Salidroside attenuates oxidized low‑density lipoprotein‑induced endothelial cell injury via promotion of the AMPK/SIRT1 pathway

Abstract

Oxidized low-density lipoprotein (ox-LDL)-induced endothelial damage contributes to the initiation and pathogenesis of atherosclerosis. Salidroside can alleviate atherosclerosis and attenuate endothelial cell injury induced by ox-LDL. However, the mechanisms involved in this process are not fully understood. Therefore, the purpose of the present study was to investigate the role of the adenosine monophosphate-activated protein kinase (AMPK)/sirtuin (SIRT)1 pathway in the protection of salidroside against ox-LDL-induced human umbilical vein endothelial cells (HUVECs) injuries. The results revealed that salidroside reverses ox-LDL-induced HUVECs injury as demonstrated by the upregulation of cell viability and downregulation of LDH release. In addition, salidroside increased the expression of the SIRT1 protein in ox-LDL-treated HUVECs. Next, it was demonstrated that SIRT1 knockdown induced by transfection with small interfering (si)RNA targeting SIRT1 (siSRT1) abolished the protection of salidroside against ox-LDL-induced HUVECs injuries. This was illustrated by a decrease in cell viability and an increase in LDH release, caspase-3 activity and apoptosis rate. Furthermore, salidroside mitigated ox-LDL-induced reactive oxygen species production, upregulated malondialdehyde content and NADPH oxidase 2 expression and decreased superoxide dismutase and glutathione peroxidase activities, while these effects were also reversed by siSIRT1 transfection. In addition, it was demonstrated that salidroside suppressed ox-LDL-induced mitochondrial dysfunction as demonstrated by the increase in mitochondrial membrane potential and decreases in cytochrome c expression, and Bax/Bcl-2 reductions. However, these effects were eliminated by SIRT1 knockdown. Finally, it was demonstrated that salidroside significantly upregulated the phosphorylated-AMPK expression in ox-LDL-treated HUVECs and AMPK knockdown induced by transfection with AMPK siRNA (siAMPK) leads to elimination of the salidroside-induced increase in cell viability and the decrease in LDH release. Notably, siAMPK transfection further decreased the expression of SIRT1. In conclusion, these results suggested that salidroside protects HUVECs against ox-LDL injury through inhibiting oxidative stress and improving mitochondrial dysfunction, which were dependent on activating the AMPK/SIRT1 pathway.

MicroRNA‑217 inhibition relieves cerebral ischemia/reperfusion injury by targeting SIRT1

“…additionally, activation of the aMPK/SirT1 pathway protected Pc12 cells against cisplatin-induced neurotoxicity (40). The pathway has also been reported to relieve oxidized low-density lipoprotein-induced endothelial cell injury (41). These results indicated that aMPK/SirT1 signaling serves important roles in cell injury and inflammation regulation.…”

Notoginseng Leaf Triterpenes Ameliorates OGD/R-Induced Neuronal Injury via SIRT1/2/3-Foxo3a-MnSOD/PGC-1α Signaling Pathways Mediated by the NAMPT-NAD Pathway

“…The results showed that as cells were exposed to the OGD for 3-7 h periods then followed by 24 h of reperfusion, and cell viability has a time-dependent reduction, which reached 55% following 5 h of OGD ( Figure 1(a) , P < 0.01 versus control group); after exposure of OGD for 4 h, the cell viability was partially improved along with the reperfusion time ( Figure 1(b) and 1(c) , P < 0.01). However, with OGD for 6 h, the cell viability partially decreased and aggravated ( Figure 1(b) – 1(d) , P < 0.01), indicating that the 5 h of OGD treatment may be the critical point for human neurons to resist ischemic injury [ 28 , 43 ]. Hence, the 4 h OGD treatment was used as the conditions of subsequent experiments.…”

“…And then ATP synthesis was inhibited [ 11 , 18 , 23 ]. Thus, the absence of the mitochondrial NAD+ pool causes oxidative damages and excessive ROS production [ 28 , 50 , 52 ], which aggravates mitochondria impairment, including the function of mitochondria structure, depletion of ATP production, and depolarization of MMP [ 12 , 13 ]. In our study, the results showed after OGD/R induction, the NAD+ and the ratio of NAD+/NADH level significantly decreased ( Figure 4 ), the oxidative injuries increased ( Figure 3 ) in vitro , and MMP depolarized, which was consistent with the previous reports.…”

“…NAMPT is critically involved in the regulation of such forms of cell death as apoptosis [ 20 , 24 ] and necroptosis [ 23 , 25 ] via connecting to sirtuin (SIRT) signaling [ 18 , 23 ], which constitutes a robust endogenous defense system against various stresses. On the other hand, NAMPT plays a dual role in redox metabolism and biological signaling via the NAMPT-NAD+ biosynthesis pathway [ 8 , 10 ], which is tightly associated with mitochondrial functions [ 19 , 20 , 24 ], AMPK signaling activation [ 26 – 28 ], and SIRT deacetylase activity alterations under ischemia stress [ 18 , 26 ]. All of these reports suggest that NAMPT is a crucial target for the prevention and treatment of CIS.…”

Salidroside inhibits MAPK, NF-κB, and STAT3 pathways in psoriasis-associated oxidative stress via SIRT1 activation

“…It has also been reported to protect human umbilical vein endothelial cells (HUVECs) from oxidative stress induced by ox-LDL through increasing SIRT1, FoxO1, and SOD expression and to simultaneously down-regulate MDA and LDH [69]. Meanwhile, another research concluded that salidroside protects HUVECs against ox-LDL injury through inhibiting oxidative stress and improving mitochondrial dysfunction, which were dependent on AMPK/SIRT1 pathway activation [70]. Furthermore, Xu N et al concluded that salidroside decreased the expression of inflammatory cytokines and improved LPS-induced learning memory impairments, which were involved in the SIRT1dependent Nrf-2/HO-1/NF-κB pathway [71].…”