Screening of anti-hypoxia/reoxygenation agents by an in vitro model. Part 1: Natural inhibitors for protein tyrosine kinase activated by hypoxia/reoxygenation in cultured human umbilical vein endothelial cells.
Protein tyrosine kinase (PTK) signaling pathways play important roles in ischemia/reperfusion (I/R) or hypoxia/reoxygenation (H/R) injuries. Inhibition of PTK activation can protect against I/R- or H/R-induced damages. As one part of our work for seeking bioactive compounds from natural sources against I/R or H/R, in the present study we examined the effects of 54 compounds purified from various traditional Chinese herbs on H/R-induced PTK activation by means of an in vitro H/R model in cultured human umbilical vein endothelial cells (HUVEC). The results demonstrated that an increase in PTK activation was induced after 2 h of reoxygenation. Compounds 2 (macrostemososide A), 3 (laxogenin-3-O-beta-D-xylopyranosyl-(1-->4)-alpha-L-arabinopyra nosyl- (1-->6)-beta-D-glucopyranoside), 4 (chinenoside II), 7 (ginsenoside-Rd), 52 (icariin), 53 (icariside), and 54 (icaritin) showed relatively obvious inhibition on this H/R-induced PTK activation. Compounds 5 (beta-sitosterol) and 6 (daucosterine), especially 5, completely blocked such an increased activation of PTK induced by H/R. On the contrary, compound 29 (isocumarine) significantly promoted PTK activation further. Moreover, the effects of these compounds on PTK activation were dose-dependent.
Zhang
Y W
YW
Section of Cellular Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, Japan.
Morita
I
I
Shao
G
G
Yao
X S
XS
Murota
S
S
D015687:Cell Hypoxia; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010477:Perfusion; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015427:Reperfusion Injury / Q000201:enzymology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D011505:Protein-Tyrosine Kinases