Ullah Rizwan, Rehman Abdur, Zafeer Mohd Faraz, Rehman Lubna, Khan Yasir A, Khan M A Hannan, Khan Shahper N, Khan Asad U, Abidi S M A
Section of Parasitology, Department of Zoology, Aligarh Muslim University, Aligarh, India.
Interdisciplinary Brain Research Centre (IBRC), J. N. Medical College, Aligarh Muslim University, Aligarh, India.
PLoS One. 2017 Feb 2;12(2):e0171267. doi: 10.1371/journal.pone.0171267. eCollection 2017.
Fasciolosis an economically important global disease of ruminants in the temperate and tropical regions, caused by Fasciola hepatica and F. gigantica, respectively, also poses a potential zoonotic threat. In India alone it causes huge losses to stakeholders. Anthelmintics including triclabendazole have been used to control this menace but the emerging resistance against the available compounds necessitates identification of novel and alternative therapeutic measures involving plant derived natural compounds for their anthelmintic potential. Thymoquinone (T) and curcumin (C), the active ingredients of Nigella sativa and Curcuma longa respectively have been used as antiparasitic agents but the information on their flukicidal effect is very limited. Adult flukes of F. gigantica were in vitro exposed to different concentrations of thymoquinone and curcumin separately for 3h at 37+ 1°C. A significant (p<0.05) reduction in the worm motility at 60 μM concentration of both T and C was observed though all the worms remained alive after 3h exposure, whereas the effect on egg shedding was statistically insignificant. Pronounced tegumental disruptions and erosion of spines in the posterior region and around the acetabulum was evident. A significant (p<0.05) decrease in glutathione-S-transferase and superoxide dismutase activity and reduced glutathione (GSH) level was observed, while protein carbonylation increased differentially. A significant inhibition of CathepsinL (CatL) gene expression in thymoquinone treated worms was also evident. Further, in silico molecular docking of T and C with CatL revealed a stronger interaction of curcumin with the involvement of higher number of amino acids as compared to thymoquinone that could be more effective in inhibiting the antioxidant enzymes of F. gigantica. It is concluded that both the compounds understudy will decrease the detoxification ability of F. gigantica, while inhibition of CatL will significantly affect their virulence potential. Thus, both thymoquinone and curcumin appeared to be promising anthelmintic compounds for further investigations.
肝片吸虫病是一种在温带和热带地区对反刍动物具有重要经济影响的全球性疾病，分别由肝片吸虫和巨片吸虫引起，它还构成潜在的人畜共患病威胁。仅在印度，它就给利益相关者造成了巨大损失。包括三氯苯达唑在内的驱虫药已被用于控制这种威胁，但对现有化合物出现的耐药性使得有必要确定涉及植物源天然化合物驱虫潜力的新型替代治疗措施。百里醌（T）和姜黄素（C）分别是黑种草和姜黄的活性成分，已被用作抗寄生虫剂，但关于它们杀吸虫作用的信息非常有限。将巨片吸虫的成虫在37±1°C下分别暴露于不同浓度的百里醌和姜黄素中3小时。在T和C浓度均为60μM时，观察到蠕虫活力显著（p<0.05）降低，尽管暴露3小时后所有蠕虫仍存活，而对排蛋的影响在统计学上不显著。明显可见后部区域和吸盘周围的体表明显破坏和棘突侵蚀。观察到谷胱甘肽-S-转移酶和超氧化物歧化酶活性显著（p<0.05）降低，还原型谷胱甘肽（GSH）水平降低，而蛋白质羰基化则有不同程度增加。在经百里醌处理的蠕虫中，组织蛋白酶L（CatL）基因表达也明显受到显著抑制。此外，T和C与CatL的计算机模拟分子对接显示，与百里醌相比，姜黄素与更多氨基酸的相互作用更强，这可能在抑制巨片吸虫的抗氧化酶方面更有效。得出的结论是，所研究的这两种化合物都会降低巨片吸虫的解毒能力，而对CatL的抑制将显著影响它们的毒力潜力。因此，百里醌和姜黄素似乎都是有前景的驱虫化合物，有待进一步研究。
