PMID- 32161541
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220413
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 11
DP  - 2020
TI  - Divergence and Convergence of Cerebral Ischemia Pathways Profile Deciphers 
      Differential Pure Additive and Synergistic Mechanisms.
PG  - 80
LID - 10.3389/fphar.2020.00080 [doi]
LID - 80
AB  - AIM: The variable mechanisms on additive and synergistic effects of jasminoidin 
      (JA)-Baicalin (BA) combination and JA-ursodeoxycholic acid (UA) combination in 
      treating cerebral ischemia are not completely understood. In this study, we 
      explored the differential pure mechanisms of additive and synergistic effects 
      based on pathway analysis that excluded ineffective interference. METHODS: The 
      MCAO mice were divided into eight groups: sham, vehicle, BA, JA, UA, Concha 
      Margaritifera (CM), BA-JA combination (BJ), and JA-UA combination (JU). The 
      additive and synergistic effects of combination groups were identified by 
      cerebral infarct volume calculation. The differentially expressed genes based on 
      a microarray chip containing 16,463 oligoclones were uploaded to GeneGo MetaCore 
      software for pathway analyses and function catalogue. The comparison of specific 
      pathways and functions crosstalk between different groups were analyzed to reveal 
      the underlying additive and synergistic pharmacological variations. RESULTS: 
      Additive BJ and synergistic JU were more effective than monotherapies of BA, JA, 
      and UA, while CM was ineffective. Compared with monotherapies, 43 pathways and 
      six functions were found uniquely in BJ group, with 33 pathways and three 
      functions in JU group. We found six overlapping pathways and six overlapping 
      functions between BJ and JU groups, which mainly involved central nervous system 
      development. Thirty-seven specific pathways and 10 functions were activated by 
      additive BJ, which were mainly related to cell adhesion and G-protein signaling; 
      and 27 specific pathways and three functions of synergistic JU were associated 
      with regulation of metabolism, DNA damage, and translation. The overlapping and 
      distinct pathways and functions may contribute to different additive and 
      synergistic effects. CONCLUSION: The divergence pathways of pure additive effect 
      of BJ were mainly related to cell adhesion and G-protein signaling, while the 
      pure synergistic mechanism of JU depended on metabolism, translation and DNA 
      damage. Such a systematic analysis of pathways may provide an important paradigm 
      to reveal the pharmacological mechanisms underlying drug combinations.
CI  - Copyright (c) 2020 Wei, Wang, Li, Gu, Liu and Wang.
FAU - Wei, Penglu
AU  - Wei P
AD  - Institute of Basic Research in Clinical Medicine, China Academy of Chinese 
      Medical Sciences, Beijing, China.
FAU - Wang, Pengqian
AU  - Wang P
AD  - Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 
      Beijing, China.
FAU - Li, Bing
AU  - Li B
AD  - Institute of Information on Traditional Chinese Medicine, China Academy of 
      Chinese Medical Sciences, Beijing, China.
FAU - Gu, Hao
AU  - Gu H
AD  - Institute of Basic Research in Clinical Medicine, China Academy of Chinese 
      Medical Sciences, Beijing, China.
FAU - Liu, Jun
AU  - Liu J
AD  - Institute of Basic Research in Clinical Medicine, China Academy of Chinese 
      Medical Sciences, Beijing, China.
FAU - Wang, Zhong
AU  - Wang Z
AD  - Institute of Basic Research in Clinical Medicine, China Academy of Chinese 
      Medical Sciences, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20200225
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC7053362
OTO - NOTNLM
OT  - additive effect
OT  - cerebral ischemia
OT  - pure mechanism
OT  - signaling pathway
OT  - synergistic effect
EDAT- 2020/03/13 06:00
MHDA- 2020/03/13 06:01
PMCR- 2020/02/25
CRDT- 2020/03/13 06:00
PHST- 2019/10/17 00:00 [received]
PHST- 2020/01/27 00:00 [accepted]
PHST- 2020/03/13 06:00 [entrez]
PHST- 2020/03/13 06:00 [pubmed]
PHST- 2020/03/13 06:01 [medline]
PHST- 2020/02/25 00:00 [pmc-release]
AID - 10.3389/fphar.2020.00080 [doi]
PST - epublish
SO  - Front Pharmacol. 2020 Feb 25;11:80. doi: 10.3389/fphar.2020.00080. eCollection 
      2020.