Goel Vanshita, Sharma Sunidhi, Chakroborty Neloy Kumar, Singla Lachhman Das, Choudhury Diptiman
School of Chemistry and Biochemistry, Thapar Institute of Engineering & Technology, Patiala, 147004, Punjab, India.
Thapar School of Liberal Arts & Sciences, Thapar Institute of Engineering & Technology, Patiala, 147004, Punjab, India.
Heliyon. 2023 Feb 12;9(2):e13699. doi: 10.1016/j.heliyon.2023.e13699. eCollection 2023 Feb.
Prevalence of infection, limited choice of drugs, and emerging resistance against contemporary medications lead to a pressing need to develop new anthelmintic drugs and drug targets. However, little understanding of worms' physiology has substantially delayed the process. Here, we are reporting the tissue morphology of , intestinal parasitic helminths found in small ruminants, and targeting its nervous system with quercetin, a naturally occurring flavonoid. Quercetin showed anthelmintic activity against all of the developmental stages of . Further, histological analysis demonstrated damage to various body parts, including isthmus, brut, pseudocoele, and other organs. Mechanistic studies revealed the generation of oxidative stress and alterations in the activities of the stress response enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase. Moreover, the time-dependent imaging of reactive oxygen species (ROS) generated due to quercetin treatment disclosed neuropils as the primary targets of quercetin in adult worms, which eventually lead to the paralysis and death of the worms. Thus, this work demonstrates that the nervous system of the parasitic helminth, , is a novel target of the drug quercetin.
感染的普遍性、药物选择有限以及对当代药物新出现的耐药性导致迫切需要开发新的驱虫药物和药物靶点。然而,对蠕虫生理学的了解不足大大延缓了这一进程。在此,我们报告了在小型反刍动物中发现的肠道寄生蠕虫的组织形态,并以天然存在的类黄酮槲皮素作用于其神经系统。槲皮素对该蠕虫的所有发育阶段均显示出驱虫活性。此外,组织学分析表明该蠕虫的各个身体部位,包括峡部、盲管、假体腔和其他器官均受到损伤。机制研究揭示了氧化应激的产生以及应激反应酶(如过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶)活性的改变。此外,对槲皮素处理产生的活性氧(ROS)进行的时间依赖性成像显示,神经纤维是成年蠕虫中槲皮素的主要作用靶点,最终导致蠕虫麻痹和死亡。因此,这项工作表明寄生蠕虫的神经系统是药物槲皮素的一个新靶点。