低的IC浓度6.5μg/mL时表现出抗利什曼病活性。值得注意的是，有趣的是PJLME的IC浓度未对小鼠巨噬细胞系表现出细胞毒性。所进行的实验证实了PJLME诱导ROS的潜力，这对线粒体膜电位产生不利影响，导致线粒体膜电位丧失，进而导致ATP水平下降。PJLME还使细胞周期停滞，并在经PJLME处理的前鞭毛体中诱导类似凋亡的细胞死亡。
结果清楚地确立了作为治疗内脏利什曼病的有效且安全的天然资源的重要性。这些发现可作为开发有效治疗内脏利什曼病的新型先导化合物/制剂的基线参考。
