In vitro anti-inflammatory activity of 23-hydroxyursolic acid isolated from Cussonia bancoensis in murine macrophage RAW 264.7 cells.
In the present study, the effects of various triterpenoids isolated from the stem bark of Cussonia bancoensis, namely, ursolic acid ( 1), 23-hydroxyursolic acid ( 2), 3-O-alpha- L-arabinopyranosyl-23-hydroxyursolic acid (3), and 3-O-beta-D-glucopyranosyl-23-hydroxyursolic acid ( 4) were evaluated on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E (2) (PGE (2)) release by the macrophage cell line RAW 264.7. Of the tested triterpenoids, 23-hydroxyursolic acid ( 2) was found to be the most potent inhibitor of NO production, and also significantly reduced PGE (2) release. Consistent with these observations, the protein and mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 enzymes were inhibited by 23-hydroxyursolic acid ( 2) in a concentration-dependent manner. Furthermore, 23-hydroxyursolic acid ( 2) inhibited the LPS-induced DNA binding activity of nuclear factor- kappaB (NF- kappaB), which was associated with a decrease of p65 protein levels in the nucleus. These results suggest that the 23-hydroxyursolic acid-mediated inhibition of iNOS and COX-2 expression, via blocking NF- kappaB activation, may mechanistically responsible for the anti-inflammatory effects of Cussonia bancoensis stem bark in vitro.
Shin
Kyung-Min
KM
College of Pharmacy, Kyung-Hee University, Dongdaemun-Ku, Hoegi-Dong 130-701, Seoul, Korea.
Kim
Rung-Kyu
RK
Azefack
Tapondjou Leon
TL
David
Lontsi
L
Luc
Sondengam Beibam
SB
Choudhary
Muhammad Iqbal
MI
Park
Hee-Juhn
HJ
Choi
Jong-Won
JW
Lee
Kyung-Tae
KT
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D027481:Araliaceae; D002460:Cell Line / Q000187:drug effects; D051546:Cyclooxygenase 2; D017931:DNA Primers; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000187:drug effects; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018547:Plant Stems; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017931:DNA Primers; D007527:Isoenzymes; D008070:Lipopolysaccharides; D010936:Plant Extracts; D012333:RNA, Messenger; D014315:Triterpenes; C469884:23-hydroxyursolic acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone