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 is chemia/reperfusion (I/R) or hypoxia/reoxygenation (H/R) injuries. Inhibitio n 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 agai nst I/R or H/R, in the present study we examined the effects of 54 compound s purified from various traditional Chinese herbs on H/R-induced PTK activa tion by means of an in vitro H/R model in cultured human umbilical vein end othelial cells (HUVEC). The results demonstrated that an increase in PTK ac tivation was induced after 2 h of reoxygenation. Compounds 2 (macrostemosos ide 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 obv ious inhibition on this H/R-induced PTK activation. Compounds 5 (beta-sitos terol) and 6 (daucosterine), especially 5, completely blocked such an incre ased activation of PTK induced by H/R. On the contrary, compound 29 (isocum arine) significantly promoted PTK activation further. Moreover, the effects of these compounds on PTK activation were dose-dependent.