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穿心莲内酯的抗丝虫功效:对牛丝虫寄生虫鹿丝状线虫的体外研究。

Antifilarial efficacy of andrographolide: Ex vivo studies on bovine filarial parasite Setaria cervi.

作者信息

Yadav Smita, Ahmad Faiyaz, Rathaur Sushma

机构信息

Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India.

Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2022 Nov;261:109442. doi: 10.1016/j.cbpc.2022.109442. Epub 2022 Aug 18.

DOI:10.1016/j.cbpc.2022.109442
PMID:35985449
Abstract

Lymphatic filariasis caused by filarial nematode is an important disease leading to considerable morbidity throughout tropical countries. Even after specific elimination programs, the disease continue to spread in endemic countries. Thus newer therapeutic interventions are urgently needed to control the spread. In the present study, we have seen the effect of andrographolide (andro), a diterpenoid lactone from the leaves of Andrographis paniculata on filarial parasite Setaria cervi. There was time and concentration dependent decrease in motility and viability leading to death of parasite after 6 h of the exposure of andro. Andro showed potential antifilarial activity with an IC value of 24.80 μM assessed through MTT assay. There was concentration dependent decrease in the antioxidant enzymes activity and increase in proapoptotic markers after 5 h exposure of andro. Further, molecular docking analysis revealed that andro binds with filarial glutathione-S-transferase at glutathione (GSH) binding site and inhibiting enzyme activity competitively. Andro induced oxidative stress mediated apoptosis in parasites as evidenced by increase in the intracellular reactive oxygen species (ROS) and apoptotic markers.Therefore this study suggested that andro could be further explored as a new antifilarial drug.

摘要

由丝虫线虫引起的淋巴丝虫病是一种重要疾病,在整个热带国家导致相当高的发病率。即使在实施特定的消除计划之后,该病仍在流行国家继续传播。因此,迫切需要更新的治疗干预措施来控制其传播。在本研究中,我们观察了穿心莲内酯(andro)(一种从穿心莲叶片中提取的二萜内酯)对丝状寄生虫鹿丝状线虫的作用。暴露于andro 6小时后,寄生虫的活力和生存能力出现时间和浓度依赖性下降,最终导致死亡。通过MTT试验评估,andro显示出潜在的抗丝虫活性,IC值为24.80μM。暴露于andro 5小时后,抗氧化酶活性呈浓度依赖性下降,促凋亡标志物增加。此外,分子对接分析表明,andro在谷胱甘肽(GSH)结合位点与丝状谷胱甘肽-S-转移酶结合,并竞争性抑制酶活性。如细胞内活性氧(ROS)和凋亡标志物增加所证明的,andro诱导寄生虫发生氧化应激介导的凋亡。因此,本研究表明andro可作为一种新型抗丝虫药物进行进一步探索。

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