PMID- 34987391
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220107
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Methyl Gallate Improves Hyperuricemia Nephropathy Mice Through Inhibiting NLRP3 
      Pathway.
PG  - 759040
LID - 10.3389/fphar.2021.759040 [doi]
LID - 759040
AB  - Hyperuricemia nephropathy (HN) is a form of chronic tubulointerstitial 
      inflammation, caused by the deposition of monosodium urate crystals (MSU) in the 
      distal collecting duct and medullary interstitium, associated with a secondary 
      inflammatory reaction. Numerous published reports indicated that NLRP3 
      inflammasome pathway play crucial roles in HN symptoms. The present study aims to 
      investigate the protective effects of methyl gallate on HN mice and the 
      underlying mechanisms. An HN model was established by intraperitoneal injection 
      of potassium oxide (PO) to assess the effect of methyl gallate on renal 
      histopathological changes, renal function, cytokine levels and expressions of 
      NLRP3-related protein in HN mice. Moreover, in vitro models of lipopolysaccharide 
      (LPS)-stimulated bone marrow-derived macrophages (BMDMs) and human peripheral 
      blood mononuclear cells (PBMCs) were established to explore the mechanism of 
      methyl gallate on NLRP3 inflammasome activation. The results showed that methyl 
      gallate significantly ameliorated HN by inhibiting uric acid production and 
      promoting uric acid excretion as well as ameliorating renal injury induced by 
      NLRP3 activation. Mechanistically, methyl gallate is a direct NLRP3 inhibitor 
      that inhibits NLRP3 inflammasome activation but has no effect on the activation 
      of AIM2 or NLRC4 inflammasomes in macrophages. Furthermore, methyl gallate 
      inhibited the assembly of NLRP3 inflammasomes by blocking the ROS over-generation 
      and oligomerization of NLRP3. Methyl gallate was also active ex vivo against 
      ATP-treated PBMCs and synovial fluid mononuclear cells from patients with gout. 
      In conclusion, methyl gallate has a nephroprotective effect against PO-induced HN 
      through blocking the oligomerization of NLRP3 and then exerting anti-inflammatory 
      activity in the NLRP3-driven diseases.
CI  - Copyright (c) 2021 Liu, Wang, Li, Hu, Xu, Wu, Bai, Ping, Lan and Chen.
FAU - Liu, Peng
AU  - Liu P
AD  - School of Pharmaceutical Sciences, South-Central University for Nationalities, 
      Wuhan, China.
FAU - Wang, Wen
AU  - Wang W
AD  - School of Pharmaceutical Sciences, South-Central University for Nationalities, 
      Wuhan, China.
FAU - Li, Qiang
AU  - Li Q
AD  - School of Pharmaceutical Sciences, South-Central University for Nationalities, 
      Wuhan, China.
FAU - Hu, Xin
AU  - Hu X
AD  - School of Pharmaceutical Sciences, South-Central University for Nationalities, 
      Wuhan, China.
FAU - Xu, Bingyong
AU  - Xu B
AD  - Zhejiang Heze Pharmaceutical Technology Co., Ltd., Hangzhou, China.
FAU - Wu, Chen
AU  - Wu C
AD  - School of Pharmaceutical Sciences, South-Central University for Nationalities, 
      Wuhan, China.
FAU - Bai, Lijie
AU  - Bai L
AD  - School of Pharmaceutical Sciences, South-Central University for Nationalities, 
      Wuhan, China.
FAU - Ping, Li
AU  - Ping L
AD  - Center for Drug Safety Evaluation and Research, College of Pharmaceutical 
      Sciences, Zhejiang University, Hangzhou, China.
FAU - Lan, Zhou
AU  - Lan Z
AD  - School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.
FAU - Chen, Lvyi
AU  - Chen L
AD  - School of Pharmaceutical Sciences, South-Central University for Nationalities, 
      Wuhan, China.
LA  - eng
PT  - Journal Article
DEP - 20211220
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8721208
OTO - NOTNLM
OT  - NLRP3
OT  - ROS
OT  - methyl gallate
OT  - nephropathy
OT  - uric acid
COIS- BX was employd by the company Zhejiang Heze Pharmaceutical Technology Co., Ltd. 
      The remaining authors declare that the research was conducted in the absence of 
      any commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/01/07 06:00
MHDA- 2022/01/07 06:01
PMCR- 2021/12/20
CRDT- 2022/01/06 05:52
PHST- 2021/08/15 00:00 [received]
PHST- 2021/11/22 00:00 [accepted]
PHST- 2022/01/06 05:52 [entrez]
PHST- 2022/01/07 06:00 [pubmed]
PHST- 2022/01/07 06:01 [medline]
PHST- 2021/12/20 00:00 [pmc-release]
AID - 759040 [pii]
AID - 10.3389/fphar.2021.759040 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Dec 20;12:759040. doi: 10.3389/fphar.2021.759040. 
      eCollection 2021.