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Berberine induces ZIP14 expression and modulates zinc redistribution to protect intestinal mucosal barrier during polymicrobial sepsis

He, Yan, Yuan, Xiaoming, Zuo, Hao, Li, Xiangwei, Sun, Ying, Feng, Aiwen
Life sciences 2019 v.233 pp. 116697
Limulus amebocyte lysate assay, berberine, electrical resistance, endotoxins, gene expression, gluconates, human cell lines, insulin-like growth factor I, intestinal mucosa, lipopolysaccharides, messenger RNA, models, occludins, permeability, protein synthesis, quantitative polymerase chain reaction, rats, reverse transcriptase polymerase chain reaction, sepsis (infection), spectrophotometers, survival rate, tight junctions, zinc
The present study investigated if berberine might induce Zrt-Irt-like protein 14 (ZIP14) and affect zinc redistribution to protect intestinal barrier in sepsis.Rodent model of sepsis was induced by cecal ligation and puncture (CLP). Plasma endotoxin was assayed by LAL test and plasma zinc was measured by flame atomic spectrophotometer. Gut mucosal permeability was determined by plasma FITC-dextran. Zinc content and ZIP14 mRNA in gut mucosa were assayed by spectrophotometer and qRT-PCR, respectively. Tight junction integrity of Caco-2 was evaluated by transepithelial electrical resistance (TEER). Tight junction (TJ) protein expression was detected by Western blotting.Berberine and zinc gluconate pretreatment to CLP rats improved survival rate, reduced plasma endotoxin level, alleviated hypozincemia, increased zinc accumulation and ZIP14 mRNA expression in the intestinal mucosa. Berberine and zinc gluconate pretreatment decreased CLP-elicited intestinal hyperpermeability to FITC-dextran. These effects of berberine in vivo were abolished by AG1024. In vitro, lipopolysaccharide (LPS) repressed zinc transfer into Caco-2 cells exposed to zinc gluconate. Berberine and IGF-I treatment increased ZIP14 protein expression and promoted zinc transfer into Caco-2 cells exposed to zinc gluconate plus LPS. Berberine treatment induced TJ protein (claudin-1 and occludin) and raised TEER in LPS-treated Caco-2 cells. These effects of berberine in vitro were partially inhibited by ZIP14 siRNA.The present study reveals that berberine induces ZIP14 expression and affects zinc re- distribution to protect intestinal barrier in sepsis, which is partially linked with the activation of IGF-I signaling.