Abstract
Echinacoside (ECH), the major active constituent of Cistanche deserticola, was found to exert neuroprotection through neurotrophic and anti-inflammatory functions in Parkinson’s disease (PD) models. However, a clear intermediate molecule or pathway that unifies these two effects has to be found. In this study, our results demonstrate that ECH can protect DA neurons in PD mice with Western blot and immunohistochemistry staining. The quantitative real-time polymerase chain reaction was adapted to confirm its anti-inflammatory function with decreased cytokines (interleukin- (IL-) 6, IL-1β, and TNF-α) in PD mice and LPS-induced BV2 cells. Further studies found that ECH inhibited the IL-6/JAK2/STAT3 pathway and decreased phosphorylation of STAT3 on tyr705 by Western blot. It can also increase p-STAT3 (ser727) and brain-derived neurotrophic factor (BDNF) expression in PD mice and LPS-induced BV2 cells. This study revealed that ECH exerts neurotrophic and anti-inflammatory effects by regulating the IL-6/JAK2/STAT3 pathway and the phosphorylation of STAT3, promoting the mutually beneficial influence of the two effects to maximize its neuroprotective function.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disease, and its most prominent pathological features are the progressive loss of dopaminergic (DA) neurons in substantia nigra (SN) and the Lewy body formed by misfolded α-synuclein (Poewe et al, 2017)
We examined the impact of ECH on IL-6/JAK2/STAT3 signaling in LPS-induced BV2 cells
The movement disorder society’s (MDS) clinical diagnostic criteria for PD clearly stated in its report that bradykinesia was the only critical symptom of PD in 2015 (Postuma et al, 2015), suggesting that the “kidney-qi deficiency” associated with bradykinesia could be pivotal to the pathogenesis of PD
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disease, and its most prominent pathological features are the progressive loss of dopaminergic (DA) neurons in substantia nigra (SN) and the Lewy body formed by misfolded α-synuclein (Poewe et al, 2017). ECH inhibits the phosphorylation of STAT3 on tyrosine 705 (tyr705) in the LPStreated rat intestinal epithelial cells (Li et al, 2018a) Both the local knockdown of STAT3 and inhibition of JAK2/STAT3 (tyr705) can restrain acetylated histone 3 (ac-H3) and ac-H4 levels on the promoter of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3 (NLRP3) and decrease the expression of NLRP3 (Zhu et al, 2021), whose activation can be alleviated by ECH (Zhou et al, 2020). Given these outstanding findings, we hypothesized that ECH’s neuroprotective role is intertwined with the IL-6/JAK2/STAT3 pathway and explored the hypothesis
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