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.

Biotechnology and Phytochemistry of Gentianella Species from the Central Regions of the Balkan Peninsula

“…The xanthones, bellidifolin, and demethylbellidifolin, isolated from Gentianella acuta (Lv and Li 2009), showed cardiovascular protective and antitumor effects (Jiang et al 2006;Shi et al 2009;Hirakawa et al 2005). These xanthones were shown to be selective inhibitors of monoamine oxidases A (Tovilović et al 2005).…”

Validated LC–MS/MS method for quantitation of demethylbellidifolin in rat plasma and its application to pharmacokinetic and bioavailability studies

“…Demethylbellidifolin was also reported to inhibit hepatic stellate cell growth and activation, which may be related to alleviating TGF‐ β 1‐CTGF signaling response via activating PPAR‐ γ (Li, Lu, & Zou, ). In addition to the properties mentioned above, demethylbellidifolin has been reported to have many other beneficial pharmacological effects, including antioxidation, anti‐inflammation, anti‐fibrosis and cardiovascular protection effects (Jiang et al, ; Shi et al, ; Xiang et al, ; Xiao, Sun, & Zhou, ). Clearly, it is of interest to further evaluate the pharmacokinetics of demethylbellidifolin to explore its medicinal potential.…”

Characterization and Evaluation of Binding Properties of Salvianolic Acid a Imprinted Polymers Prepared by Precipitation Polymerization

“…Salvianolic acid A (Sal A) is one of main effective, water-soluble phenolic acids isolated from Danshen, which is dried root of Salivia miltiorrhiza Bge and has been widely used in traditional Chinese medicines for cardiovascular and cerebrovascular diseases [1]. It is often used to treat the diseases of blood vessels of the heart and cerebra and is very likely to become the ideal medicine for anti-cerebral ischemia.…”