PMID- 33192512
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220418
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 11
DP  - 2020
TI  - The Mechanism of Aureusidin in Suppressing Inflammatory Response in Acute Liver 
      Injury by Regulating MD2.
PG  - 570776
LID - 10.3389/fphar.2020.570776 [doi]
LID - 570776
AB  - OBJECTIVE: In this study, we mainly explored the mechanism and target of the 
      anti-inflammatory effects of Aureusidin (Aur) in acute liver injury. METHODS: 
      Lipopolysaccharide (LPS) was used to induce inflammatory injury in Kupffer cells 
      (KCs) in vitro. After Aur treatment with gradient concentration, flow cytometry, 
      propidium iodide (PI) staining, and Hoechst 33342 staining were used to detect 
      the apoptotic level of KCs, and an enzyme-linked immunosorbent assay (ELISA) was 
      used to detect the expression levels of inflammatory factors, including 
      Interleukin-1beta (IL-1beta), Interleukin-18 (IL-18), and tumor necrosis factor alpha 
      (TNF-alpha). Western blot was used to detect the expression of toll-like receptor 4 
      (TLR4), myeloid differentiation protein-2 (MD2), MyD88, and p-P65. Aur was 
      labeled with biotin, followed by a pull-down assay to detect its binding with 
      MD2. Moreover, D-GalN/LPS was used to induce acute liver injury in mice in vitro, 
      followed by Aur treatment by gavage. H&E staining was used to detect the 
      pathological changes of liver tissue, an IF assay was used to detect the 
      expression of MD2, Western blot was used to detect the expression of relevant 
      proteins. RESULTS: Aur pretreatment could significantly inhibit LPS-induced KC 
      injury, downregulate the apoptotic level, inhibit the expression of inflammatory 
      factors, decrease the level of MDA, and downregulate the expression of MD2 in 
      cells. Aur could inhibit the activation level of TLR4/MD2-NF-kappaB in a 
      dose-dependent pattern, a high dose of Aur had a superior effect compared to 
      low-dose Aur. In the case of MD2 deletion, the effects of Aur were suppressed. 
      Additionally, pull-down and co-immunoprecipitation assays show that Aur can bind 
      with the MD2 protein to inhibit the activation of TLR4/MD2-NF-kappaB. Results of mice 
      experiments also showed that Aur could relieve liver injury, decrease the levels 
      of ALT and AST, and simultaneously downregulate the levels of inflammatory 
      factors in tissues and peripheral blood. CONCLUSION: We found that Aur exerted an 
      anti-inflammatory effect by directly targeting the MD2 protein, further 
      inhibiting the expression of TLR4/MD2-NF-kappaB, thereby relieving acute liver 
      injury. Therefore, Aur might be a potential inhibitor for MD2.
CI  - Copyright (c) 2020 Yang, Han, Sheng, Wang, Zhou, Li, Guo and Ruan.
FAU - Yang, Yi
AU  - Yang Y
AD  - Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, 
      Jiaxing, China.
FAU - Han, Chenyang
AU  - Han C
AD  - Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, 
      Jiaxing, China.
FAU - Sheng, Yongjia
AU  - Sheng Y
AD  - Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, 
      Jiaxing, China.
FAU - Wang, Jin
AU  - Wang J
AD  - Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, 
      Jiaxing, China.
FAU - Zhou, Xiaohong
AU  - Zhou X
AD  - Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, 
      Jiaxing, China.
FAU - Li, Wenyan
AU  - Li W
AD  - Department of Pharmacy, The Second Affiliated Hospital of Jiaxing University, 
      Jiaxing, China.
FAU - Guo, Li
AU  - Guo L
AD  - Department of Center Laboratory, The Second Affiliated Hospital of Jiaxing 
      University, Jiaxing, China.
FAU - Ruan, Shuiliang
AU  - Ruan S
AD  - Department of Center Laboratory, The Second Affiliated Hospital of Jiaxing 
      University, Jiaxing, China.
LA  - eng
PT  - Journal Article
DEP - 20201028
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
EIN - Front Pharmacol. 2021 Dec 06;12:802304. PMID: 34938199
PMC - PMC7655772
OTO - NOTNLM
OT  - acute liver injury
OT  - aureusidinmyeloid
OT  - differentiation protein 2
OT  - inflammatory response
OT  - lipopolysaccharide
OT  - toll likes receptor
EDAT- 2020/11/17 06:00
MHDA- 2020/11/17 06:01
PMCR- 2020/10/28
CRDT- 2020/11/16 08:44
PHST- 2020/06/09 00:00 [received]
PHST- 2020/08/28 00:00 [accepted]
PHST- 2020/11/16 08:44 [entrez]
PHST- 2020/11/17 06:00 [pubmed]
PHST- 2020/11/17 06:01 [medline]
PHST- 2020/10/28 00:00 [pmc-release]
AID - 10.3389/fphar.2020.570776 [doi]
PST - epublish
SO  - Front Pharmacol. 2020 Oct 28;11:570776. doi: 10.3389/fphar.2020.570776. 
      eCollection 2020.