当前位置： SCI文献检索 > PHARMACOLOGICAL RESEARCH期刊下所有文献 > Curcumin and allopurinol ameliorate fructose-induced hepatic inflammation in rats via miR-200a-mediated TXNIP/NLRP3 inflammasome inhibition.

Curcumin and allopurinol ameliorate fructose-induced hepatic inflammation in rats via miR-200a-mediated TXNIP/NLRP3 inflammasome inhibition.

Abstract：

:Excess fructose consumption causes high prevalence of metabolic syndrome and inflammatory liver diseases. The aim of the current study was to investigate the therapeutic effects and underlying molecular mechanisms of curcumin and allopurinol in high fructose-induced hepatic inflammation. Male Sprague-Dawley rats were supplied with standard rat chow and drinking water containing 10% (w/v) fructose for consecutive 12 weeks. Curcumin (15, 30 and 60 mg/kg) and allopurinol (5 mg/kg) were administered to rats via oral gavage daily from Week 7 to 12. For in vitro experiments, curcumin (2.5 μM) and allopurinol (100 μM) were treated to 5 mM fructose-exposed Buffalo rat liver cell line (BRL-3 A) and human hepatoblastoma cell line (HepG2), respectively. The data from these animal and hepatocyte models showed that curcumin and allopurinol ameliorated fructose-induced metabolic symptom, especially hepatic inflammation in rats. Interestingly, down-regulation of microRNA-200a (miR-200a) was screened out in livers of fructose-fed rats and then validated in fructose-exposed BRL-3 A and HepG2 cells. Fructose-induced miR-200a low-expression was identified as a negative mediator of thioredoxin interacting protein (TXNIP) by direct targeting of 3'UTR-rTXNIP, subsequently activating the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in BRL-3 A cells. Curcumin, as well as allopurinol, notably up-regulated miR-200a expression, accordingly, down-regulated TXNIP and inhibited NLRP3 inflammasome activation in fructose-fed rat livers and fructose-exposed BRL-3 A and HepG2 cells. Taken together, this study firstly identified miR-200a as a biomarker of fructose-induced hepatic inflammation, and revealed the hepatoprotection of curcumin and allopurinol via up-regulating miR-200a-mediated TXNIP/NLRP3 inflammasome pathway.

journal_name

Pharmacol Res

journal_title

Pharmacological research

authors

Ding XQ,Wu WY,Jiao RQ,Gu TT,Xu Q,Pan Y,Kong LD

doi

10.1016/j.phrs.2018.09.021

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

64-75

eissn

1043-6618

issn

1096-1186

pii

S1043-6618(18)30828-4

journal_volume

137

pub_type

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