Neurotoxicity of veratrum nigrum L. and the molecular mechanism of veratridine toxicity

作者:Zhang, Xianxie; Wang, Yanli; Shao, Shuai; Wu, Yan; Wang, Yuguang; Ma, Zengchun; Yuan, Hailong; Gao, Yue*
来源:International Journal of Clinical and Experimental Medicine, 2018, 11(7): 6547-6559.

摘要

Veratrum nigrum L. has been used as an herbal preparation in worldwide for treatment of blood-stroke, excessive phlegm, epilepsy, etc. Veratridine is both active and toxic constituents of Veratrum nigrum L., which has been reported to affect excitable membranes, peripheral nerves, and skeletal and cardiac muscle. Previous work and literature research are reported that veratridine can act on the central nervous system. Therefore, it is very meaningful to study the neurotoxicity of veratridine. Cell viability, LDH release, ROS generation, MMP expression, Ca2+ concentration and apoptosis were measured to evaluate the neurotoxic mechanism of veratridine in SH-SY5Y cells. A positive injury model was established with glutamic acid in SH-SY5Y cells and Western blot was used to correlate toxicity with the MAPK signaling pathway. The results show that veratridine causes, MMP expression changes, Ca2+ accumulation in the cytoplasm, increased ROS and LDH releasing and SH-SY5Y cell membrane damage. SH-SY5Y cell viability diminished due to apoptosis. The MAPK signaling pathway is activated by veratridine, and driving forward apoptosis. The study provided evidence of the neurotoxic caused by veratridine and revealed the molecular mechanism behind its neurotoxic effects.