Anti-inflammatory activity of prosapogenin methyl ester of platycodin D via nuclear factor-kappaB pathway inhibition.
Platycodin D (PD) isolated from Platycodi Radix has been reported to have anti-inflammatory and anti-tumor activities. In this study, we have investigated anti-inflammatory activities of prosapogenin D (PrsD) and prosapogenin D methyl ester (PrsDMe) of PD. The results indicated that PrsDMe concentration-dependently inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production, however, PrsD did not inhibit NO production in LPS-induced macrophages. Furthermore, PrsDMe inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) without appreciable cytotoxic effects. In the transfectant RAW 264.7 cells, PrsDMe was observed to reduce the level of nuclear factor-kappaB (NF-kappaB) activity. PrsDMe also inhibited the degradation of an inhibitory protein called inhibitor kappaB (IkappaB). Therefore, it was suggested that PrsDMe inhibited the expression of LPS-induced iNOS and COX-2 genes by suppressing NF-kappaB activation at the transcriptional level. Also, PrsDMe showed carrageenan-induced acute anti-inflammatory activity and the adjuvant-induced anti-arthritic activity in mice. In conclusion, we suggest that these compounds exert an anti-inflammatory effect through the regulation of the NF-kappaB pathway. The different activities of PD, PrsD and PrsDMe are based on the structure of the sugar substituent or methyl group at the C28-carboxyl position.
Chung
Ji Won
JW
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Korea.
Noh
Eun Jung
EJ
Zhao
Hai Lin
HL
Sim
Joon-Soo
JS
Ha
Young Wan
YW
Shin
Eun Myoung
EM
Lee
Eun Bang
EB
Cheong
Choon Sik
CS
Kim
Yeong Shik
YS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004487:Edema / Q000188:drug therapy / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D017930:Genes, Reporter; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D031238:Platycodon / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D014162:Transfection; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012503:Saponins; D014315:Triterpenes; C533997:prosapogenin D methyl ester; D009569:Nitric Oxide; C026473:prosapogenin; C108953:platycodin D; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone