Li Yun Feng, Gong Zheng Hua, Yang Ming, Zhao Yi Min, Luo Zhi Pu
Division of Psychopharmacology, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, 100850 Beijing, China.
Life Sci. 2003 Jan 10;72(8):933-42. doi: 10.1016/s0024-3205(02)02331-7.
The mechanisms of the antidepressant action of the oligosaccharides (P(6)) extracted from Morinda Officinalis were studied. By flow cytometry analysis, treatment of PC12 cells with corticosterone (Cort) induced apoptosis in a concentration and time dependent manner. The highest percentage of apoptotic cells accumulated to 27.85 +/- 9.2% following pretreatment with Cort 10 microM for 5 d. In agarose gel electrophoresis of DNA, the sample obtained from PC12 cells pretreated with Cort 10 microM for 5 d showed a typical ladder pattern suggesting that Cort increased the DNA fragmentation significantly. Furthermore, the ultrastructure of Cort-treated cells displayed typical apoptosis-like morphological changes including fragmented chromatin accumulation to the inside of nucleolus membrane with a shape like crescent moon or ring, nuclear fragmentation or apoptotic body. In the presence of P(6), or tricyclic antidepressant desipramine (DIM), the apoptosis induced by Cort in the three measurements above was significantly inhibited. These results indicate that DIM or P(6) antagonize the apoptosis induced by Cort in PC12 cells, which may be one of the cellular mechanisms of their antidepressant effects.
对巴戟天中提取的低聚糖(P(6))的抗抑郁作用机制进行了研究。通过流式细胞术分析,用皮质酮(Cort)处理PC12细胞会以浓度和时间依赖性方式诱导细胞凋亡。在用10 microM的Cort预处理5天后,凋亡细胞的最高百分比累积至27.85 +/- 9.2%。在DNA的琼脂糖凝胶电泳中,从用10 microM的Cort预处理5天的PC12细胞获得的样品显示出典型的梯状条带模式,表明Cort显著增加了DNA片段化。此外,经Cort处理的细胞的超微结构显示出典型的凋亡样形态变化,包括染色质片段聚集到核仁膜内部,呈新月形或环形,核碎裂或凋亡小体。在存在P(6)或三环类抗抑郁药地昔帕明(DIM)的情况下,上述三种测量中Cort诱导的细胞凋亡被显著抑制。这些结果表明,DIM或P(6)拮抗Cort在PC12细胞中诱导的细胞凋亡,这可能是它们抗抑郁作用的细胞机制之一。