PMID- 37811696
OWN - NLM
STAT- MEDLINE
DCOM- 20231122
LR  - 20231122
IS  - 1742-7843 (Electronic)
IS  - 1742-7835 (Linking)
VI  - 133
IP  - 6
DP  - 2023 Dec
TI  - Berberine ameliorates renal interstitial inflammation and fibrosis in mice with 
      unilateral ureteral obstruction.
PG  - 757-769
LID - 10.1111/bcpt.13947 [doi]
AB  - Berberine acts via multiple pathways to alleviate fibrosis in various tissues and 
      shows renoprotective effects. However, its role and underlying mechanisms in 
      renal fibrosis remain unclear. Herein, we aimed to investigate the protective 
      effects and molecular mechanisms of berberine against unilateral ureteric 
      obstruction-induced renal fibrosis. The results indicated that berberine 
      treatment (50 mg/kg/day) markedly alleviated histopathological alterations, 
      collagen deposition and inflammatory cell infiltration in kidney tissue and 
      restored mouse renal function. Mechanistically, berberine intervention inhibited 
      NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome 
      activation and the levels of the inflammatory cytokine IL-1beta in the kidneys of 
      unilateral ureteric obstruction mice. In addition, berberine relieved unilateral 
      ureteric obstruction-induced renal injury by activating adenosine 
      monophosphate-activated protein kinase (AMPK) signalling and promoting fatty acid 
      beta-oxidation. In vitro models showed that berberine treatment prevented the 
      TGF-beta1-induced profibrotic phenotype of hexokinase 2 (HK-2) cells, characterized 
      by loss of an epithelial phenotype (alpha smooth muscle actin [alpha-SMA]) and 
      acquisition of mesenchymal marker expression (E-cadherin), by restoring abnormal 
      fatty acid beta-oxidation and upregulating the expression of the fatty acid 
      beta-oxidation related-key enzymes or regulators (phosphorylated-AMPK, peroxisome 
      proliferator activated receptor alpha [PPARalpha] and carnitine palmitoyltransferase 
      1A [CPT1A]). Collectively, berberine alleviated renal fibrosis by inhibiting 
      NLRP3 inflammasome activation and protected tubular epithelial cells by reversing 
      defective fatty acid beta-oxidation. Our findings might be exploited clinically to 
      provide a potential novel therapeutic strategy for renal fibrosis.
CI  - (c) 2023 The Authors. Basic & Clinical Pharmacology & Toxicology published by John 
      Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT 
      (former Nordic Pharmacological Society).
FAU - Tan, Enxue
AU  - Tan E
AUID- ORCID: 0000-0002-6370-2689
AD  - Department of Nephrology, Second Hospital, Shanxi Medical University, Taiyuan, 
      China.
FAU - Gao, Zhihong
AU  - Gao Z
AD  - Department of Nephrology, Shanxi Bethune Hospital, Taiyuan, China.
FAU - Wang, Qian
AU  - Wang Q
AD  - Department of Nephrology, Second Hospital, Shanxi Medical University, Taiyuan, 
      China.
FAU - Han, Baosheng
AU  - Han B
AD  - Department of Cardiac Surgery, Shanxi Cardiovascular Hospital, Taiyuan, China.
FAU - Shi, Honghong
AU  - Shi H
AD  - Department of Nephrology, Second Hospital, Shanxi Medical University, Taiyuan, 
      China.
FAU - Wang, Lihua
AU  - Wang L
AD  - Department of Nephrology, Second Hospital, Shanxi Medical University, Taiyuan, 
      China.
FAU - Zhu, Guozhen
AU  - Zhu G
AD  - Department of Nephrology, Second Hospital, Shanxi Medical University, Taiyuan, 
      China.
FAU - Hou, Yanjuan
AU  - Hou Y
AUID- ORCID: 0000-0002-5197-7394
AD  - Department of Nephrology, Second Hospital, Shanxi Medical University, Taiyuan, 
      China.
LA  - eng
GR  - 81900670/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20231018
PL  - England
TA  - Basic Clin Pharmacol Toxicol
JT  - Basic & clinical pharmacology & toxicology
JID - 101208422
RN  - 0I8Y3P32UF (Berberine)
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Fatty Acids)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Ureteral Obstruction/complications/drug therapy
MH  - *Berberine/pharmacology/therapeutic use/metabolism
MH  - Inflammasomes/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - AMP-Activated Protein Kinases/metabolism
MH  - *Kidney Diseases/drug therapy/etiology/prevention & control
MH  - Kidney
MH  - Transforming Growth Factor beta1/metabolism
MH  - Inflammation/pathology
MH  - Fibrosis
MH  - Fatty Acids/metabolism/pharmacology/therapeutic use
OTO - NOTNLM
OT  - NLRP3 inflammasome
OT  - berberine
OT  - fatty acid beta-oxidation
OT  - fibrosis
OT  - renal tubular epithelial cells
EDAT- 2023/10/09 12:43
MHDA- 2023/11/22 06:44
CRDT- 2023/10/09 06:42
PHST- 2023/07/26 00:00 [revised]
PHST- 2023/02/12 00:00 [received]
PHST- 2023/08/01 00:00 [accepted]
PHST- 2023/11/22 06:44 [medline]
PHST- 2023/10/09 12:43 [pubmed]
PHST- 2023/10/09 06:42 [entrez]
AID - 10.1111/bcpt.13947 [doi]
PST - ppublish
SO  - Basic Clin Pharmacol Toxicol. 2023 Dec;133(6):757-769. doi: 10.1111/bcpt.13947. 
      Epub 2023 Oct 18.