Peng Cheng, Wang Lan, Wang Yan-Hong, Li Yun-Xia, Pan Yuan
Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
Eur J Drug Metab Pharmacokinet. 2009 Jul-Sep;34(3-4):213-20. doi: 10.1007/BF03191176.
The study was to investigate the effect and action mechanism of aconitine and emodin on the function of the interstitial cells of Cajal (ICC) cultured in vitro. ICC cells were treated with aconitine (0.05-8%) and emodin (0.001-2%) in single or combined synchronous experiments and the effect of emodin on aconitine was evaluated using cell viability as end-point. Both the two compounds had toxicity on ICC cell. The cell membrane integrity impairment caused by the exposure lead to the efflux of intracellular ionic ([Na+], [Ca2+] and [K+]) and the deactivation of the Na+-K+-ATPase. The ionic disturbance caused the interruption of the cellular breathing chain and resulted in anaerobic metabolism increase and the glycogen massive decomposition, at last the energy metabolism in the cells was obstructed. But the antagonist effect existed when the two compounds were exposed to ICC cells together. The compatibility (aonitine:emodin as 2:1), can significantly reversed the toxicity of aconition. In addition, synergistic effects were never observed in the range of concentrations considered. Although emodin can defer the aconition's toxicity on ICC cell, the impairment can't be totally inhibited by the compatibility with time went on. The results of our work represent a starting point to generate novel information on the interactions between aconitine and emodin in vitro, as well as a new relevant experimental approach useful to investigate the Herb compatibility with aconite and rhubarb and reference for the clinic.
本研究旨在探讨乌头碱和大黄素对体外培养的 Cajal 间质细胞（ICC）功能的影响及作用机制。在单因素及联合同步实验中，用乌头碱（0.05 - 8%）和大黄素（0.001 - 2%）处理 ICC 细胞，并以细胞活力为终点评价大黄素对乌头碱的影响。两种化合物对 ICC 细胞均有毒性。暴露导致的细胞膜完整性损伤致使细胞内离子（[Na⁺]、[Ca²⁺]和[K⁺]）外流以及 Na⁺-K⁺-ATP 酶失活。离子紊乱导致细胞呼吸链中断，致使无氧代谢增加和糖原大量分解，最终细胞内能量代谢受阻。但当两种化合物共同作用于 ICC 细胞时存在拮抗作用。配伍（乌头碱：大黄素为 2:1）可显著逆转乌头碱的毒性。此外，在所考察的浓度范围内未观察到协同作用。尽管大黄素可延缓乌头碱对 ICC 细胞的毒性，但随着时间推移，配伍并不能完全抑制损伤。我们的研究结果为体外乌头碱与大黄素相互作用产生新信息提供了一个起点，同时也是一种用于研究草乌与大黄配伍的新的相关实验方法，可为临床提供参考。
