Saini Prasanta, Gayen Prajna, Nayak Ananya, Kumar Deepak, Mukherjee Niladri, Pal Bikas C, Sinha Babu Santi P
Parasitology Laboratory, Department of Zoology, School of Life Sciences, Visva-Bharati University, Santiniketan-731235, West Bengal, India.
Parasitol Int. 2012 Dec;61(4):520-31. doi: 10.1016/j.parint.2012.04.002. Epub 2012 Apr 26.
In the reported work the in vitro activity of a methanolic extract of leaves of Hibiscus mutabilis (Malvaceae) against bovine Setaria cervi worms has been investigated. Bioassay-guided fractionation led to isolation of ferulic acid from ethyl acetate fraction. The crude extract and ferulic acid, the active molecule, showed significant microfilaricidal as well as macrofilaricidal activities against the microfilaria (L(1)) and adult of S. cervi by both a worm motility and MTT reduction assay. The findings thus provide a new lead for development of a filaricidal drug from natural products. To examine the possible mechanism of action of ferulic acid, the involvement of apoptosis in adult worms of S. cervi was investigated. We found extreme cellular disturbances in ferulic acid-treated adult worms characterized by chromatin condensation, in situ DNA fragmentation and nucleosomal DNA laddering. In this work we are reporting for the first time that ferulic acid exerts its antifilarial effect through induction of apoptosis and by downregulating and altering the level of some key antioxidants (GSH, GST and SOD) of the filarial nematode S. cervi. Our results have provided experimental evidence supporting that ferulic acid causes an increased proapoptotic gene expression and decreased expression of anti-apoptotic genes simultaneously with an elevated level of ROS and gradual dose dependent decline of parasitic GSH level. We also observed a gradual dose dependent elevation of GST and SOD activity in the ferulic acid treated worms.
在已报道的工作中，对芙蓉（锦葵科）叶片甲醇提取物针对牛丝状网尾线虫的体外活性进行了研究。生物测定引导的分级分离导致从乙酸乙酯馏分中分离出阿魏酸。粗提物和活性分子阿魏酸通过蠕虫运动性和MTT还原试验对丝状网尾线虫的微丝蚴（L(1)）和成虫均显示出显著的杀微丝蚴和杀成虫活性。这些发现为从天然产物开发杀丝虫药物提供了新的线索。为了研究阿魏酸可能的作用机制，研究了丝状网尾线虫成虫凋亡的参与情况。我们发现阿魏酸处理的成虫中存在极端的细胞紊乱，其特征为染色质浓缩、原位DNA片段化和核小体DNA梯状条带。在这项工作中，我们首次报道阿魏酸通过诱导凋亡以及下调和改变丝状线虫丝状网尾线虫的一些关键抗氧化剂（谷胱甘肽、谷胱甘肽S-转移酶和超氧化物歧化酶）水平发挥其抗丝虫作用。我们的结果提供了实验证据，支持阿魏酸导致促凋亡基因表达增加和抗凋亡基因表达减少，同时活性氧水平升高以及寄生虫谷胱甘肽水平呈剂量依赖性逐渐下降。我们还观察到在阿魏酸处理的蠕虫中谷胱甘肽S-转移酶和超氧化物歧化酶活性呈剂量依赖性逐渐升高。
