Inhibitory effects of isobavachalcone against Tetrahymena thermophila: Mechanistic insights

IF 4.3 3区环境科学与生态学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Comparative Biochemistry and Physiology C-toxicology & Pharmacology Pub Date : 2025-09-13 DOI:10.1016/j.cbpc.2025.110352

Hongming Tang , Juan Liu , Dong Sheng , Xu Ren , Qinghua Yu , Zhixin Guo , Yunpeng Wu , Yuxiao Liu , Yuehan Xiao , Wei Wang , Shigen Ye , Weijia Zhou

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Abstract

Isobavachalcone (IBC), a bioactive flavonoid derived from Psoralea corylifolia, exhibits potent anti-ciliate activity, but its underlying mechanism remains unclear. Utilizing Tetrahymena thermophila as a model organism, we demonstrated that IBC induces dose-dependent mortality (12 h-IC₅₀: 1.39 mg/L) and inhibits growth. Mechanistically, IBC triggers oxidative stress by elevating reactive oxygen species (ROS) and disrupting antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH). This disruption leads to membrane damage, as evidenced by lactate dehydrogenase (LDH) leakage and ATPase inhibition, as well as mitochondrial dysfunction. Microscopic examination and staining confirmed that cell death occurs via necrotic cell death rather than apoptosis. Transcriptome analysis revealed key pathways, including peroxisome-mediated oxidation, glutathione metabolism, and ATP-binding cassette (ABC) transporters, further supporting the role of IBC in oxidative and structural disruption. These findings elucidate the anti-ciliate mechanism of IBC, providing valuable insights for developing targeted anti-parasitic agents.

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异巴伐恰尔酮对嗜热四膜虫的抑制作用：机理研究。

异巴瓦恰尔酮（IBC）是一种从补骨脂中提取的具有生物活性的类黄酮，具有很强的抗纤毛虫活性，但其作用机制尚不清楚。利用嗜热四膜虫作为模式生物，我们证明了IBC诱导剂量依赖性死亡（12 h-IC50: 1.39 mg/L）并抑制生长。在机制上，IBC通过升高活性氧（ROS）和破坏抗氧化酶（包括超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽（GSH））触发氧化应激。这种破坏导致膜损伤，如乳酸脱氢酶（LDH）渗漏和atp酶抑制，以及线粒体功能障碍。显微镜检查和染色证实细胞死亡是通过坏死细胞死亡而不是凋亡发生的。转录组分析揭示了关键途径，包括过氧化物酶体介导的氧化、谷胱甘肽代谢和atp结合盒（ABC）转运蛋白，进一步支持IBC在氧化和结构破坏中的作用。这些发现阐明了IBC的抗纤毛虫机制，为开发靶向抗寄生虫药物提供了有价值的见解。

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来源期刊

Comparative Biochemistry and Physiology C-toxicology & Pharmacology 医学-动物学

CiteScore

7.50

自引率

5.10%

发文量

206

审稿时长

30 days

期刊介绍： Part C: Toxicology and Pharmacology. This journal is concerned with chemical and drug action at different levels of organization, biotransformation of xenobiotics, mechanisms of toxicity, including reactive oxygen species and carcinogenesis, endocrine disruptors, natural products chemistry, and signal transduction with a molecular approach to these fields.