Baicalein: A potential GLP-1R agonist improves cognitive disorder of diabetes through mitophagy enhancement

Na Liu; Xin Cui; Wenhui Yan; Tingli Guo; Zhuanzhuan Wang; Xiaotong Wei; Yuzhuo Sun; Jieyun Liu; Cheng Xian; Weina Ma; Lina Chen

doi:10.1016/j.jpha.2024.100968

Volume 14 Issue 8

Aug. 2024

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Article Navigation > Journal of Pharmaceutical Analysis > 2024 > 14(8): 100968

Na Liu, Xin Cui, Wenhui Yan, Tingli Guo, Zhuanzhuan Wang, Xiaotong Wei, Yuzhuo Sun, Jieyun Liu, Cheng Xian, Weina Ma, Lina Chen. Baicalein: A potential GLP-1R agonist improves cognitive disorder of diabetes through mitophagy enhancement[J]. Journal of Pharmaceutical Analysis, 2024, 14(8): 100968. doi: 10.1016/j.jpha.2024.100968

Citation:

Na Liu, Xin Cui, Wenhui Yan, Tingli Guo, Zhuanzhuan Wang, Xiaotong Wei, Yuzhuo Sun, Jieyun Liu, Cheng Xian, Weina Ma, Lina Chen. Baicalein: A potential GLP-1R agonist improves cognitive disorder of diabetes through mitophagy enhancement[J]. Journal of Pharmaceutical Analysis, 2024, 14(8): 100968. doi: 10.1016/j.jpha.2024.100968

Citation:

Na Liu, Xin Cui, Wenhui Yan, Tingli Guo, Zhuanzhuan Wang, Xiaotong Wei, Yuzhuo Sun, Jieyun Liu, Cheng Xian, Weina Ma, Lina Chen. Baicalein: A potential GLP-1R agonist improves cognitive disorder of diabetes through mitophagy enhancement[J]. Journal of Pharmaceutical Analysis, 2024, 14(8): 100968. doi: 10.1016/j.jpha.2024.100968

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Baicalein: A potential GLP-1R agonist improves cognitive disorder of diabetes through mitophagy enhancement

doi: 10.1016/j.jpha.2024.100968

a. Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, China;
b. School of Pharmacy, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China;
c. Hezhou People's Hospital, Guangxi Zhuang Autonomous Region, Hezhou, Guangxi, 542899, China;
d. Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, 710061, China;
e. Cardiometabolic Innovation Center, Ministry of Education, Xi'an, 710061, China

Funds:

The authors thank the efforts of all the members from NLERC of Screening & Analysis for Natural Vascular Medicine Lab of Xian Jiaotong University and Biomedical Experimental Center of Xi'an Jiaotong University. Especially, Langchong He for his effort on experiment platform bulit, Shengli Han and Nan Wang for their advices and technical assistance. We also thank Hao Hu for his contribution on MWM test.

Received Date: Oct. 18, 2023
Accepted Date: Mar. 20, 2024
Rev Recd Date: Feb. 22, 2024
Publish Date: Mar. 24, 2024

Abstract

Abstract

There is increasing evidence that the activation of glucagon-like peptide-1 receptor (GLP-1R) can be used as a therapeutic intervention for cognitive disorders. Here, we have screened GLP-1R targeted compounds from Scutellaria baicalensis, which revealed baicalein is a potential GLP-1R small-molecule agonist. Mitophagy, a selective autophagy pathway for mitochondrial quality control, plays a neuroprotective role in multiple cognitive impairment diseases. We noticed that Glp1r knock-out (KO) mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze (MWM) test than their wide-type (WT) counterparts. Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice. Finally, we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1R-dependent manner. Our findings shed light on the importance of GLP-1R for cognitive function maintenance, and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis. Furthermore, we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.
- GLP-1R agonist,
- Diabetes,
- Cognitive disorder,
- Mitophagy,
- Cell membrane chromatography

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References(76)

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