PMID- 35987258
OWN - NLM
STAT- MEDLINE
DCOM- 20220907
LR  - 20220907
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 931
DP  - 2022 Sep 15
TI  - Integrating network pharmacology, transcriptomics, and molecular simulation to 
      reveal the mechanism of tert-butylhydroquinone for treating diabetic retinopathy.
PG  - 175215
LID - S0014-2999(22)00476-9 [pii]
LID - 10.1016/j.ejphar.2022.175215 [doi]
AB  - Diabetic retinopathy (DR), a common microvascular complication of diabetes 
      mellitus, is a significant cause of blindness. As one of the crucial factors in 
      the pathogenesis of DR, oxidative stress provides new insights for the treatment 
      of DR. Tert-butylhydroquinone (TBHQ), an efficient phenolic antioxidant, has been 
      proved to inhibit diabetic retina injury. However, the mechanism of TBHQ for DR 
      treatment is still unclear. The present study was designed to investigate the 
      potential mechanism of TBHQ for treating DR. Firstly, the potential targets of 
      TBHQ and DR were selected to construct protein-protein interaction network, which 
      was applied to illustrate the potential mechanism of TBHQ against DR. Combined 
      with transcriptomics and molecular simulation, the potential mechanisms were 
      systematically verified. The results showed that TBHQ inhibited retinal 
      microvascular injury by regulating oxidative stress, inflammation, cell 
      proliferation-death regulation, and vascular system development. The mechanisms 
      of these activities were associated with hypoxia-inducible factor-1 (HIF-1), 
      nuclear factor-erythroid 2 related factor 2 (Nrf2), vascular endothelial growth 
      factor (VEGF), forkhead box O (FoxO), phosphatidylinositol 3-kinase 
      (PI3K)/protein kinase B (AKT), and rhoptry-associated protein1 (Rap1) signaling 
      pathways and their related targets nitric oxide synthase 3 (NOS3), 
      mitogen-activated protein kinase 8 (MAPK8), prostaglandin-endoperoxide synthase 2 
      (PTGS2), and heme oxygenase 1 (HMOX1). In conclusion, a systematic perspective 
      for the mechanism of TBHQ against DR was revealed by present study which lays a 
      foundation for the application of TBHQ in treating DR.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Liu, Chaoqun
AU  - Liu C
AD  - Key Laboratory of TCM-information Engineer of State Administration of TCM, School 
      of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 
      102488, China.
FAU - Ren, Yue
AU  - Ren Y
AD  - Key Laboratory of TCM-information Engineer of State Administration of TCM, School 
      of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 
      102488, China.
FAU - Sui, Xin
AU  - Sui X
AD  - Information and Educational Technology Center, Beijing University of Chinese 
      Medicine, Beijing, 102488, China.
FAU - Liu, Kaiyang
AU  - Liu K
AD  - Key Laboratory of TCM-information Engineer of State Administration of TCM, School 
      of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 
      102488, China.
FAU - Zhang, Jianing
AU  - Zhang J
AD  - Key Laboratory of TCM-information Engineer of State Administration of TCM, School 
      of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 
      102488, China.
FAU - Wang, Zian
AU  - Wang Z
AD  - Key Laboratory of TCM-information Engineer of State Administration of TCM, School 
      of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 
      102488, China.
FAU - Li, Yingying
AU  - Li Y
AD  - Key Laboratory of TCM-information Engineer of State Administration of TCM, School 
      of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 
      102488, China.
FAU - Zhang, Yanling
AU  - Zhang Y
AD  - Key Laboratory of TCM-information Engineer of State Administration of TCM, School 
      of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 
      102488, China. Electronic address: zhangyanling@bucm.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20220818
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Antioxidants)
RN  - 0 (Hydroquinones)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - C12674942B (2-tert-butylhydroquinone)
SB  - IM
MH  - Antioxidants/metabolism/pharmacology/therapeutic use
MH  - *Diabetes Mellitus
MH  - *Diabetic Retinopathy/drug therapy
MH  - Humans
MH  - Hydroquinones
MH  - NF-E2-Related Factor 2/metabolism
MH  - Network Pharmacology
MH  - Oxidative Stress
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Transcriptome
MH  - Vascular Endothelial Growth Factor A/metabolism
OTO - NOTNLM
OT  - Diabetic retinopathy
OT  - Molecular mechanism
OT  - Molecular simulation
OT  - Network pharmacology
OT  - Tert-butylhydroquinone
OT  - Transcriptomics
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- 2022/08/21 06:00
MHDA- 2022/09/08 06:00
CRDT- 2022/08/20 19:23
PHST- 2022/04/20 00:00 [received]
PHST- 2022/08/05 00:00 [revised]
PHST- 2022/08/12 00:00 [accepted]
PHST- 2022/08/21 06:00 [pubmed]
PHST- 2022/09/08 06:00 [medline]
PHST- 2022/08/20 19:23 [entrez]
AID - S0014-2999(22)00476-9 [pii]
AID - 10.1016/j.ejphar.2022.175215 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2022 Sep 15;931:175215. doi: 10.1016/j.ejphar.2022.175215. Epub 
      2022 Aug 18.