PMID- 37838292
OWN - NLM
STAT- MEDLINE
DCOM- 20231121
LR  - 20240221
IS  - 1872-7573 (Electronic)
IS  - 0378-8741 (Linking)
VI  - 319
IP  - Pt 3
DP  - 2024 Jan 30
TI  - Integration of single-nucleus RNA sequencing and network disturbance to elucidate 
      crosstalk between multicomponent drugs and trigeminal ganglia cells in migraine.
PG  - 117286
LID - S0378-8741(23)01156-X [pii]
LID - 10.1016/j.jep.2023.117286 [doi]
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Migraine is caused by hyperactivity of the 
      trigeminovascular system, where trigeminal ganglia (TG) plays an important role. 
      TG is composed of multiple neuronal and non-neuronal cell types, which is related 
      to "neuro-inflammation-vascular" disorder in migraine. Tou Tong Ning capsule 
      (TTNC), a CFDA-approved traditional Chinese medicine for treating migraine, has 
      the characteristics of "multicomponents, multitargets, multipathways". AIM OF THE 
      STUDY: To clarify the mechanism of TTNC and elucidate crosstalk between 
      multicomponent drugs and neuronal and non-neuronal functions and cells in 
      migraine. MATERIALS AND METHODS: We integrated single-nucleus RNA sequencing and 
      a quantitative evaluation algorithm of the disturbance of multitarget drugs on 
      the disease network and explored the specific pathology of migraine and 
      corresponding compounds. A cerebrovascular smooth muscle spasmolytic activity 
      experiment was carried out to verify the results of the bioinformatics analysis. 
      RESULTS: TTNC exhibited its regulation activities in neuronal and non-neuronal 
      aspects based on drugs attack to four subnetworks and cell specific networks, 
      which explored the MoA of TTNC in comprehensive and refined perspectives. 
      Compared to neuronal regulation, TTNC showed more significant attack score on 
      non-neuronal biological function (smooth muscle and vessel). And TTNC compound 
      clusters C1, C6 and C7, targeting non-neuronal function and cells, had larger 
      group area than C10, C4 and C6 for neuronal function and cell, which implied that 
      TTNC may mainly regulate the non-neuronal function, e.g., vessel smooth muscle 
      contraction. Contraction of cerebrovascular smooth muscle of mice ex vivo 
      confirmed the vasodilation activity of TTNC and active compounds from C1, C6, C9 
      (Emodin, Luteolin and Levistilide A). Literature mining confirmed the 
      vasospasmodolytic activity and neuroprotective effect of TTNC. CONCLUSIONS: The 
      study found that TTNC may primarily alleviate non-neuronal functional disorders 
      in migraine by relaxing cerebral vascular smooth muscle cell spasm to alleviate 
      migraine. Integrating single-nucleus RNA sequencing data and network disturbance 
      tools provides a new strategy for the pharmacological mechanism of multicomponent 
      drugs through cell subtyping.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Zhang, Bo
AU  - Zhang B
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China.
FAU - Xi, Yujie
AU  - Xi Y
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China; Beijing Key Laboratory of Traditional Chinese Medicine Basic 
      Research on Prevention and Treatment for Major Diseases, Experimental Research 
      Center, China Academy of Chinese Medical Sciences, Beijing, China.
FAU - Huang, Ying
AU  - Huang Y
AD  - Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on 
      Prevention and Treatment for Major Diseases, Experimental Research Center, China 
      Academy of Chinese Medical Sciences, Beijing, China.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China.
FAU - Guo, Feifei
AU  - Guo F
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China. Electronic address: ffguo@icmm.ac.cn.
FAU - Yang, Hongjun
AU  - Yang H
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China; Beijing Key Laboratory of Traditional Chinese Medicine Basic 
      Research on Prevention and Treatment for Major Diseases, Experimental Research 
      Center, China Academy of Chinese Medical Sciences, Beijing, China; China Academy 
      of Chinese Medical Sciences, Beijing, China. Electronic address: 
      hjyang@icmm.ac.cn.
LA  - eng
PT  - Journal Article
DEP - 20231013
PL  - Ireland
TA  - J Ethnopharmacol
JT  - Journal of ethnopharmacology
JID - 7903310
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Trigeminal Ganglion
MH  - Cell Physiological Phenomena
MH  - *Migraine Disorders/drug therapy/genetics
MH  - Muscle, Smooth, Vascular
MH  - Sequence Analysis, RNA
OTO - NOTNLM
OT  - Multi-components
OT  - Network disturbance
OT  - Polypharmacology
OT  - Single-nucleus RNA sequencing
OT  - Tou Tong Ning capsule
OT  - Vascular
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/10/15 05:46
MHDA- 2023/11/21 06:42
CRDT- 2023/10/14 19:29
PHST- 2023/08/02 00:00 [received]
PHST- 2023/10/02 00:00 [revised]
PHST- 2023/10/04 00:00 [accepted]
PHST- 2023/11/21 06:42 [medline]
PHST- 2023/10/15 05:46 [pubmed]
PHST- 2023/10/14 19:29 [entrez]
AID - S0378-8741(23)01156-X [pii]
AID - 10.1016/j.jep.2023.117286 [doi]
PST - ppublish
SO  - J Ethnopharmacol. 2024 Jan 30;319(Pt 3):117286. doi: 10.1016/j.jep.2023.117286. 
      Epub 2023 Oct 13.