Physalin B Reduces Tau Phosphorylation and Cell Apoptosis in HEK293 Cells by Activating FoxO1

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BACKGROUND: Physalin B (PB) is one of the main active compounds of Solanaceae plants, with a wide range of biological activities. PB reportedly has the potential to treat Alzheimer's disease (AD).

OBJECTIVE: In this study, we investigated the effect of PB on Tau phosphorylation and cell apoptosis using Tau-expressing HEK293 cells (HEK293/Tau) as a cellular model.

METHODS: The optimum concentration of PB to treat HEK293/Tau cells was determined using the CCK-8 assay. Additionally, the expression of FoxO1, Tau-5, p-Tau (T231, S262, and S404), ERK, p-ERK, GSK-3β, and p-GSK-3β was detected using western blotting to determine the effect of PB on Tau phosphorylation. The apoptosis rate was detected using flow cytometry, and the expression of Bax and Bcl-2 was detected using western blotting and verified using real-time quantitative polymerase chain reaction (RT-qPCR). Moreover, cells were transfected with FoxO1 siRNA to downregulate FoxO1 expression, and the expression of the above-mentioned proteins was detected to verify the effect of PB on Tau phosphorylation and cell apoptosis.

RESULTS: After 24 h of PB treatment, the phosphorylation levels of Tau at S404, S262, and T231 sites decreased significantly, and the activities of GSK-3β and ERK were inhibited. PB also reduced cell apoptosis by reducing the expression of Bax and increasing the expression of Bcl-2. In addition, PB decreased Tau phosphorylation and cell apoptosis by upregulating FoxO1.

CONCLUSION: The natural compound PB exhibited a protective effect in the AD cell model by increasing FoxO1 expression and reducing Tau phosphorylation and cell apoptosis.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

2023

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:17

Enthalten in:

Current molecular pharmacology - 17(2023) vom: 24., Seite e210723218991

Sprache:

Englisch

Beteiligte Personen:

Zhang, Wei [VerfasserIn]
Shi, Yating [VerfasserIn]
Lv, Mingti [VerfasserIn]
Zhang, Yimin [VerfasserIn]
Ren, Wei [VerfasserIn]
Shi, Ruling [VerfasserIn]
Wang, Hecheng [VerfasserIn]
Shan, Linlin [VerfasserIn]

Links:

Volltext

Themen:

23133-56-4
AD cell model.
Alzheimer’s disease
Apoptosis
Bcl-2-Associated X Protein
EC 2.7.11.1
FOXO1 protein, human
FoxO1
Glycogen Synthase Kinase 3 beta
Journal Article
Physalin B
Tau Proteins
Tau phosphorylation

Anmerkungen:

Date Completed 30.11.2023

Date Revised 30.11.2023

published: Print

Citation Status MEDLINE

doi:

10.2174/1874467217666230721124057

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM359899994