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.

BackgroundDue to the lack of strong evidence to identify the relationship between antihypertensive drugs use and the risk of prostate cancer, it was needed to do a systematic review to go into the subject.MethodsWe systematically searched PubMed, Web of Science and Embase to identify studies published, through May 2015. Two evaluators independently reviewed and selected articles involving the subject. We used the Newcastle-Ottawa Scale (NOS) to assess the quality of the studies. All extracted results to evaluate the relationship between antihypertensive drugs usage and prostate cancer risk were pool-analysed using Stata 12.0 software.ResultsA total of 12 cohort and 9 case-control studies were ultimately included in our review. Most of the studies were evaluated to be of high quality. There was no significant relationship between angiotensin converting enzyme inhibitors (ACEI) usage and the risk of prostate cancer (RR 1.07, 95% CI 0.96–1.20), according to the total pool-analysed. Use of angiotensin receptor blocker (ARB) was not associated with the risk of prostate cancer (RR 1.09, 95% CI 0.97–1.21), while use of CCB may well increase prostate cancer risk based on the total pool-analysed (RR 1.08, 95% CI 1–1.16). Moreover, subgroup analysis suggested that use of CCB clearly increased prostate cancer risk (RR 1.10, 95% CI 1.04–1.16) in terms of case-control studies. There was also no significant relationship between use of diuretic (RR 1.09, 95% CI 0.95–1.25) or antiadrenergic agents (RR 1.22, 95% CI 0.76–1.96) and prostate cancer risk.ConclusionsThere is no significant relationship between the use of antihypertensive drugs (ACEI, ARB, beta-blockers and diuretics) and prostate cancer risk, but CCB may well increase prostate cancer risk, according to existing observational studies.Electronic supplementary materialThe online version of this article (10.1186/s12894-018-0318-7) contains supplementary material, which is available to authorized users.

Parkinson’s disease (PD) is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and the presence of Lewy bodies (LBs) in the surviving SNc neurons. LBs formation is caused by the accumulation of α-synuclein (α-syn) or phosphorylated α-syn at serine-129 (pSer129-α-syn), which is implicated in the pathological progression of PD. Salidroside (Sal), the main active ingredient of the root of Rhodiola rosea L., has been reported to have potent neuroprotective properties in our previous investigations. Here, we investigated the effects of Sal on 6-OHDA and overexpresssion of WT/A30P-α-syn-induced pathological α-syn increase and the mechanism behind it in SH-SY5Y cells. We found Sal displays neuroprotective effects against 6-hydroxydopamine (6-OHDA)-induced cytotoxicity. Sal decreased the pSer129-α-syn level mainly by maintaining the normal function of ubiquitin-proteasome system (UPS). Furthermore, Sal promoted the clearance of α-syn and protected the cell viability mainly through recovered the 20S proteasome activity in WT/A30P-α-syn-transfected cells. These data provide new mechanistic insights into the neuroprotective effects of Sal and Sal may be a promising therapy to slow neurodegeneration in PD.Highlights: Sal protects cells and decreases the pSer129-α-syn protein level in 6-OHDA-induced impairmental and dysfunctional SH-SY5Y cells.Sal promotes the clearance of α-syn and protects the cell viability mainly through recovering the 20S proteasome activity in WT/A30P-α-syn plasmids transfected cells.Maintaining the normal function of the UPS may be one of the important mechanisms of Sal in neuroprotective effects.