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Geniposide is an iridoid glycosides purified from the fruit of Gardenia jasminoides Ellis,which is known to have antiinflammatory,antioxidative and anti-tumor activities.The present study aimed to investigate the effects of geniposide on experimental rat colitis and to reveal the related mechanisms.Experimental rat colitis was induced by rectal administration of a TNBS solution.The rats were treated with geniposide (25,50 mg·kg-1·d-1,ig) or with sulfasalazine (SASP,100 mg·kg1·d-1,ig) as positive control for 14 consecutive days.A Caco-2 cell monolayer exposed to lipopolysaccharides (LPS) was used as an epithelial barrier dysfunction model.Transepithelial electrical resistance (TER) was measured to evaluate intestinal barrier function.In rats with TNBS-induced colitis,administration of geniposide or SASP significantly increased the TNBS-decreased body weight and ameliorated TNBS-induced experimental colitis and related symptoms.Geniposide or SASP suppressed inflammatory cytokine (TNF-α,IL-1β,and IL-6) release and neutrophil infiltration (myeloperoxidase activity) in the colon.In Caco-2 cells,geniposide (25-100 Jg/mL) ameliorated LPS-induced endothelial barrier dysfunction via dose-dependently increasing transepithelial electrical resistance (TER).The results from both in vivo and in vitro studies revealed that geniposide down-regulated NF-KB,COX-2,iNOS and MLCK protein expression,up-regulated the expression of tight junction proteins (occludin and ZO-1),and facilitated AMPK phosphorylation.Both AMPK siRNA transfection and AMPK overexpression abrogated the geniposide-reduced MLCK protein expression,suggesting that geniposide ameliorated barrier dysfunction via AMPK-mediated inhibition of the MLCK pathway.In conclusion,geniposide ameliorated TNBS-induced experimental rat colitis by both reducing inflammation and modulating the disrupted epithelial barrier function via activating the AMPK signaling pathway.