Abstract | ETHNOPHARMACOLOGICAL RELEVANCE: AIM OF THE STUDY: We investigated the protective effect and mechanism of GB on Glu-induced astrocytes injury. METHODS: Astrocytes were randomly divided into the control group, Glu group, GB group, and GB + IWP-4 group.The CCK-8 assay was used to determine relative cell viability in vitro. Furthermore, RNA sequencing ( RNA-seq) was performed to assess the preventive effects of GB in the Glu-induced astrocyte model and reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to validate the possible molecular mechanisms. The effects of GB on the Glu transporter and Glu-induced apoptosis of astrocytes were studied by RT-qPCR and western blot. RESULTS: GB attenuated Glu-induced apoptosis in a concentration-dependent manner, while the Wnt inhibitor IWP-4 reversed the protective effect of GB on astrocytes. The RNA-seq results revealed 4,032 differential gene expression profiles; 3,491 genes were up-regulated, and 543 genes were down-regulated in the GB group compared with the Glu group. Differentially expressed genes involved in a variety of signaling pathways, including the Hippo and Wnt pathways have been associated with the development and progression of AD. RT-qPCR was used to validate 14 key genes, and the results were consistent with the RNA-seq data. IWP-4 inhibited the regulation of GB, disturbed the apoptosis protective effect on astrocytes, and promoted Glu transporter gene and protein expression caused by Glu. CONCLUSION: Our findings demonstrate that GB may play a protective role in Glu-induced astrocyte injury by regulating the Hippo and Wnt pathways. GB was closely associated with the Wnt pathway by promoting expression of the Glu transporter and inhibiting Glu-induced injury in astrocytes.
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Authors | Jing Wang, Linwu Zhuang, Yan Ding, Zhenzhong Wang, Wei Xiao, Jingbo Zhu |
Journal | Journal of ethnopharmacology
(J Ethnopharmacol)
Vol. 270
Pg. 113807
(Apr 24 2021)
ISSN: 1872-7573 [Electronic] Ireland |
PMID | 33450290
(Publication Type: Journal Article)
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Copyright | Copyright © 2021 Elsevier B.V. All rights reserved. |
Chemical References |
- Ginkgolides
- Lactones
- Neuroprotective Agents
- Wnt Proteins
- Glutamic Acid
- ginkgolide B
- Stk3 protein, rat
- Protein Serine-Threonine Kinases
- Serine-Threonine Kinase 3
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Topics |
- Animals
- Apoptosis
(drug effects)
- Astrocytes
(cytology, drug effects)
- Cell Survival
(drug effects)
- Gene Expression Regulation
(drug effects)
- Ginkgolides
(pharmacology)
- Glutamic Acid
(toxicity)
- Lactones
(pharmacology)
- Neuroprotective Agents
(pharmacology)
- Primary Cell Culture
- Protein Serine-Threonine Kinases
(metabolism)
- Rats
- Sequence Analysis, RNA
(methods)
- Serine-Threonine Kinase 3
- Signal Transduction
(drug effects)
- Wnt Proteins
(antagonists & inhibitors, metabolism)
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