Anti-inflammatory activity of hispidol A 25-methyl ether, a triterpenoid isolated from Ponciri Immaturus Fructus

The anti-inflammatory activity of hispidol A 25-methyl ether (hispidol A 25-Me ether), a triterpenoid isolated from Ponciri Immaturus Fructus, was studied in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages. It was revealed that hispidol A 25-Me ether dose-dependently inhibits nitric oxide (NO) production by down-regulating inducible nitric oxide synthase (iNOS). It also reduces prostaglandin E(2) (PGE(2)) production by inhibiting cyclooxygenase-2 (COX-2) expression proven on both mRNA as well as on protein levels. In addition, hispidol A 25-Me ether inhibits mRNA expressions of major pro-inflammatory cytokines including the tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6). Interestingly, hispidol A 25-Me ether probably exhibits a glucocorticoid-like activity, exerting functional inhibition of NF-kappaB without inhibition of DNA binging as de novo synthesis of IkappaB-alpha was induced and thereby NF-kappaB activity was reduced. Furthermore, administrations of hispidol A 25-Me ether (1 and 10mg/kg, i.p., v/w.) were tested in two animal experiments involving acute inflammation, namely, the carrageenan-induced paw edema swelling test and the acetic acid-induced vascular permeability assay, and showed concentration-related inhibitory activities. The anti-inflammatory property of hispidol A 25-Me ether seems to resemble the effects of the class of naturally occurring anti-inflammatory agents, glucocorticoids, which inhibit transcriptions of important inflammatory mediators.