Department of Biological Sciences, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL, United States.
Microbiology Ph.D. Program, College of Science, Technology, Engineering and Mathematics, Alabama State University, Montgomery, AL, United States.
Front Cell Infect Microbiol. 2024 Nov 11;14:1368019. doi: 10.3389/fcimb.2024.1368019. eCollection 2024.
Apigeninidin chloride (APi) is a form of 3-deoxyanthrocyanidins (3-DAs) abundantly produced by the red plant. It has been previously reported to be effective against () tachyzoites grown with less cytotoxic effect. However, its possible mechanism(s) of action has not been elucidated. Biochemically, we discovered that APi induced high reactive oxygen species (ROS) and mitochondria superoxide (MitoSOX) productions in tachyzoites, leading to mitochondrial membrane potential (MMP) disruption .
To confirm our biochemical results at the molecular level, we performed a liquid chromatography-mass spectrometry (LC-MS) analysis on APi-treated parasites to assess any metabolite and lipid alterations often associated with high ROS/MitoSOX production in cells.
Noteworthy is that we detected several important oxidative stress-induced metabolites such as hexanal, aldehydes, methyl undeo10-enoate, butadiynyl phenyl ketone, 16-hydroxyhexadecanoic acid (16-OH, 16:0), 2-hydroxytricosanoic acid (C23:0; O), 3-oxodecanosanoic acid (C22:1; O), 2-hydroxypropylsterate, and furan fatty acids F6 (19FU-FA).
These metabolites are associated with lipid, protein, and nucleic acid disruptions. Using atovaquone (Atov) as a control, we observed that it disrupted intracellular tachyzoites' mitochondrial membrane potential, increased ROS and MitoSOX production, and altered metabolite and lipid production similar to what was observed with our experimental compound APi. Overall, our results indicated that APi targets tachyzoite growth through inducing oxidative stress, mitochondrial dysfunction, and eventually parasite death.
芹菜素氯化物（APi）是一种 3-去氧花青素（3-DAs），大量存在于红色植物中。先前的研究表明，APi 对生长的 速殖子有效，且细胞毒性较小。然而，其作用机制尚不清楚。从生化角度来看，我们发现 APi 诱导速殖子产生大量活性氧（ROS）和线粒体超氧化物（MitoSOX），导致线粒体膜电位（MMP）破坏。
为了在分子水平上证实我们的生化结果，我们对 APi 处理的寄生虫进行了液相色谱-质谱（LC-MS）分析，以评估与细胞中高 ROS/MitoSOX 产生相关的任何代谢物和脂质变化。
值得注意的是，我们检测到几种重要的氧化应激诱导代谢物，如己醛、醛类、甲基十一碳烯酸酯、丁二炔基苯甲酮、16-羟基十六烷酸（16-OH，16:0）、2-羟基二十三烷酸（C23:0；O）、3-氧癸烷酸（C22:1；O）、2-羟丙基硬脂酸酯和呋喃脂肪酸 F6（19FU-FA）。
这些代谢物与脂质、蛋白质和核酸的破坏有关。我们使用阿托伐醌（Atov）作为对照，观察到它破坏了细胞内速殖子的线粒体膜电位，增加了 ROS 和 MitoSOX 的产生，并改变了代谢物和脂质的产生，与我们实验化合物 APi 观察到的情况相似。总的来说，我们的结果表明，APi 通过诱导氧化应激、线粒体功能障碍，最终导致寄生虫死亡，来靶向 速殖子生长。
