Dioscin Protects against Aβ1-42 Oligomers-Induced Neurotoxicity via the Function of SIRT3 and Autophagy

Alzheimer's disease (AD) is a common neurodegenerative disease with high incidence among old people. Dioscin is a product extracted from natural herbs, which has multiple pharmacological activities. In this study, we investigated the potential effects of disocin on amyloid-β peptide (Aβ1-42) oligomers-treated HT22 cells. Aβ1-42 oligomers induced great neurotoxicity to HT22 cells as examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results of terminal deoxynucleoitidyl transferase-mediated deoxyuridine triphosphate biotin nich end labeling (TUNEL) staining and flow cytometry indicated that Aβ1-42 oligomers led to increased apoptosis and generation of reactive oxygen species (ROS) in HT22 cells. However, dioscin could remarkably inhibit the neurotoxicity induced by Aβ1-42 oligomers, as well as decrease the apoptosis and ROS generation. Sirtuin-3 (SIRT3) staining and quantification indicated that dioscin upregulated the expression of neuroprotective SIRT3. Moreover, dioscin induced the formation of autophagosomes and autolysosomes in HT22 cells. Dioscin also enhanced the levels of Beclin-1 and LC3-II while decreased the level of p62. These results suggested that dioscin could activate autophagy in HT22 cells. It was also found that knocking down SIRT3 resulted in the downregulation of Beclin-1, LC3-II and the aggregation of p62, suggesting that SIRT3 was an important regulator in autophagy. Furthermore, we found that knocking down SIRT3 or inhibiting autophagy suppressed the protective effects of dioscin on Aβ1-42 oligomers-induced neurotoxicity, apoptosis and ROS generation. These results revealed that SIRT3 and autophagy functioned together in the neuroprotective mechanisms of dioscin. Therefore, dioscin might be a promising drug to protect against Aβ1-42 oligomers-induced neurotoxicity and reduce neuron damage or death in AD.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:68

Enthalten in:

Chemical & pharmaceutical bulletin - 68(2020), 8 vom: 17., Seite 717-725

Sprache:

Englisch

Beteiligte Personen:

Zhang, Ze [VerfasserIn]
Han, Kun [VerfasserIn]
Wang, Chunying [VerfasserIn]
Sun, Chengyan [VerfasserIn]
Jia, Ning [VerfasserIn]

Links:

Volltext

Themen:

3B95U4OLWV
Alzheimer’s disease (AD)
Amyloid beta-Peptides
Amyloid beta-protein (1-42)
Autophagy
Beclin-1
Dioscin
Diosgenin
EC 3.5.1.-
Journal Article
K49P2K8WLX
Peptide Fragments
Protective Agents
RNA, Small Interfering
Reactive Oxygen Species
Sirtuin 3
Sirtuin-3

Anmerkungen:

Date Completed 04.02.2021

Date Revised 04.02.2021

published: Print

Citation Status MEDLINE

doi:

10.1248/cpb.c20-00046

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM313172749