The Effect And Molecular Mechanism Of Flavones From C. Tinctoria In The BCAS Model

Vascular cognitive dysfunction(VCI)has received increasing attention in the study of neurodegenerative diseases.VCI mainly refers to the chronic hypoperfusion white matter injury caused by brain tissue ischemia and accompanied by different degrees of neuroinflammation,which is mainly caused by vascular risk factors and cerebrovascular diseases.Coreopsis tinctoria Nutt.is widely distributed in.Xinjiang,and is widely recorded in Uygur ethnic medicine.It is mainly used in inflorescence,which has the functions of reducing blood pressure,regulating blood sugar,improving blood lipid and preventing cardiovascular diseases.Recent studies have shown that the extract of C.tinctoria can play a role in the intervention of diabetes through vascular protection.Our previous studies have confirmed that the total extract of flavonoids from C.tinctoria has certain neuroprotective activity,but its therapeutic effect on neurodegenerative diseases has not been systematically studied.Combined with the neuroprotective and vascular protective characteristics of C.tinctoria,this study investigated the intervention and mechanism of flavone from C.tinctoria on VCI caused by chronic hypoperfusion white matter injury.(1)Network pharmacology and in vitro experiments were used to verify that Coreopsis tinctoria can influence the function of microglia.9 main active flavonoids in Coreopsis tinctoria can exert the effect by AKT、TNF、IL6、TP53、SRC、EGFR、JUN、STAT3、MAPK3 and CTNNB1,which involve in MAPK,TNF and JAK-STAT signaling pathways.(2)BCAS(bilateral CCA stenosis)model was used to simulate chronic hypoperfusion white matter injury in VCI.Open field,new object recognition,Morris water maze,LFB and IBA staining,qRT-PCR and other experimental results confirmed that 4.5mm spring microcoil could cause the most moderate white matter injury in C57BL/6J mice.(3)Under the optimal modeling conditions,the results of open field,new object recognition experiment,Morris water maze and other behavioral experiments,LFB staining and IBA immunohistochemical staining showed that the total extract of C.tinctoria could effectively improve the learning and cognitive impairment of BCAS mice by reducing the white matter injury caused by chronic hypoperfusion.Transcriptomic analysis and qRT-PCR results confirmed that the mechanism may be related to JAKSTAT signaling pathway and cytophagocytosis,and the specific mechanisms need to be further studied.In conclusion,through network pharmacology and in vitro experiments,this study confirmed that flavones from Coreopsis tinctoria can improve neuroinflammation through microglia cells,and preliminarily explored the intervention and potential mechanism of flavones from Coreopsis tinctoria on VCI for the first time,providing a new idea for the development and utilization of Coreopsis tinctoria in neuroprotection.