Planta Med. 2000 Mar; 66(2): 114-8.

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.

Zhang YW, Morita I, Shao G, Yao XS, Murota S.

Section of Cellular Physiological Chemistry, Graduate School, Tokyo Medical and Dental University, Japan.

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.