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.