Salidroside Suppresses HUVECs Cell Injury Induced by Oxidative Stress through Activating the Nrf2 Signaling Pathway

Abstract

Abstract:Oxidative stress plays an important role in the pathogenesis of cardiovascular diseases. Salidroside (SAL), one of the main effective constituents of Rhodiola rosea, has been reported to suppress oxidative stress-induced cardiomyocyte injury and necrosis by promoting transcription of nuclear factor E2-related factor 2 (Nrf2)-regulated genes such as heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase (quinone1) (NQO1). However, it has not been indicated whether SAL might ameliorate endothelial injury induced by oxidative stress. Here, our study demonstrated that SAL might suppress HUVEC cell injury induced by oxidative stress through activating the Nrf2 signaling pathway. The results of our study indicated that SAL decreased the levels of intercellular reactive oxygen species (ROS) and malondialdehyde (MDA), and improved the activities of superoxide dismutase (SOD) and catalase (CAT), resulting in protective effects against oxidative stress-induced cell damage in HUVECs. It suppressed oxidative stress damage by inducing Nrf2 nuclear translocation and activating the expression of Nrf2-regulated antioxidant enzyme genes such as HO-1 and NQO1 in HUVECs. Knockdown of Nrf2 with siRNA abolished the cytoprotective effects against oxidative stress, decreased the expression of Nrf2, HO-1, and NQO1, and inhibited the nucleus translocation of Nrf2 in HUVECs. This study is the first to demonstrate that SAL suppresses HUVECs cell injury induced by oxidative stress through activating the Nrf2 signaling pathway.

Salidroside Protection Against Oxidative Stress Injury Through the Wnt/β-Catenin Signaling Pathway in Rats with Parkinson’s Disease

“…SDS exhibits a wide spectrum of pharmacological effects [9], including anti-oxidative, anti-fatigue, anti-cancer, anti-apoptosis, and anti-inflammatory effects [10]. In addition, SDS has been shown to have cytoprotective and angiogenic effects on human bone marrow-derived endothelial progenitor cells through the Akt/mammalian target of rapamycin (mTOR)/p70S6K/MAPK signaling pathways [11]. As a key molecular pathway, the Wnt/β-catenin signaling pathway regulates neuronal survival and development of the central nervous system [12].…”

MicroRNA‑21 mediates the protective effects of salidroside against hypoxia/reoxygenation‑induced myocardial oxidative stress and inflammatory response

“…Accumulating evidence has shown that ROS are the major initiators of myocardial damage in myocardial I/R injury and the attenuation of oxidative stress in myocardial cell has been demonstrated to improve myocardial function following ischemia (4,33). It has been demonstrated that salidroside may suppress oxidative stress-induced endothelial dysfunction, cardiomyocyte injury and necrosis, and cerebral ischemia/reperfusion injury, through decreasing excessive ROS generation and improving mitochondrial function (34)(35)(36)(37). However, the effect of salidroside in myocardial I/R injury-induced oxidative stress has not been studied.…”

Sulodexide up-regulates glutathione S-transferase P1 by enhancing Nrf2 expression and translocation in human umbilical vein endothelial cells injured by oxygen glucose deprivation

“…In resting cells, Nrf2 is rapidly degraded in the cytosol through the ubiquitin-proteasome system [27]. When the endothelial cells are exposed to various antioxidants, the Nrf2-Keap1 interaction is disturbed, thus preventing proteasome-dependent degradation, allowing the nuclear accumulation of Nrf2 and activating the expression of cytoprotective genes [27][28][29]. It should be stressed that, even though the most described mechanism for pharmacological activation of Nrf2 is focused on proteasome inhibition, the tight control of Nrf2 level and activity involves not only proteasomal degradation but also transcription, translation and post-translational modifications [27].…”