PMID- 38203454
OWN - NLM
STAT- MEDLINE
DCOM- 20240112
LR  - 20240116
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 25
IP  - 1
DP  - 2023 Dec 24
TI  - Protective Effects of Sophoraflavanone G by Inhibiting TNF-alpha-Induced 
      MMP-9-Mediated Events in Brain Microvascular Endothelial Cells.
LID - 10.3390/ijms25010283 [doi]
LID - 283
AB  - The regulation of matrix metalloproteinases (MMPs), especially MMP-9, has a 
      critical role in both physiological and pathological events in the central 
      nervous system (CNS). MMP-9 is an indicator of inflammation that triggers several 
      CNS disorders, including neurodegeneration. Tumor necrosis factor-alpha (TNF-alpha) has 
      the ability to stimulate the production of different inflammatory factors, 
      including MMP-9, in several conditions. Numerous phytochemicals are hypothesized 
      to mitigate inflammation, including the CNS. Among them, a flavonoid compound, 
      sophoraflavanone G (SG), found in Sophora flavescens has been found to possess 
      several medicinal properties, including anti-bacterial and anti-inflammatory 
      effects. In this study, mouse brain microvascular endothelial cells (bMECs) were 
      used to explore TNF-alpha-induced MMP-9 signaling. The effects of SG on TNF-alpha-induced 
      MMP-9 expression and its mechanisms were further evaluated. Our study revealed 
      that the expression of MMP-9 in bMECs was stimulated by TNF-alpha through the 
      activation of ERK1/2, p38 MAPK, and JNK1/2 via the TNF receptor (TNFR) with a 
      connection to the NF-kappaB signaling pathway. Moreover, we found that SG can 
      interact with the TNFR. The upregulation of MMP-9 by TNF-alpha may lead to the 
      disruption of zonula occludens-1 (ZO-1), which can be mitigated by SG 
      administration. These findings provide evidence that SG may possess 
      neuroprotective properties by inhibiting the signaling pathways associated with 
      TNFR-mediated MMP-9 expression and the subsequent disruption of tight junctions 
      in brain microvascular endothelial cells.
FAU - Lee, Tsong-Hai
AU  - Lee TH
AUID- ORCID: 0000-0002-3935-5963
AD  - Stroke Center and Stroke Section, Department of Neurology, Chang Gung Memorial 
      Hospital, and College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
FAU - Chen, Jiun-Liang
AU  - Chen JL
AD  - Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, 
      Chang Gung Memorial Hospital, and School of Traditional Chinese Medicine, College 
      of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
FAU - Tsai, Ming-Ming
AU  - Tsai MM
AUID- ORCID: 0000-0002-4495-6616
AD  - Division of Basic Medical Sciences, Department of Nursing, Research Center for 
      Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, 
      Chang Gung University of Science and Technology, Taoyuan 333, Taiwan.
AD  - Department of General Surgery, New Taipei Municipal Tucheng Hospital, New Taipei 
      236, Taiwan.
FAU - Wu, Yi-Hsuan
AU  - Wu YH
AD  - Division of Basic Medical Sciences, Department of Nursing, Research Center for 
      Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, 
      Chang Gung University of Science and Technology, Taoyuan 333, Taiwan.
FAU - Tseng, Hui-Ching
AU  - Tseng HC
AD  - Division of Basic Medical Sciences, Department of Nursing, Research Center for 
      Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, 
      Chang Gung University of Science and Technology, Taoyuan 333, Taiwan.
FAU - Cheng, Li-Ching
AU  - Cheng LC
AUID- ORCID: 0000-0003-3214-7798
AD  - Division of Basic Medical Sciences, Department of Nursing, Research Center for 
      Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, 
      Chang Gung University of Science and Technology, Taoyuan 333, Taiwan.
AD  - Department of General Surgery, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
FAU - Shanmugam, Velayuthaprabhu
AU  - Shanmugam V
AUID- ORCID: 0000-0003-3700-1907
AD  - Department of Biotechnology, Bharathiar University, Coimbatore 641046, India.
FAU - Hsieh, Hsi-Lung
AU  - Hsieh HL
AUID- ORCID: 0000-0001-8302-2472
AD  - Division of Basic Medical Sciences, Department of Nursing, Research Center for 
      Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, 
      Chang Gung University of Science and Technology, Taoyuan 333, Taiwan.
AD  - Department of Neurology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
LA  - eng
GR  - MOST111-2320-B-255-004-MY3, MOST110-2635-B-255-001/Ministry of Science and 
      Technology, Taiwan/
GR  - CMRPF1M0071~2, CMRPF1M0111~2, CMRPF1L0081, CMRPF1N0011/Chang Gung Medical 
      Research Foundation/
GR  - ZRRPF3M0091/Chang Gung University of Science and Technology/
PT  - Journal Article
DEP - 20231224
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 97938-30-2 (vexibinol)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - 0 (Flavanones)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Endothelial Cells
MH  - *Tumor Necrosis Factor-alpha/pharmacology
MH  - Matrix Metalloproteinase 9
MH  - Brain
MH  - Inflammation
MH  - *Flavanones
PMC - PMC10779338
OTO - NOTNLM
OT  - brain microvascular endothelial cells
OT  - brain protection
OT  - matrix metalloproteinase-9
OT  - sophoraflavanone G
OT  - zonula occludens-1
COIS- The authors declare no conflicts of interest.
EDAT- 2024/01/11 07:43
MHDA- 2024/01/12 06:42
PMCR- 2023/12/24
CRDT- 2024/01/11 01:18
PHST- 2023/12/02 00:00 [received]
PHST- 2023/12/22 00:00 [revised]
PHST- 2023/12/23 00:00 [accepted]
PHST- 2024/01/12 06:42 [medline]
PHST- 2024/01/11 07:43 [pubmed]
PHST- 2024/01/11 01:18 [entrez]
PHST- 2023/12/24 00:00 [pmc-release]
AID - ijms25010283 [pii]
AID - ijms-25-00283 [pii]
AID - 10.3390/ijms25010283 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Dec 24;25(1):283. doi: 10.3390/ijms25010283.