Salvia miltiorrhiza water-soluble extract, but not its constituent salvianolic acid B, abrogates LPS-induced NF-kappaB signalling in intestinal epithelial cells.
Herbal medicine has become an increasing popular therapeutic alternative among patients suffering from various inflammatory disorders. The Salvia miltiorrhizae water-soluble extract (SME) have been shown to possess antioxidant and anti-inflammatory properties in vitro. However, the mechanism of action and impact of SME on LPS-induced gene expression is still unknown. We report that SME significantly abrogated LPS-induced IkappaB phosphorylation/degradation, NF-kappaB transcriptional activity and ICAM-1 gene expression in rat IEC-18 cells. Chromatin immunoprecipitation assay demonstrated that LPS-induced RelA recruitment to the ICAM-1 gene promoter was inhibited by SME. Moreover, in vitro kinase assay showed that SME directly inhibits LPS induced IkappaB kinase (IKK) activity in IEC-18 cells. To investigate the physiological relevance of SME inhibitory activity on NF-kappaB signalling, we used small intestinal explants and primary intestinal epithelial cells derived from a transgenic mouse expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-kappaB cis-elements (cis-NF-kappaB(EGFP)). SME significantly blocked LPS-induced EGFP expression and IkappaBalpha phosphorylation in intestinal explants and primary IECs, respectively. However, salvianolic acid B, an activate component of SME did not inhibit NF-kappaB transcriptional activity and IkappaB phosphorylation/degradation in IEC-18 cells. These results indicate that SME blocks LPS-induced NF-kappaB signalling pathway by targeting the IKK complex in intestinal epithelial cells. Modulation of bacterial product-mediated NF-kappaB signalling by natural plant extracts may represent an attractive strategy towards the prevention and treatment of intestinal inflammation.
Kim
J S
JS
Department of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Narula
A S
AS
Jobin
C
C
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D027561:Salvia miltiorrhiza; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility; D014178:Translocation, Genetic; D014867:Water; D053630:Depsides
D001572:Benzofurans; D004365:Drugs, Chinese Herbal; D020672:I-kappa B Proteins; D018799:Intercellular Adhesion Molecule-1; D008070:Lipopolysaccharides; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D012333:RNA, Messenger; D014867:Water; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; C076944:salvianolic acid B; D053630:Depsides