Berberine increases the expression of NHE3 and AQP4 in sennosideA-induced diarrhoea model.
Berberine, a compound isolated from Chinese Goldthread Rhizome, has been widely used as a non-prescription drug to treat diarrhoea in China. Previous studies have demonstrated multiple pharmacological activities for berberine, including its significant role in antimicrobial activity. However, its effect on ion exchange and water transfer remains unclear. The present study aims to explore the effect of berberine on the expression of Na(+)/H(+) exchanger3 (NHE3) and aquaporin4 (AQP4) in both diarrhoea mouse model induced by sennosideA and human intestinal epithelium cell line (HIEC). Semi-quantitative RT-PCR, immunohistochemistry and western blotting were adopted to detect the mRNA and protein expression levels of NHE3 and AQP4. Furthermore, the absorption of berberine and the PKC activity were detected by HPLC and PepTag® Assay to elucidate the underlying mechanisms. It was shown that the expression levels of NHE3 and AQP4 were significantly increased in the diarrhoea mice treated with berberine compared with the untreated diarrhoea mice. Similarly, the expression levels of NHE3 and AQP4 were strikingly enhanced in HIEC co-treated with sennosideA and berberine compared with samples treated with sennosideA only. We also found the maximal absorption of berberine to be approximately 0.01%. In addition, no significant change of PKC activity was observed in the different HIEC treated groups. These results showed that berberine was able to increase the expression of NHE3 and AQP4, suggesting that berberine might exhibit its anti-diarrhoeal effect partially by enhancing the absorption of Na(+) and water.
Department of Gastroenterology and State Key Laboratory of Cancer Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR China.
Yongguo
Y
Zhang
Xin
X
Wang
Sumei
S
Sha
Shuli
S
Liang
Lina
L
Zhao
Lin
L
Liu
Na
N
Chai
Honghong
H
Wang
Kaichun
K
Wu
D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology / Q000627:therapeutic use; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism*; D001599:Berberine / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D039323:Coptis / Q000737:chemistry*; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008517:Phytotherapy; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D027343:Rhizome; D012676:Senna Extract; D000081226:Sennosides; D012964:Sodium / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*; D014867:Water / Q000378:metabolism
D000930:Antidiarrheals; C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; C000613385:SLC9A3 protein, human; D000081226:Sennosides; C000613386:Slc9a3 protein, mouse; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D014867:Water; D001599:Berberine; D012676:Senna Extract; D012964:Sodium; D011493:Protein Kinase C