Mechanism of astragaloside Ⅳ in regulating autophagy of PC12 cells under oxygen-glucose deprivation by medicating Akt/mTOR/HIF-1α pathway.
10.19540/j.cnki.cjcmm.20230630.402
- Author:
Jia-Xin LONG
1
;
Meng-Zhi TIAN
1
;
Xiao-Yi CHEN
1
;
Yu XIONG
2
;
Huang-He YU
1
;
Yong-Zhen GONG
1
;
Huang DING
1
;
Ming-Xia XIE
1
;
Ke DU
1
Author Information
1. Hunan University of Chinese Medicine Changsha 410208, China Laboratory of Pharmacology, Hunan University of Chinese Medicine Changsha 410208, China.
2. Hunan University of Chinese Medicine Changsha 410208, China Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese Medicine Changsha 410208, China.
- Publication Type:Journal Article
- Keywords:
Akt/mTOR/HIF-1α;
astragaloside Ⅳ(AS-Ⅳ);
autophagic injury;
oxygen-glucose deprivation(OGD)
- MeSH:
Rats;
Animals;
PC12 Cells;
Proto-Oncogene Proteins c-akt/genetics*;
Glucose/therapeutic use*;
Oxygen/metabolism*;
Beclin-1/pharmacology*;
TOR Serine-Threonine Kinases/metabolism*;
Autophagy;
Apoptosis;
Reperfusion Injury/drug therapy*
- From:
China Journal of Chinese Materia Medica
2023;48(19):5271-5277
- CountryChina
- Language:Chinese
-
Abstract:
This study explored the protective effect of astragaloside Ⅳ(AS-Ⅳ) on oxygen-glucose deprivation(OGD)-induced autophagic injury in PC12 cells and its underlying mechanism. An OGD-induced autophagic injury model in vitro was established in PC12 cells. The cells were divided into a normal group, an OGD group, low-, medium-, and high-dose AS-Ⅳ groups, and a positive drug dexmedetomidine(DEX) group. Cell viability was measured using the MTT assay. Transmission electron microscopy was used to observe autophagosomes and autolysosomes, and the MDC staining method was used to assess the fluorescence intensity of autophagosomes. Western blot was conducted to determine the relative expression levels of functional proteins LC3-Ⅱ/LC3-Ⅰ, Beclin1, p-Akt/Akt, p-mTOR/mTOR, and HIF-1α. Compared with the normal group, the OGD group exhibited a significant decrease in cell viability(P<0.01), an increase in autophagosomes(P<0.01), enhanced fluorescence intensity of autophagosomes(P<0.01), up-regulated Beclin1, LC3-Ⅱ/LC3-Ⅰ, and HIF-1α(P<0.05 or P<0.01), and down-regulated p-Akt/Akt and p-mTOR/mTOR(P<0.05 or P<0.01). Compared with the OGD group, the low-and medium-dose AS-Ⅳ groups and the DEX group showed a significant increase in cell viability(P<0.01), decreased autophagosomes(P<0.01), weakened fluorescence intensity of autophagosomes(P<0.01), down-regulated Beclin1, LC3-Ⅱ/LC3-Ⅰ, and HIF-1α(P<0.05 or P<0.01), and up-regulated p-Akt/Akt and p-mTOR/mTOR(P<0.01). AS-Ⅳ at low and medium doses exerted a protective effect against OGD-induced autophagic injury in PC12 cells by activating the Akt/mTOR pathway, subsequently influencing HIF-1α. The high-dose AS-Ⅳ group did not show a statistically significant difference compared with the OGD group. This study provides a certain target reference for the prevention and treatment of OGD-induced cellular autophagic injury by AS-Ⅳ and accumulates laboratory data for the secondary development of Astragali Radix and AS-Ⅳ.
