Demethylbellidifolin prevents nitroglycerin tolerance via improved aldehyde dehydrogenase 2 activity.

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 microg/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 microM) 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.

journal_name

Planta Med

journal_title

Planta medica

authors

Shi RZ,Li XH,Jia SJ,Fu QM,Chen YR,Chen J,Chen A,Li SX,Tan GS,Li YJ,Zhang GG

doi

10.1055/s-0029-1185774

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

1476-81

issue

14

eissn

0032-0943

issn

1439-0221

journal_volume

75

pub_type

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