Lin Yun-Lian, Lee Yi-Chao, Huang Chuen-Lin, Lai Wen-Lin, Lin Yen-Ru, Huang Nai-Kuei
National Research Institute of Chinese Medicine, No. 155-1, Li-Nung Street, Section 2, Shipai, Peitou, Taipei 112, Taiwan.
J Ethnopharmacol. 2007 Feb 12;109(3):428-34. doi: 10.1016/j.jep.2006.08.012. Epub 2006 Aug 15.
Ligusticum chuanxiong (LC) is a traditional Chinese herbal medicine used to treat various cardiovascular diseases. In this study, the butanol extract of LC was found to protect neuronal-like pheochromocytoma cells from serum deprivation-induced apoptosis. Both a serine/threonine kinase inhibitor and a specific protein kinase A (PKA) inhibitor blocked the protective effect of LC. A transcription inhibitor (actinomycin D) and a protein synthesis inhibitor (cyclohexamide) also attenuated the protective effect of LC, suggesting the requirement of gene expression for the protection of LC. On the other hand, LC increased both the formation of cyclic-AMP and the phosphorylation of the cyclic-AMP response element-binding protein (CREB), a downstream target of PKA and a nuclear transcription factor known for neuroprotective mechanism. Furthermore, LC-induced CREB phosphorylation and protective effect could be blocked by a PKA inhibitor and overexpression of the dominant negative CREB, respectively. Taken together, the protective mechanism of LC in antagonizing serum deprivation-induced PC12 cell apoptosis might be mediated through a PKA/CREB-dependent pathway.
川芎是一种用于治疗各种心血管疾病的传统中草药。在本研究中，发现川芎的丁醇提取物可保护神经元样嗜铬细胞瘤细胞免受血清剥夺诱导的凋亡。丝氨酸/苏氨酸激酶抑制剂和特异性蛋白激酶A（PKA）抑制剂均阻断了川芎的保护作用。转录抑制剂（放线菌素D）和蛋白质合成抑制剂（环己酰亚胺）也减弱了川芎的保护作用，表明川芎发挥保护作用需要基因表达。另一方面，川芎增加了环磷酸腺苷（cAMP）的生成以及cAMP反应元件结合蛋白（CREB）的磷酸化，CREB是PKA的下游靶点，也是一种以神经保护机制而闻名的核转录因子。此外，PKA抑制剂和显性负性CREB的过表达分别可阻断川芎诱导的CREB磷酸化和保护作用。综上所述，川芎拮抗血清剥夺诱导的PC12细胞凋亡的保护机制可能是通过PKA/CREB依赖性途径介导的。
