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.
Natural Products Research Institute, College of Pharmacy, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-742, Republic of Korea.
Eun Myoung
EM
Shin
Hong Yu
HY
Zhou
Guang Hua
GH
Xu
Seung Ho
SH
Lee
Irmgard
I
Merfort
Yeong Shik
YS
Kim
D019342:Acetic Acid / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification* / Q000494:pharmacology* / Q000627:therapeutic use; D002199:Capillary Permeability / Q000187:drug effects; D002351:Carrageenan / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020672:I-kappa B Proteins / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D032104:Poncirus / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014315:Triterpenes / Q000302:isolation & purification* / Q000494:pharmacology* / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014315:Triterpenes; C548350:hispidol A 25-methyl ether; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D002351:Carrageenan; D004247:DNA; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D019342:Acetic Acid