Mohammed Magdy Mostafa Desoky, Mohammed Hala Sh, El Wafa Salwa A Abu, Ahmed Doaa A, Heikal Elham A, Elgohary Islam, Barakat Ashraf M
Pharmacognosy Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Giza, 12622, Egypt.
Pharmacognosy and Medicinal Plants Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.
Sci Rep. 2025 Jan 3;15(1):624. doi: 10.1038/s41598-024-82787-9.
Toxoplasmosis induced by Toxoplasma gondii is a well-known health threat, that prompts fatal encephalitis increased with immunocompromised patients, in addition, it can cause chorioretinitis, microcephaly, stillbirth in the fetus and even led to death. Standard therapy uses sulfadiazine and pyrimethamine drugs revealed beneficial results during the acute stage, however, it has severe side effects. UPLC-ESI-MS/MS used to explore C. limon MeOH ext. constituents, which revealed a list of 41 metabolites of different classes encompasses; unsaturated fatty acid, tricarboxylic acids, phenolic aldehyde, phenolic acids, phenolic glycosides, coumarins, sesquiterpene lactone, limonoid, steroid and flavonoids. C. limon MeOH ext. and the isolates reduced significantly the number of T. gondii tachyzoites. Consequently, histopathological examination, proved significant reduction in the number of mononuclear inflammatory cells in the kidney and liver sections, besides, lowering the number of shrunken and degenerative neurons in the brain sections of infected mice. Molecular docking study was performed targeted certain receptors, which are important for the life cycle fundamentals for the parasite mobility including invasion and egress, and further molecular dynamics simulation was conducted to get insights into the structural changes of the formed complexes, along with a pharmacophoric mapping approach, that confirmed the need for a free hydroxyl group and/or a phenolic substituted one, in order to form HB, Hyd/Aro and ML interactions, through which, cell cycle disruption via iron chelation, could be achieved. In addition, the ADMIT properties of all identified metabolites were predicted.
由刚地弓形虫引起的弓形虫病是一种众所周知的健康威胁，它会导致免疫功能低下的患者患致命性脑炎的几率增加。此外，它还会引起脉络膜视网膜炎、小头畸形、胎儿死产，甚至导致死亡。标准疗法使用磺胺嘧啶和乙胺嘧啶药物，在急性期显示出有益效果，然而，它有严重的副作用。超高效液相色谱-电喷雾串联质谱法用于探索柠檬桉甲醇提取物的成分，结果显示有41种不同类别的代谢物，包括不饱和脂肪酸、三羧酸、酚醛、酚酸、酚糖苷、香豆素、倍半萜内酯、柠檬苦素、甾体和黄酮类化合物。柠檬桉甲醇提取物及其分离物显著减少了刚地弓形虫速殖子的数量。因此，组织病理学检查证明，感染小鼠肾脏和肝脏切片中的单核炎性细胞数量显著减少，此外，脑切片中萎缩和变性神经元的数量也有所减少。针对某些对寄生虫移动性（包括入侵和逸出）的生命周期基础很重要的受体进行了分子对接研究，并进行了进一步的分子动力学模拟，以深入了解形成的复合物的结构变化，同时采用药效团映射方法，证实需要一个游离羟基和/或一个酚取代基，以形成氢键、疏水/芳香相互作用和π-阳离子相互作用，通过这些相互作用，可以通过铁螯合实现细胞周期的破坏。此外，还预测了所有鉴定出的代谢物的ADMIT性质。
