Baicalein:A potential GLP-1R agonist improves cognitive disorder of diabetes through mitophagy enhancementOA
Baicalein:A potential GLP-1R agonist improves cognitive disorder of diabetes through mitophagy enhancement
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-1 R targeted com-pounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1 R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuro-protective 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-1 R-dependent manner.Our findings shed light on the importance of GLP-1 R 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.
Na Liu;Weina Ma;Lina Chen;Xin Cui;Wenhui Yan;Tingli Guo;Zhuanzhuan Wang;Xiaotong Wei;Yuzhuo Sun;Jieyun Liu;Cheng Xian
Department of Pharmacology,School of Basic Medical Sciences,Xi'an Jiaotong University,Xi'an,710061,ChinaSchool of Pharmacy,Xi'an Jiaotong University Health Science Center,Xi'an,710061,ChinaDepartment of Pharmacology,School of Basic Medical Sciences,Xi'an Jiaotong University,Xi'an,710061,China||Key Laboratory of Environment and Genes Related to Diseases(Xi'an Jiaotong University),Ministry of Education,Xi'an,710061,China||Cardiometabolic Innovation Center,Ministry of Education,Xi'an,710061,ChinaHezhou People's Hospital,Guangxi Zhuang Autonomous Region,Hezhou,Guangxi,542899,China
GLP-1R agonistDiabetesCognitive disorderMitophagyCell membrane chromatography
《药物分析学报（英文）》 2024 (008)
1189-1204 / 16
This work was funded by the Fundamental Research Funds for the Central Universities(Grant No.:xzd012022099),Natural Sci-ence Basic Research Program of Shaanxi(Grant Nos.:2023-JC-ZD-47,and 2023-JC-QN-0921),Research Project of Shaanxi Adminis-tration of Traditional Chinese Medicine(Project No.:SZY-KJCYC-2023-008),Research Project of Guangxi Administration of Tradi-tional Chinese Medicine(Project No.:GXZYJ20230711),and Basic &Clinical Sciences Integration Innovation Project of Xi'an Jiaotong University(Project No.:YXJLRH2022018).
评论