The protective effects of EGb761 in endothelial cells and macrophages

• Main Authors: Jin-Yi Tsai, 蔡妗怡
• Other Authors: Tzong-shyuan Lee
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/27161805584423065987

博士 === 國立陽明大學 === 生理學研究所 === 99 === The standard leaf extract of Ginkgo biloba-EGB761, which is the most widely used in treatment of Alzheimer’s disease and prevention of hypertension or atherosclerosis. However, the underlying mechanisms of EGb761 in preventing the progression of atherosclerosis and hypertension are not fully understood. Treatment with EGb761 that was impairing oxidized low-density lipoprotein (oxLDL)-mediated cholesterol accumulation in macrophages. Consequently, EGb761 significantly down-regulated the scavenger receptor class A mRNA and protein expression via decreasing expression of activator protein 1 (AP-1); however, EGb761 increased the protein stability of ATP-binding cassette transporter A1 (ABCA1) by reducing calpain activity without affecting ABCA1 mRNA expression. Small interfering RNA (siRNA) targeting heme oxygenase-1 (HO-1) abolished the EGb761-induced protective effects on the expression of AP-1, SR-A, ABCA1, and calpain activity. Moreover, the atherosclerotic lesion size of was smaller in EGb761-treated apolipoprotein E-deficient mice compared to the vehicle-treated mice, and the expression of HO-1, SR-A, and ABCA1 in aortas was similar to that observed in macrophages. Activation of endothelial nitric oxide synthase (eNOS) is regulated by kinase-dependent signaling or physical interaction with intracellular proteins under physiological or pathological conditions. In this study, we employing pharmacological inhibition indicated that EGb761 increased NO production and phosphorylation of eNOS was via Akt and Src signaling pathways; furthermore, EGb761-increasing eNOS phosphorylation is Akt dependent but not Src. By contract, Src kinase which is mediated EGb761-decreased eNOS/caveolin-1 protein-protein interaction, but this effect is reversed by its abolition after pharmacological inhibition using PP1. These data suggest that both kinase-dependent signaling pathway and protein-protein interaction are involved in EGb761-induced eNOS activation. According these findings, we suggest that the protection effects of EGb761 in foam cell formation are regulated by a novel HO-1-dependent regulation on cholesterol homeostasis in macrophages. And the anti-hypertensive properties of EGb761 is mainly regulated the eNOS/caveolin-1 complex but not the dominate kinase depended pathways. Thus EGb761 may be a portent agent in treatment of hypertension and prevent the early stage of atherosclerosis progression.