Serratane triterpenoids isolated from Lycopodium clavatum by bioactivity-guided fractionation attenuate the production of inflammatory mediators.
Kľúčové slová
Abstrakt
Lycopodium clavatum has been used in traditional medicine for the treatment of kidney disorders, rheumatic arthritis, cystitis, and gastritis. We isolated a new serratane triterpenoid (2), and five known triterpenoids (1, 3-6) from the ethyl acetate fraction of L. clavatum by bioactivity-guided fractionation based on their suppression of inflammatory cytokines. Two different cell lines, RAW 264.7 and HT-29 were used to determine the anti-inflammatory activity of the isolated compounds. Among them, compounds 1, 2, 4, and 5 significantly inhibited the production of lipopolysaccharide (LPS)-induced NO in macrophages. Compounds 1, 2, 4, and 5 reduced inducible nitric oxide (iNOS) expression in RAW 264.7 cells and compounds 1 and 6 downregulated COX-2, which correlated with the reduced expression of PGE2. Compounds 1, 2, 4, and 5 downregulated pro-inflammatory cytokines, such as interleukin-1β (IL-1β) in macrophages, and additionally suppressed the levels of IL-8 in HT-29 cells. To determine the signaling pathways involved in the suppression of NO production by these compounds, we investigated ERK1/2 and nuclear factor-kappa B (NF-κB) expression by western blot analysis. We observed that these compounds downregulated the expression of LPS-induced NF-κB and pERK 1/2 in RAW 264.7 cells. Our results demonstrate that serratane triterpenoids isolated from L. clavatum may be used as potential candidates for treating inflammatory bowel disease (IBD) due to their anti-inflammatory effects.