Salidroside Ameliorates Mitochondria-Dependent Neuronal Apoptosis after Spinal Cord Ischemia-Reperfusion Injury Partially through Inhibiting Oxidative Stress and Promoting Mitophagy

Abstract

Ischemia-reperfusion injury is the second most common injury of the spinal cord and has the risk of neurological dysfunction and paralysis, which can seriously affect patient quality of life. Salidroside (Sal) is an active ingredient extracted from Herba Cistanche with a variety of biological attributes such as antioxidant, antiapoptotic, and neuroprotective activities. Moreover, Sal has shown a protective effect in ischemia-reperfusion injury of the liver, heart, and brain, but its effect in ischemia-reperfusion injury of the spinal cord has not been elucidated. Here, we demonstrated for the first time that Sal pretreatment can significantly improve functional recovery in mice after spinal cord ischemia-reperfusion injury and significantly inhibit the apoptosis of neurons both in vivo and in vitro. Neurons have a high metabolic rate, and consequently, mitochondria, as the main energy-supplying suborganelles, become the main injury site of spinal cord ischemia-reperfusion injury. Mitochondrial pathway-dependent neuronal apoptosis is increasingly confirmed by researchers; therefore, Sal’s effect on mitochondria naturally attracted our attention. By means of a range of experiments both in vivo and in vitro, we found that Sal can reduce reactive oxygen species production through antioxidant stress to reduce mitochondrial permeability and mitochondrial damage, and it can also enhance the PINK1-Parkin signaling pathway and promote mitophagy to eliminate damaged mitochondria. In conclusion, our results show that Sal is beneficial to the protection of spinal cord neurons after ischemia-reperfusion injury, mainly by reducing apoptosis associated with the mitochondrial-dependent pathway, among which Sal’s antioxidant and autophagy-promoting properties play an important role.

c-MYC-induced long noncoding RNA MEG3 aggravates kidney ischemia–reperfusion injury through activating mitophagy by upregulation of RTKN to trigger the Wnt/β-catenin pathway

“…Cellular stresses, including hypoxia, ischemia, and glucose deprivation, can cause damage or dysfunction of mitochondria 7 . In addition, researches showed that mitophagy exerts a protective function in the liver 8 . Mitophagy, a complex process that rapidly and selectively removes long-lived or damaged mitochondria in an autophagy-dependent manner, is an adaptive response of mitochondria to various stress damages, which was previously identified to play an important role in IRI 9 .…”

[Retracted] Insight into the Protective Effect of Salidroside against H2O2‐Induced Injury in H9C2 Cells

“…In particular, excessive ROS induce cardiomyocyte apoptosis and then lead to abnormal cardiomyocyte death, which may be one of the important reasons why cardiac hypertrophy progresses to heart failure [ 2 ]. Although salidroside exhibits the protective effect against oxidative stress [ 18 , 19 ], the mechanisms remain unclear. In this research, H9C2 cells derived from embryonic rat heart tissue were exposed to H 2 O 2 in vitro to establish a cell injury model.…”

Calcium Ions Aggravate Alzheimer’s Disease Through the Aberrant Activation of Neuronal Networks, Leading to Synaptic and Cognitive Deficits

“…Without affecting ER stress, curcumin protects mitochondria from oxidative damage by attenuating the apoptosis of cortical neurons (Zhu et al, 2004 ). In primary cultured spinal neurons, salidroside (Sal) treatment decreases apoptosis by activating PINK-Parkin pathways, leading to mitophagy of mitochondria (Gu et al, 2020 ). Similar to its effects on AD, Aβ 1–42 induces neuronal apoptosis by concurrently upregulating mitochondrial fission protein dynamin-related protein 1 (Drp1) and downregulating mitofusin 1/2 (Mfn1/2) and dynamin-like GTPase (OPA-1) in primary cultures of mouse cerebral cortical neurons (Han et al, 2017 ).…”