J Appl Biomed 22:129-135, 2024 | DOI: 10.32725/jab.2024.015

Astragaloside IV confronts amyloid-beta-induced astrocyte senescence via hsp90aa1

Xia Yan1, Rongxiang Zeng2, Yajun Cao3, *
1 Xiangyang Hospital of Traditional Chinese Medicine (Xiangyang Institute of Traditional Chinese Medicine), Institute of Traditional Chinese Medicine, Xiangyang 441000, China
2 Foshan Hospital of Traditional Chinese Medicine, Foshan 528000, China
3 Xiangyang Hospital of Traditional Chinese Medicine (Xiangyang Institute of Traditional Chinese Medicine), Department of Anesthesiology, Xiangyang 441000, China

Cell senescence is intensively related to aging and neurodegenerative diseases. This study aimed to explore the effect and targets of Astragaloside IV against amyloid-beta-induced astrocyte senescence. Oligomerized amyloid-beta was prepared to culture with human astrocytes. The effects of Astragaloside IV were assessed based on SA-β-gal staining analysis, senescence markers (p53, p16INK4, and p21WAF1), neurotrophic growth factor levels (qRT-PCR), and cell proliferation (CCK-8 kit). The targets for Astragaloside IV were predicted, and hsp90aa1 protein was verified using molecular docking. After hsp90aa1 overexpression, the effects of Astragaloside IV on amyloid-beta-induced astrocytes were assessed. Treatment of human amyloid-beta-induced astrocytes with Astragaloside IV can decrease the percentage of SA-β-gal positive cells, downregulate the p53, p16INK4, and p21WAF1 levels, and increase the levels of neurotrophic growth factors (IGF-1 and NGF mRNA) and cell proliferation. Based on target prediction, hsp90aa1 was found to be a potential target of Astragaloside IV. Moreover, cellular experiments demonstrated that exogenously enhanced expression of hsp90aa1 overexpression suppressed the protective effect of Astragaloside IV on amyloid-beta-induced human astrocytes. The results presented here demonstrate that Astragaloside IV could confront amyloid-beta-induced astrocyte senescence via hsp90aa1, possibly opening new therapeutic avenues.

Keywords: Amyloid-beta; Astragaloside IV; Astrocyte; Heat shock protein HSP 90-alpha; Senescence
Grants and funding:

This work was supported by the National TCM Specialty Technology Inheritance Talent Training Project (Grant numbers: 20184828005) and 2019 Xiangyang Key Science and Technology Program Project (Grant numbers: 2019YL05).

Conflicts of interest:

The authors have no conflict of interest to declare.

Received: February 3, 2024; Revised: May 28, 2024; Accepted: June 21, 2024; Prepublished online: August 6, 2024; Published: September 26, 2024  Show citation

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Yan X, Zeng R, Cao Y. Astragaloside IV confronts amyloid-beta-induced astrocyte senescence via hsp90aa1. J Appl Biomed. 2024;22(3):129-135. doi: 10.32725/jab.2024.015. PubMed PMID: 39434509.
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