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

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

机构地区：[1]Department of Pharmacology,School of Basic Medical Sciences,Xi'an Jiaotong University,Xi'an,710061,China [2]School of Pharmacy,Xi'an Jiaotong University Health Science Center,Xi'an,710061,China [3]Hezhou People's Hospital,Guangxi Zhuang Autonomous Region,Hezhou,Guangxi,542899,China [4]Key Laboratory of Environment and Genes Related to Diseases(Xi'an Jiaotong University),Ministry of Education,Xi'an,710061,China [5]Cardiometabolic Innovation Center,Ministry of Education,Xi'an,710061,China

出　　处：《Journal of Pharmaceutical Analysis》2024年第8期1189-1204,共16页药物分析学报（英文版）

基　　金：funded by the Fundamental Research Funds for the Central Universities(Grant No.:xzd012022099);Natural Science Basic Research Program of Shaanxi(Grant Nos.:2023-JC-ZD-47,and 2023-JC-QN-0921);Research Project of Shaanxi Administration of Traditional Chinese Medicine(Project No.:SZY-KJCYC-2023-008);Research Project of Guangxi Administration of Traditional Chinese Medicine(Project No.:GXZYJ20230711);Basic&Clinical Sciences Integration Innovation Project of Xi'an Jiaotong University(Project No.:YXJLRH2022018).

摘　　要：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.

关 键 词：GLP-1R agonist DIABETES Cognitive disorder MITOPHAGY Cell membrane chromatography 

分 类 号：R914[医药卫生—药物化学]