Zhiti Zhang1, Peng Xu2, Haiyan Yu3, Lei Shi3. 1. Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng 252000, Shandong, China. 2. Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng 252000, Shandong, China. Electronic address: pengxu6600@sina.com. 3. Department of Neurology, Liaocheng People's Hospital, Liaocheng 252000, Shandong, China.
Abstract
BACKGROUND: Ischemic cerebrovascular disease (ICVD) is the third leading cause of death worldwide. Luteolin is a naturally flavonoid widely distributed in many plant leaves. This study aimed to explore the effects of luteolin on H2O2-induced ICVD cell oxidative injury model, as well as underlying molecular mechanisms. METHODS: Viability and apoptosis of PC-12 cells and rat brain microvascular endothelial cells (rBMECs) were detected using CCK-8 assay and FITC-Annexin V/PI staining, respectively. The levels of ROS and MDA were measured using DCFH-DA staining and MDA assay kit, respectively. Cell transfection was conducted to change the expression level of miR-21. Expression levels of key factors involved in cell proliferation, oxidative stress, apoptosis, PI3K/AKT and PDCD4/p21 pathways were evaluated using western blotting. RESULTS: Low concentration of luteolin had no significant effect on PC-12 cell viability and presented protective effects on H2O2-induced PC-12 cell viability loss, proliferation inhibition, ROS generation, oxidative stress increase and apoptosis. Moreover, luteolin up-regulated the expression level of miR-21 in H2O2-treated PC-12 cells. Overexpression of miR-21 strengthened the protective effects of luteolin on H2O2-induced PC-12 cell oxidative injury. Suppression of miR-21 had opposite effects. Furthermore, luteolin alleviated H2O2-induced inactivation of PI3K/AKT pathway and activation of PDCD4/p21 pathway in PC-12 cells by up-regulating miR-21. Besides, luteolin also protected rBMECs from H2O2-induced oxidative injury. CONCLUSION: Our research revealed the protective effects of luteolin on H2O2-induced ICVD cell oxidative injury. Luteolin protected PC-12 cells from H2O2-induced oxidative injury by up-regulating miR-21, activating PI3K/AKT pathway and inactivating PDCD4/p21 pathway.
BACKGROUND:Ischemic cerebrovascular disease (ICVD) is the third leading cause of death worldwide. Luteolin is a naturally flavonoid widely distributed in many plant leaves. This study aimed to explore the effects of luteolin on H2O2-induced ICVD cell oxidative injury model, as well as underlying molecular mechanisms. METHODS: Viability and apoptosis of PC-12 cells and rat brain microvascular endothelial cells (rBMECs) were detected using CCK-8 assay and FITC-Annexin V/PI staining, respectively. The levels of ROS and MDA were measured using DCFH-DA staining and MDA assay kit, respectively. Cell transfection was conducted to change the expression level of miR-21. Expression levels of key factors involved in cell proliferation, oxidative stress, apoptosis, PI3K/AKT and PDCD4/p21 pathways were evaluated using western blotting. RESULTS: Low concentration of luteolin had no significant effect on PC-12 cell viability and presented protective effects on H2O2-induced PC-12 cell viability loss, proliferation inhibition, ROS generation, oxidative stress increase and apoptosis. Moreover, luteolin up-regulated the expression level of miR-21 in H2O2-treated PC-12 cells. Overexpression of miR-21 strengthened the protective effects of luteolin on H2O2-induced PC-12 cell oxidative injury. Suppression of miR-21 had opposite effects. Furthermore, luteolin alleviated H2O2-induced inactivation of PI3K/AKT pathway and activation of PDCD4/p21 pathway in PC-12 cells by up-regulating miR-21. Besides, luteolin also protected rBMECs from H2O2-induced oxidative injury. CONCLUSION: Our research revealed the protective effects of luteolin on H2O2-induced ICVD cell oxidative injury. Luteolin protected PC-12 cells from H2O2-induced oxidative injury by up-regulating miR-21, activating PI3K/AKT pathway and inactivating PDCD4/p21 pathway.