Hyun Jung Lee, MiRan Seo, Eun Jig Lee1. 1. Severance Integrative Research Institute for Cerebral & Cardiovascular Disease, Yonsei University College of Medicine, 50Yonsei-ro, Seodaemun-gu, Seoul120-752, Korea. seo99@yuhs.ac.
Abstract
AIMS: Salvianolic acid B (Sal B), one of the most active components of Danshen extracts, has beneficial roles in the prevention and treatment of cardiovascular diseases. However, the precise mechanism by which Sal B exerts its effects on vascular cells is unclear. We aimed to elucidate the effects of Sal B on vascular cells and the underlying mechanisms. METHODS AND RESULTS: Treatment of vascular smooth muscle cells with Sal B effectively inhibited platelet-derived growth factor (PDGF)-induced cell proliferation and migration, and markedly increased heme oxygenase-1 (HO-1) expression. These changes were accompanied by antioxidant effects, including decreases in the generation of reactive oxygen species and the NADP/NADPH ratio. In human umbilical vein endothelial cells, Sal B also strongly induced HO-1 and effectively inhibited tumor necrosis factor-α-induced NF-κB activation. Knockdown of HO-1 expression by siRNA abolished the effects of Sal B in vascular cells and prevented the inhibition of proliferation, migration, and inflammation in HO-1-deficient cells. In ex vivo culture of arterial rings isolated from nuclear factor-E2-related factor 2 (Nrf2)-knockout mice, Sal B neither induce HO-1 expression and nor inhibit PDGF-induced neointimal hyperplasia in arteries, suggesting that Nrf2 plays a crucial role in the induction of HO-1 expression. CONCLUSIONS: We conclude that Sal B exerts antiatherogenic effects by inhibiting the proliferation, migration, and inflammation of vascular cells through induction of HO-1 via Nrf2 activation.
AIMS: Salvianolic acid B (Sal B), one of the most active components of Danshen extracts, has beneficial roles in the prevention and treatment of cardiovascular diseases. However, the precise mechanism by which Sal B exerts its effects on vascular cells is unclear. We aimed to elucidate the effects of Sal B on vascular cells and the underlying mechanisms. METHODS AND RESULTS: Treatment of vascular smooth muscle cells with Sal B effectively inhibited platelet-derived growth factor (PDGF)-induced cell proliferation and migration, and markedly increased heme oxygenase-1 (HO-1) expression. These changes were accompanied by antioxidant effects, including decreases in the generation of reactive oxygen species and the NADP/NADPH ratio. In human umbilical vein endothelial cells, Sal B also strongly induced HO-1 and effectively inhibited tumor necrosis factor-α-induced NF-κB activation. Knockdown of HO-1 expression by siRNA abolished the effects of Sal B in vascular cells and prevented the inhibition of proliferation, migration, and inflammation in HO-1-deficient cells. In ex vivo culture of arterial rings isolated from nuclear factor-E2-related factor 2 (Nrf2)-knockout mice, Sal B neither induce HO-1 expression and nor inhibit PDGF-induced neointimal hyperplasia in arteries, suggesting that Nrf2 plays a crucial role in the induction of HO-1 expression. CONCLUSIONS: We conclude that Sal B exerts antiatherogenic effects by inhibiting the proliferation, migration, and inflammation of vascular cells through induction of HO-1 via Nrf2 activation.
Authors: Andrew S Davison; Brendan P Norman; Gordon A Ross; Andrew T Hughes; Milad Khedr; Anna M Milan; James A Gallagher; Lakshminarayan R Ranganath Journal: JIMD Rep Date: 2019-05-31
Authors: Byung Soo Kong; Soo Jung Im; Yang Jong Lee; Yoon Hee Cho; Yu Ri Do; Jung Woo Byun; Cheol Ryong Ku; Eun Jig Lee Journal: PLoS One Date: 2016-03-22 Impact factor: 3.240