Chattipakorn Siriporn, Pongpanparadorn Anucha, Pratchayasakul Wasana, Pongchaidacha Anchalee, Ingkaninan Kornkanok, Chattipakorn Nipon
Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand.
J Ethnopharmacol. 2007 Mar 1;110(1):61-8. doi: 10.1016/j.jep.2006.09.007. Epub 2006 Sep 10.
The current pharmacotherapy for Alzheimer's disease (AD) is the use of acetylcholinesterase inhibitors (AChE-Is). A previous in vitro study showed that Tabernaemontana divaricata extract (TDE) can inhibit AChE activity. However, neither the AChE inhibitory effects nor the effect on neuronal activity of TDE has been investigated in vivo. To determine those effects of TDE in animal models, the Ellman's colorimetric method was implemented to investigate the cortical and circulating cholinesterase (ChE) activity, and Fos expression was used to determine the neuronal activity in the cerebral cortex, following acute administration of TDE with various doses (250, 500 and 1000 mg/kg) and at different time points. All doses of TDE 2 h after a single administration significantly inhibited cortical AChE activity and enhanced neuronal activity in the cerebral cortex. The enhancement of Fos expression and AChE inhibitory effects in the cerebral cortex among the three TDE-treated groups was not significantly different. A 2 h interval following all doses of TDE administration had no effect on circulating ChE activity. However, TDE significantly inhibited circulating AChE 10, 30 and 60 min after administration. Our findings suggest that TDE is a reversible AChE-I and could be beneficial as a novel therapeutic agent for AD.
目前用于治疗阿尔茨海默病（AD）的药物疗法是使用乙酰胆碱酯酶抑制剂（AChE-Is）。先前的一项体外研究表明，狗牙花提取物（TDE）可以抑制乙酰胆碱酯酶（AChE）的活性。然而，TDE对AChE的抑制作用及其对神经元活性的影响尚未在体内进行研究。为了确定TDE在动物模型中的这些作用，采用埃尔曼比色法研究了不同剂量（250、500和1000mg/kg）的TDE在不同时间点急性给药后皮质和循环胆碱酯酶（ChE）的活性，并使用Fos表达来确定大脑皮质中的神经元活性。单次给药2小时后，所有剂量的TDE均显著抑制皮质AChE活性，并增强大脑皮质中的神经元活性。三个TDE治疗组中大脑皮质Fos表达的增强和AChE抑制作用没有显著差异。所有剂量的TDE给药后2小时间隔对循环ChE活性没有影响。然而，TDE在给药后10、30和60分钟显著抑制循环AChE。我们的研究结果表明，TDE是一种可逆的AChE抑制剂，作为一种新型的AD治疗药物可能有益。
