Demethylbellidifolin preserves endothelial function by reduction of the endogenous nitric oxide synthase inhibitor level.
The present study examined the anti-oxidation and protective effects of demethylbellidifolin (DMB), a xanthone compound extracted from swertia davidi Franch, on endothelium. The relationship between the protective effects of DMB on endothelium and the level of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, was also determined in the present study. DMB significantly inhibited Cu(2+)-induced low-density lipoprotein (LDL) oxidation and scavenged DPPH radicals. DMB significantly attenuated the inhibition of endothelium-dependent vasodilator responses, induced by lysophosphatidycholine (LPC) in vitro and LDL in vivo, and increased release of lactate dehydrogenase induced by LDL in cultured endothelial cells. DMB significantly attenuated the increased concentration of malondialdehyde and ADMA, and the decreased level of nitric oxide induced by LDL in vivo and in cultured endothelial cells. DMB also significantly reduced the decreased activity of dimethylarginine dimethylaminohydrolase (DDAH) induced by LDL in cultured endothelial cells. In summary, the present results suggest that DMB protects endothelial damage induced by LPC in vitro and LDL in vivo or in endothelial cells, and the protective effect of DMB on the endothelium is related to reduction of ADMA concentration via an increase of DDAH activity by inhibition of lipid peroxidation.
Jiang
De-Jian
DJ
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
Jiang
Jun-Lin
JL
Zhu
Hui-Qing
HQ
Tan
Gui-Shan
GS
Liu
Shao-Qian
SQ
Xu
Kang-Ping
KP
Li
Yuan-Jian
YJ
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects; D001713:Biphenyl Compounds; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D008517:Phytotherapy; D010851:Picrates / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D029967:Swertia; D014664:Vasodilation / Q000187:drug effects; D014966:Xanthenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D010851:Picrates; D010936:Plant Extracts; D014966:Xanthenes; C467829:demethylbellidifolin; C004931:1,1-diphenyl-2-picrylhydrazyl; D019001:Nitric Oxide Synthase