ent-kaurane diterpenoids from Croton tonkinensis inhibit LPS-induced NF-κB activation and NO production

Four ent-kaurane diterpenoids including two known, ent-7alpha,14beta-dihydroxykaur-16-en-15-one (1) and ent-18-acetoxy-7alpha-hydroxykaur-16-en-5-one (2), and two new, ent-1beta-acetoxy-7alpha,14beta-dihydroxykaur-16-en-15-one (3) and ent-18-acetoxy-7alpha,14beta-dihydroxykaur-16-en-15-one (4), were isolated from the leaves of Croton tonkinensis in a search for inhibitors of NF-B-K activation and nitric oxide production. These ent-kauranoids inhibited LPS-induced NF-B-K activation in murine macrophage RAW264.7 cells at IC50 values between 0.07 and 0.42 muM. Consistently, the ent-kauranoids markedly reduced LPS-induced NO production in a comparable concentration-dependent manner.