Natural products from plants contain many interesting biomolecules. Among them, quercetin (Q), gallic acid (GA), and rutin (R) all have well-reported antileishmanial activity; however, their exact mechanisms of action are still not known. The current study is a step forward towards unveil the possible modes of action of these compounds against Leishmania donovani (the causative agent of visceral leishmaniasis). The selected compounds were checked for their mechanisms of action against L. donovani using different biological assays including apoptosis and necrosis evaluation, effects on genetic material (DNA), quantitative testing of nitric oxide production, ultrastructural modification via transmission electron microscopy, and real-time PCR analysis. The results confirmed that these compounds are active against L. donovani, with IC₅₀ values of 84.65 µg/mL, 86 µg/mL, and 98 µg/mL for Q, GA, and R, respectively. These compounds increased nitric oxide production and caused apoptosis and DNA damage, which led to changes in the treated cells’ ultrastructural behavior and finally to the death of L. donovani. These compounds also suppressed essential enzymes like trypanothione reductase and trypanothione synthetase, which are critical for leishmanial survival. The selected compounds have high antileishmanial potentials, and thus in-vivo testing and further screening are highly recommended.

中文翻译：

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生物类黄酮诱导的多诺瓦尼无鞭毛体和前鞭毛体的细胞凋亡和 DNA 损伤：破译作用方式

来自植物的天然产物含有许多有趣的生物分子。其中，槲皮素 (Q)、没食子酸 (GA) 和芦丁 (R) 均具有抗利什曼原虫活性。然而，它们的确切作用机制仍不清楚。目前的研究是朝着揭示这些化合物对多诺瓦利什曼原虫（内脏利什曼病的病原体）可能的作用方式迈出的一步。检查所选化合物对多诺瓦尼氏杆菌的作用机制使用不同的生物学分析，包括细胞凋亡和坏死评估、对遗传物质 (DNA) 的影响、一氧化氮产生的定量测试、通过透射电子显微镜进行的超微结构修饰和实时 PCR 分析。结果证实，这些化合物对多诺瓦氏杆菌具有活性，Q、GA 和 R 的IC ₅₀值分别为 84.65 µg/mL、86 µg/mL 和 98 µg/mL。这些化合物会增加一氧化氮的产生并导致细胞凋亡和 DNA 损伤，从而导致被处理细胞的超微结构行为发生变化，最终导致多诺瓦尼乳杆菌死亡. 这些化合物还抑制了对利什曼原虫生存至关重要的必需酶，例如锥虫硫酮还原酶和锥虫硫酮合成酶。所选化合物具有很高的抗利什曼病潜力，因此强烈建议进行体内测试和进一步筛选。