Integration of single-cell RNA sequencing and network disturbance to elucidate cross-talk between multi-components drug and trigeminal ganglia cells in migraine / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To clarify the mecha-nism of Tou Tong Ning capsule(TTNC)and elu-cidate crosstalk between multi-components drug and trigeminal ganglia cells in migraine.METH-ODS We integrated single-cell RNA sequencing data and a quantitative evaluation algorithm of the disturbance of multi-target drugs on the dis-ease network to explore the specific pathology of TTNC for migraine.Cerebrovascular smooth muscle spasmolytic activity experiment was car-ried out to verify the results of bioinformatics analysis.RESULTS TTNC can effectively regu-late the functions of synaptic signaling,inflamma-tion and immune response,and cerebrovascular smooth muscle.For different cell subtypes of tri-geminal ganglia,TTNC can significantly disturb the robustness on neuronal cell networks and non-neural networks(fibroblast and vascular cells),indicating TTNC vasodilation activity of brain vessels and neural regulation activities of various neuro types.Contraction of cerebrovas-cular smooth muscle of mouse ex vivo confirmed the vasodilation activity of TTNC and active com-pounds(Emodin,Luteolin and Levistilide A).And literature mining confirmed the vasospasmolytic activity and neuroprotective effect activity of TTNC.CONCLUSIONS Integrating single-cell data and network disturbance tools provides a new strategy for the MoA of multi-components drug through cell subtyping.