Ginkgo Biloba extract, via upregulation of heme oxygenase‐1, confers protection from oxidative stress‐related apoptosis induced by cigarette smoke extract in human lung endothelial cells

Abstract

We investigated the cytoprotective effects and therapeutic mechanisms of Ginkgo Biloba extract (EGb) against apoptosis of human pulmonary artery endothelial cells (HPAECs) induced by cigarette smoke extract (CSE). Challenge of CSE (160 microgram/ml) caused reduction in cell viability, increases in reactive oxygen species (ROS) and promotion of caspase‐dependant apoptosis in HPAECs, all of which were alleviated by pretreatment with EGb (100 microgram/ml). Exposure of HPAECs to EGb alone produced activation of mitogen‐activated protein kinases (MAPKs), increase in nuclear level of transcription factor Nrf2 and upregulation of heme oxygenase‐1 (HO‐1, an oxidative stress‐responsive protein). This HO‐1 upregulation was eliminated by inhibitors of MAPKs. While gene knockdown by small interfering RNAs targeting HO‐1 prevented the EGb‐induced HO‐1 upregulation, it also abolished the antioxidant, anti‐apoptotic and cytoprotective effects of EGb in HPAECs challenged with CSE. We conclude that EGb confers protection from oxidative stress–related apoptosis induced by CSE in HPAECs and its antioxidant and anti‐apoptotic effects are mediated through upregulation of HO‐1. (Supported by NSC‐95‐2320‐B‐010‐025‐MY3).