PMID- 31497913
OWN - NLM
STAT- MEDLINE
DCOM- 20200327
LR  - 20200327
IS  - 1099-1573 (Electronic)
IS  - 0951-418X (Linking)
VI  - 34
IP  - 1
DP  - 2020 Jan
TI  - Quercetin protects against cisplatin-induced acute kidney injury by inhibiting 
      Mincle/Syk/NF-kappaB signaling maintained macrophage inflammation.
PG  - 139-152
LID - 10.1002/ptr.6507 [doi]
AB  - Acute kidney injury (AKI) with high incidence and mortality is the main cause of 
      chronic kidney disease. Previous studies have indicated that quercetin, an 
      abundant flavonoid in plants, exhibited renoprotective role in AKI. However, the 
      underlying mechanism is largely unknown. In this study, we try to explore whether 
      quercetin protects against AKI by inhibiting macrophage inflammation via 
      regulation of Mincle/Syk/NF-kappaB signaling. The results demonstrated that quercetin 
      can significantly inhibit expression and secretion of IL-1beta, IL-6, and TNF-alpha in 
      LPS-induced bone marrow-derived macrophages (BMDMs) and reduce activity of 
      Mincle/Syk/NF-kappaB signaling in vitro. We also found that quercetin can strongly 
      reduce the concentration of serum creatinine, BUN, IL-1beta, IL-6, and TNF-alpha in 
      cisplatin-induced AKI model. Furthermore, quercetin down-regulated protein levels 
      of Mincle, phosphorylated Syk and NF-kappaB in kidney macrophages of AKI, as well as 
      inhibited M1, up-regulated M2 macrophage activity. Notably, the down-regulation 
      of LPS-induced inflammation by quercetin was reversed after adding TDB (an 
      agonist of Mincle) in BMDMs, suggesting that quercetin suppresses macrophage 
      inflammation may mainly through inhibiting Mincle and its downstream signaling. 
      In summary, these findings clarified a new mechanism of quercetin improving 
      AKI-induced kidney inflammation and injury, which provides a new drug option for 
      the clinical treatment of AKI.
CI  - (c) 2019 John Wiley & Sons, Ltd.
FAU - Tan, Rui-Zhi
AU  - Tan RZ
AD  - Research Center of Combine Traditional Chinese and Western Medicine, Affiliated 
      Traditional Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 
      China.
FAU - Wang, Chen
AU  - Wang C
AD  - Research Center of Combine Traditional Chinese and Western Medicine, Affiliated 
      Traditional Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 
      China.
FAU - Deng, Chong
AU  - Deng C
AD  - Clinical Laboratory, Affiliated Traditional Medicine Hospital, Southwest Medical 
      University, Luzhou, Sichuan, China.
FAU - Zhong, Xia
AU  - Zhong X
AD  - Research Center of Combine Traditional Chinese and Western Medicine, Affiliated 
      Traditional Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 
      China.
FAU - Yan, Ying
AU  - Yan Y
AD  - Research Center of Combine Traditional Chinese and Western Medicine, Affiliated 
      Traditional Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 
      China.
FAU - Luo, Yi
AU  - Luo Y
AD  - School of Integrated Traditional Chinese and Western Medicine, Southwest Medical 
      University, Luzhou, Sichuan, China.
FAU - Lan, Hui-Yao
AU  - Lan HY
AD  - Li Ka Shing Institute of Health Sciences, and Department of Medicine and 
      Therapeutics, and Shenzhen Research Institute, The Chinese University of Hong 
      Kong, Hong Kong, China.
FAU - He, Tao
AU  - He T
AD  - School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, 
      China.
FAU - Wang, Li
AU  - Wang L
AUID- ORCID: 0000-0003-3881-3149
AD  - Research Center of Combine Traditional Chinese and Western Medicine, Affiliated 
      Traditional Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 
      China.
LA  - eng
GR  - 2017LZXNYD-P01/Luzhou - Southwest Medical University Joint Project/
GR  - 2018LZXNYD-PT03/Luzhou - Southwest Medical University Joint Project/
GR  - Luzhou Municipal - Southwest Medical University Joint Special Grant for the 
      Introduction of High-level Talents/
GR  - S201910799168/Students Innovation Training Program of Sichuan Province/
GR  - 2018-ZRQN-165/Youth Funding Program of Southwest Medical University/
PT  - Journal Article
DEP - 20190909
PL  - England
TA  - Phytother Res
JT  - Phytotherapy research : PTR
JID - 8904486
RN  - 0 (Antioxidants)
RN  - 9IKM0I5T1E (Quercetin)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Acute Kidney Injury/*chemically induced/*drug therapy
MH  - Animals
MH  - Antioxidants/pharmacology/*therapeutic use
MH  - Cisplatin/*adverse effects
MH  - Disease Models, Animal
MH  - Humans
MH  - Inflammation/*drug therapy
MH  - Male
MH  - Mice
MH  - Quercetin/pharmacology
OTO - NOTNLM
OT  - AKI
OT  - Mincle
OT  - inflammation
OT  - macrophage
OT  - quercetin
EDAT- 2019/09/10 06:00
MHDA- 2020/03/28 06:00
CRDT- 2019/09/10 06:00
PHST- 2019/07/08 00:00 [received]
PHST- 2019/08/19 00:00 [revised]
PHST- 2019/08/21 00:00 [accepted]
PHST- 2019/09/10 06:00 [pubmed]
PHST- 2020/03/28 06:00 [medline]
PHST- 2019/09/10 06:00 [entrez]
AID - 10.1002/ptr.6507 [doi]
PST - ppublish
SO  - Phytother Res. 2020 Jan;34(1):139-152. doi: 10.1002/ptr.6507. Epub 2019 Sep 9.