Trailovic Sasa M, Rajkovic Milan, Marjanovic Djordje S, Neveu Cédric, Charvet Claude L
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Department of Biology, Faculty of Veterinary Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Pharmaceuticals (Basel). 2021 May 26;14(6):505. doi: 10.3390/ph14060505.
sp. is the only ascarid parasitic nematode in equids and one of the most threatening infectious organisms in horses. Only a limited number of compounds are available for treatment of horse helminthiasis, and sp. worms have developed resistance to the three major anthelmintic families. In order to overcome the appearance of resistance, there is an urgent need for new therapeutic strategies. The active ingredients of herbal essential oils are potentially effective antiparasitic drugs. Carvacrol is one of the principal chemicals of essential oil from , , , , and herbs. However, the antiparasitic mode of action of carvacrol is poorly understood. Here, the objective of the work was to characterize the activity of carvacrol on sp. nicotinic acetylcholine receptor (nAChR) function both in vivo with the use of worm neuromuscular flap preparations and in vitro with two-electrode voltage-clamp electrophysiology on nAChRs expressed in oocytes. We developed a neuromuscular contraction assay for body flaps and obtained acetylcholine concentration-dependent contraction responses. Strikingly, we observed that 300 µM carvacrol fully and irreversibly abolished sp. muscle contractions elicited by acetylcholine. Similarly, carvacrol antagonized acetylcholine-induced currents from both the nicotine-sensitive AChR and the morantel-sensitive AChR subtypes. Thus, we show for the first time that body muscle flap preparation is a tractable approach to investigating the pharmacology of sp. neuromuscular system. Our results suggest an intriguing mode of action for carvacrol, being a potent antagonist of muscle nAChRs of sp. worms, which may account for its antiparasitic potency.
[虫名]是马属动物中唯一的蛔科寄生线虫，也是马类最具威胁性的感染性生物之一。目前仅有有限的几种化合物可用于治疗马的蠕虫病，而[虫名]已对三大类驱虫药产生了抗性。为了克服抗药性的出现，迫切需要新的治疗策略。草药精油的活性成分可能是有效的抗寄生虫药物。香芹酚是[多种植物名称]等植物精油的主要化学成分之一。然而，香芹酚的抗寄生虫作用方式尚不清楚。在此，本研究的目的是通过使用蠕虫神经肌肉皮瓣制剂在体内以及利用双电极电压钳电生理学在卵母细胞中表达的烟碱型乙酰胆碱受体（nAChR）上进行体外实验，来表征香芹酚对[虫名]nAChR功能的活性。我们开发了一种针对[虫名]体皮瓣的神经肌肉收缩测定法，并获得了乙酰胆碱浓度依赖性收缩反应。令人惊讶的是，我们观察到300μM香芹酚完全且不可逆地消除了乙酰胆碱引起的[虫名]肌肉收缩。同样，香芹酚拮抗了来自尼古丁敏感型AChR和噻嘧啶敏感型AChR亚型的乙酰胆碱诱导电流。因此，我们首次表明体肌皮瓣制备是研究[虫名]神经肌肉系统药理学的一种可行方法。我们的结果表明香芹酚有一种有趣的作用方式，它是[虫名]蠕虫肌肉nAChRs的强效拮抗剂，这可能解释了它的抗寄生虫效力。
