PMID- 32661350
OWN - NLM
STAT- MEDLINE
DCOM- 20210628
LR  - 20210628
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 41
IP  - 10
DP  - 2020 Oct
TI  - Fisetin alleviates sepsis-induced multiple organ dysfunction in mice via 
      inhibiting p38 MAPK/MK2 signaling.
PG  - 1348-1356
LID - 10.1038/s41401-020-0462-y [doi]
AB  - Sepsis-induced multiple organ dysfunction and inflammatory response are 
      life-threatening symptoms without effective treatment. Fisetin, a dietary 
      flavonoid extracted from berries and family Fabaceae, has displayed 
      neuroprotective and anti-oxidant activities. In this study we investigated 
      whether fisetin exerted a protective effect against sepsis-induced multiple organ 
      dysfunction in mouse cecum ligation and puncture (CLP) model. The mice were 
      injected with fisetin (10 mg/kg, ip) 0.5 h prior to CLP, and sacrificed 18 h 
      after CLP. We found that fisetin administration significantly alleviated 
      CLP-induced lung, liver and kidney injury, as well as the expression levels of 
      interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and IL-1beta in bronchoalveolar 
      lavage fluid (BALF). In lipopolysaccharide (LPS)-treated mouse bone 
      marrow-derived macrophages (BMDMs), application of fisetin (3-10 muM) 
      dose-dependently inhibited the expression levels of IL-6, TNF-alpha, IL-1beta, and 
      inducible nitric oxide synthase (iNOS). Furthermore, fisetin dose-dependently 
      inhibited the phosphorylation of p38 MAPK, MK2, and transforming growth 
      factor-beta-activated kinase (TAK) 1 via attenuating the interaction between TAK1 
      and TAK-binding proteins (TAB) 1. These results demonstrate that fisetin is a 
      promising agent for protecting against sepsis-induced inflammatory response and 
      organ injury via inhibiting macrophage activation.
FAU - Zhang, Hai-Feng
AU  - Zhang HF
AD  - Department of Nephrology, First Affiliated Hospital of Bengbu Medical College, 
      Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical 
      College, Bengbu, 233004, China.
FAU - Zhang, Hai-Bo
AU  - Zhang HB
AD  - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of 
      Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, 
      China.
FAU - Wu, Xue-Ping
AU  - Wu XP
AD  - Department of Nephrology, First Affiliated Hospital of Bengbu Medical College, 
      Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical 
      College, Bengbu, 233004, China.
FAU - Guo, Ya-Ling
AU  - Guo YL
AD  - Department of Nephrology, First Affiliated Hospital of Bengbu Medical College, 
      Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical 
      College, Bengbu, 233004, China.
FAU - Cheng, Wei-Dong
AU  - Cheng WD
AD  - Department of Nephrology, First Affiliated Hospital of Bengbu Medical College, 
      Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical 
      College, Bengbu, 233004, China.
FAU - Qian, Feng
AU  - Qian F
AD  - Department of Nephrology, First Affiliated Hospital of Bengbu Medical College, 
      Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical 
      College, Bengbu, 233004, China. fengqian@sjtu.edu.cn.
AD  - Engineering Research Center of Cell & Therapeutic Antibody, Ministry of 
      Education, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, 
      China. fengqian@sjtu.edu.cn.
AD  - Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer 
      Institute, Xuzhou Medical University, Xuzhou, 221004, China. 
      fengqian@sjtu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20200713
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Cytokines)
RN  - 0 (Flavonols)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Protective Agents)
RN  - 147257-52-1 (Nfkb1 protein, mouse)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - OO2ABO9578 (fisetin)
SB  - IM
MH  - Animals
MH  - Cecum/surgery
MH  - Cytokines/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Flavonols/*therapeutic use
MH  - Kidney/pathology
MH  - Liver/pathology
MH  - Lung/pathology
MH  - MAP Kinase Signaling System/*drug effects
MH  - Macrophage Activation/drug effects
MH  - Macrophages/drug effects
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Multiple Organ Failure/epidemiology/pathology/*prevention & control
MH  - NF-kappa B p50 Subunit/metabolism
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Protective Agents/*therapeutic use
MH  - Sepsis/complications
PMC - PMC7608145
OTO - NOTNLM
OT  - Fisetin
OT  - inflammation
OT  - macrophages
OT  - mouse cecum ligation and puncture (CLP) model
OT  - multiple organ dysfunction
OT  - sepsis
COIS- The authors declare no competing interests.
EDAT- 2020/07/15 06:00
MHDA- 2021/06/29 06:00
PMCR- 2021/10/01
CRDT- 2020/07/15 06:00
PHST- 2020/03/24 00:00 [received]
PHST- 2020/06/11 00:00 [accepted]
PHST- 2020/07/15 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2020/07/15 06:00 [entrez]
PHST- 2021/10/01 00:00 [pmc-release]
AID - 10.1038/s41401-020-0462-y [pii]
AID - 462 [pii]
AID - 10.1038/s41401-020-0462-y [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2020 Oct;41(10):1348-1356. doi: 10.1038/s41401-020-0462-y. 
      Epub 2020 Jul 13.