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DOI: 10.1055/s-0029-1185774
© Georg Thieme Verlag KG Stuttgart · New York
Demethylbellidifolin Prevents Nitroglycerin Tolerance via Improved Aldehyde Dehydrogenase 2 Activity
Publication History
received Dec. 11, 2008
revised April 27, 2009
accepted April 29, 2009
Publication Date:
16 June 2009 (online)
![](https://www.thieme-connect.de/media/plantamedica/200914/lookinside/thumbnails/10.1055-s-0029-1185774-1.jpg)
Abstract
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 µg/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 µM) 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.
Key words
demethylbellidifolin - nitroglycerin tolerance - reactive oxygen species - aldehyde dehydrogenase 2
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Prof. Dr. Guo-Gang Zhang
Department of Cardiovascular Medicine
Xiangya Hospital
Central South University
Changsha
410008 Hunan
People's Republic of China
Phone: + 86 73 14 32 76 95
Fax: + 86 73 14 32 76 95
Email: Guo_gangzhang@yahoo.cn