Demethylbellidifolin Prevents Nitroglycerin Tolerance via Improved Aldehyde Dehydrogenase 2 Activity

作者：Shi, Rui-Zheng; Li, Xiao-Hui; Jia, Su-Jie; Fu, Qiong-Mei; Chen, Yue-Rong; Chen, Jia; Chen, An; Li, Shi-Xun; Tan, Gui-San; Li, Yuan-Jian; Zhang, Guo-Gang^*

来源：Planta Medica, 2009, 75(14): 1476-1481.

DOI：10.1055/s-0029-1185774

• demethylbellidifolin
• nitroglycerin tolerance
• reactive oxygen species
• aldehyde dehydrogenase 2

The aim of this study was to investigate the effect of demethylbellidifolin (DMB), a major xanthone compound of Swertia davidi Franch, on nitroglycerin (NTG) tolerance. In the in vivo portion of the study, pretreatment of Sprague-Dawley rats with NTG (10 mg/kg) for 8 days caused tolerance to the depressor effect of NTG. This was evident because the depressor effect of NTG (150 mu g/kg, i.v.) was almost completely abolished in the tolerant rats. The tolerance could be diminished by treatment with DMB. In the in vitro study, the exposure of aortic rings of Sprague-Dawley rats to NTG (10 mu M) for 30 min caused tolerance to the vasodilating effect of NTG. The tolerance is evident because of a substantial right shift of the NTG concentration-relaxation curves. This shift was reduced by pretreatment of the aortic rings with DMB. In cultured human umbilical vein endothelial cells (HUVECs), incubation of NTG for 16 h increased reactive oxygen species (ROS) production, attenuated cyclic guanosine monophosphate (cGMP) levels and decreased the activity of aldehyde dehydrogenase 2 (ALDH-2), the main enzyme responsible for NTG bioactivation. All the effects mentioned above were prevented by co-incubation with DMB. In conclusion, DMB prevents NTG tolerance via increasing ALDH-2 activity through decreasing ROS production.

• 出版日期2009-11
• 单位中南大学