title: Berberine ameliorates COX-2 expression in rat small intestinal mucosa partially through PPARγ pathway during acute endotoxemia.
abstract: Berberine hydrochloride (BBR), a plant alkaloid, has been used to treat intestinal inflammation or infection for years. Cyclooxygenase-2 (COX-2) is pro-inflammatory mediator and involved in the induction of gut inflammation. The expression of COX-2 in small bowel mucosa was determined and the mechanism by which BBR modulated COX-2 expression was explored in a rat model of endotoxemia induced by lipopolysaccharide (LPS). The results showed that without LPS stimulation COX-2 was constitutively expressed at low levels in control rats. LPS challenge rapidly induced COX-2 gene transcription resulting in high levels of inducible COX-2 expression in endotoxemic rats. BBR pre- and post-treatment had no marked effect on constitutive COX-2 expression but inhibited inducible COX-2 overexpression. LPS challenge increased the expression and phosphorylation of peroxisome proliferator-activated receptor gamma (PPARγ), p38 and activating transcription factor 2 and 3 (ATF2, ATF3), but the effects of LPS were inhibited by BBR treatment. GW9662 did not influence constitutive COX-2 expression but enhanced inducible COX-2 overproduction. Besides, GW9662 abolished the inhibitory effect of BBR on inducible COX-2, p38, ATF2, 3 expression and phosphorylation. Collectively, these results indicated that BBR gavage could attenuate the overexpression of inducible COX-2, not constitutive COX-2, in ileal mucosa during acute endotoxemia in part via activation of PPARγ pathway, which negatively interfered with p38/ATFs cascade.
authors.affiliation: Research Institute of General Surgery, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Road, Nanjing 210002, China.
authors.forename: Ai-Wen
authors.initials: AW
authors.lastname: Feng
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.forename: Guang-Rong
authors.initials: GR
authors.lastname: Zhou
authors.forename: Ren
authors.initials: R
authors.lastname: Yu
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Xin-Li
authors.initials: XL
authors.lastname: Huang
authors.forename: Qiu-Rong
authors.initials: QR
authors.lastname: Li
authors.forename: Jie-Shou
authors.initials: JS
authors.lastname: Li
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism*; D004926:Escherichia coli; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; D047495:PPAR gamma; D012333:RNA, Messenger; D001599:Berberine; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat