Dioscin-Mediated Autophagy Alleviates MPP+-Induced Neuronal Degeneration: An In Vitro Parkinson’s Disease Model

Abstract

Autophagy is a cellular homeostatic process by which cells degrade and recycle their malfunctioned contents, and impairment in this process could lead to Parkinson’s disease (PD) pathogenesis. Dioscin, a steroidal saponin, has induced autophagy in several cell lines and animal models. The role of dioscin-mediated autophagy in PD remains to be investigated. Therefore, this study aims to investigate the hypothesis that dioscin-regulated autophagy and autophagy-related (ATG) proteins could protect neuronal cells in PD via reducing apoptosis and enhancing neurogenesis. In this study, the 1-methyl-4-phenylpyridinium ion (MPP+) was used to induce neurotoxicity and impair autophagic flux in a human neuroblastoma cell line (SH-SY5Y). The result showed that dioscin pre-treatment counters MPP+-mediated autophagic flux impairment and alleviates MPP+-induced apoptosis by downregulating activated caspase-3 and BCL2 associated X, apoptosis regulator (Bax) expression while increasing B-cell lymphoma 2 (Bcl-2) expression. In addition, dioscin pre-treatment was found to increase neurotrophic factors and tyrosine hydroxylase expression, suggesting that dioscin could ameliorate MPP+-induced degeneration in dopaminergic neurons and benefit the PD model. To conclude, we showed dioscin’s neuroprotective activity in neuronal SH-SY5Y cells might be partly related to its autophagy induction and suppression of the mitochondrial apoptosis pathway.

Dioscorea nipponica Makino Rhizome Extract and Its Active Compound Dioscin Protect against Neuroinflammation and Scopolamine-Induced Memory Deficits

“…Multiple studies have indicated that DNRE consists of steroidal saponin derivatives; dioscin is the most abundant among them [ 21 ]. In addition, our recent study found that dioscin ameliorates MPP + -induced neurotoxicity via autophagy [ 22 ]. We observed that dioscin substantially downregulates inflammatory enzymes iNOS and COX-2 in LPS-activated BV-2 cells.…”

“…In the ABTS analysis, dioscin showed more efficiency in free radicals scavenging than DNRE ( Figure 4 B). Previously, we showed that dioscin is a potential neuroprotector in an MPP + -induced Parkinson’s disease model [ 22 ], where dioscin showed a substantial reduction of apoptosis and upregulated neurotrophic factors such as BDNF and pCREB. Additionally, dioscin ameliorated inflammatory enzyme upregulation in LPS-stimulated in vitro model.…”

“…Based on our previous finding of dioscin-induced improvement on neurotrophic factors in neuronal cells [ 22 ], we tested dioscin’s impact on the scopolamine-induced amnesic mice model. Scopolamine is an anticholinergic drug that antagonises cholinergic receptors and impairs hippocampal and prefrontal cortex transmission that deficits learning acquisition [ 10 ].…”

“…Our previous study [ 22 ] showed that dioscin is a potential bioactive compound that enhances neurotrophic factors in neuronal cells. In corroboration to prior findings, we found that dioscin treatment improves spatial and reference memory in scopolamine-treated animal models.…”

Mitophagy: A promising therapeutic target for neuroprotection during ageing and age‐related diseases

“…Dioscin is also used to treat AD and other age‐related diseases (Zhang et al, 2020). It protects an immortalized mouse hippocampal neuronal precursor cell from Aβ 1–42 ‐induced neurotoxicity, reduces oxidative stress and inflammation in rats, and promotes autophagy (Azam et al, 2022).…”