Neuroprotective Effects of Salidroside in the MPTP Mouse Model of Parkinson’s Disease: Involvement of the PI3K/Akt/GSK3βPathway

Abstract

The degenerative loss through apoptosis of dopaminergic neurons in the substantia nigra pars compacta plays a primary role in the progression of Parkinson's disease (PD). Our in vitro experiments suggested that salidroside (Sal) could protect against 1-methyl-4-phenylpyridine-induced cell apoptosis in part by regulating the PI3K/Akt/GSK3β pathway. The current study aims to increase our understanding of the protective mechanisms of Sal in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine- (MPTP-) induced PD mouse model. We found that pretreatment with Sal could protect against MPTP-induced increase of the time of turning downwards and climbing down to the floor. Sal also prevented MPTP-induced decrease of locomotion frequency and the increase of the immobile time. Sal provided a protection of in MPTP-induced loss of tyrosine hydroxylase-positive neurons in SNpc and the level of DA, DOPAC, and HVA in the striatum. Furthermore, Sal could increase the phosphorylation level of Akt and GSK3β, upregulate the ratio of Bcl-2/Bax, and inhibit the activation of caspase-3, caspase-6, and caspase-9. These results show that Sal prevents the loss of dopaminergic neurons and the PI3K/Akt/GSK3β pathway signaling pathway may have mediated the protection of Sal against MPTP, suggesting that Sal may be a potential candidate in neuroprotective treatment for PD.

SIRT1 mediates salidroside‐elicited protective effects against MPP+‐induced apoptosis and oxidative stress in SH‐SY5Y cells: involvement in suppressing MAPK pathways

“…The Bcl‐2/Bax ratio is a determining factor in the regulation of apoptotic cell death (Bar‐Am et al, ). In present study, we also found that salidroside reverses MPP + ‐induced the up‐regulation of Bax/cl‐2 ratio, while this effect was blocked by sirtinol, which is consistent with the study done by Zhang et al () and the research done by Kou et al (). These results suggest that SIRT1 contributes to the neuroprotective effect of salidroside against PD in part through improving mitochondrial apoptosis.…”

Neuroprotective Effects of Salidroside on Cerebral Ischemia/Reperfusion-Induced Behavioral Impairment Involves the Dopaminergic System

“…In the present study, we found that salidroside administration induced an additional increase in dopamine and reversed the reduction of both DOPAC and HVA. These results were similar to those reported recently, in which salidroside administration increased the levels of DA, DOPAC, and HVA in the striatum of brains with neurodegenerative disease (Zhang et al, 2016;Li and Chen, 2019). Under normal conditions, the dopaminergic system maintains a steady state; however, this fine balance is affected when any factor is disrupted and consequently induces serious physiological reactions (Defaix et al, 2018;Zeiler and Menon, 2018;Dyhrfort et al, 2019).…”

“…Degenerative alterations in the ipsilateral SNpc have also been reported in clinical patients with neurodegenerative disorders (Lou et al, 2009;Nakajima et al, 2010;Robles, 2016). Several studies have demonstrated that salidroside potentially targets extracellular TH secretion in the SNpc (Zhang et al, 2016;Wu et al, 2018;Li and Chen, 2019). Indeed, our data showed a similar observation: salidroside treatment prevented dopaminergic neurons loss as displayed by the preservation of TH-positive cells in the rat SNpc.…”

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

“…Moreover, abnormal regulation of GSK-3beta can lead to the pathophysiological manifestations of PD. Some studies have suggested that GSK-3beta is abnormally expressed in PD [94][95][96].…”