| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 5833082 | International Immunopharmacology | 2013 | 9 Pages |
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.
Graphical abstractDownload full-size imageHighlights⺠Butanol extract of Codonopsis lanceolata (CL) inhibited TNBS-induced colitis in mice. ⺠Echinocystic acid (EA) was a main metabolite of lancemaside A from CL in vivo. ⺠EA potently inhibited inflammation in LPS-stimulated peritoneal macrophages. ⺠Echinocystic acid potently inhibited TNBS-induced colitis in mice.
