Echinocystic acid, a metabolite of lancemaside A, inhibits TNBS-induced colitis in mice.
The rhizome of Codonopsis lanceolata (CL, family Campanulaceae), of which the main constituent is lancemaside A, has been used for cough and bronchitis in traditional Chinese medicine. To evaluate anti-colitic effect of CL, we examined anti-inflammatory effect of CL extracts, lancemaside A and its metabolites in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitic mice. Among CL extracts, CL BuOH extract inhibited LPS-induced IL-1β, IL-6 and TNF-α expression, as well as NF-κB activation most potently. CL BuOH extract also inhibited colon shortening and myeloperoxidase activity in TNBS-induced colitic mice. Among lancemaside A, a main constituent of CL BuOH extract, and its metabolites (lancemaside X, echinocystic acid-3-O-β-d-glucopyranoside and echinocystic acid), echinocystic acid inhibited the expression of the pro-inflammatory cytokines, IL-1β, IL-6, and TNF-α, as well as the phosphorylation of IKKβ and p65 in LPS-stimulated peritoneal macrophages most potently. Echinocystic acid also potently inhibited the binding of LPS to TLR4 on peritoneal macrophages. Lancemaside A and its metabolite, echinocystic acid, inhibited TNBS-induced colonic inflammation, including colon shortening, increased myeloperoxidase activity and pro-inflammatory cytokine expression, and NF-κB activation in mice. The anti-colitic effect of echinocystic acid was superior to that of lancemaside A. Based on these findings, orally administered lancemaside A may be metabolized to echinocystic acid, which may express anti-colitic effect by inhibiting the binding of LPS to TLR4 on the macrophages.
Department of Life and Nanopharmaceutical Sciences and Department of Pharmaceutical Science, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
Supriya R
SR
Hyam
Se-Eun
SE
Jang
Jin-Ju
JJ
Jeong
Eun-Ha
EH
Joh
Myung Joo
MJ
Han
Dong-Hyun
DH
Kim
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002478:Cells, Cultured; D029745:Codonopsis / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011485:Protein Binding / Q000187:drug effects; D027343:Rhizome; D012503:Saponins / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012503:Saponins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C533150:lancemaside A; D009828:Oleanolic Acid; D014302:Trinitrobenzenesulfonic Acid; C022999:echinocystic acid