title: Chikusetsusaponin IVa Methyl Ester Isolated from the Roots of Achyranthes japonica Suppresses LPS-Induced iNOS, TNF-α, IL-6, and IL-1β Expression by NF-κB and AP-1 Inactivation.
abstract: We investigated the effect of chikusetsusaponin IVa (CS) and chikusetsusaponin IVa methyl ester (CS-ME) from the roots of Achyranthes japonica NAKAI on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW264.7 macrophages. CS-ME more potently inhibited LPS-induced NO and PGE2 production than CS. CS-ME concentration-dependently inhibited LPS-induced tumor necrosis factor (TNF)-α and interleukin (IL)-6 and IL-1β production in RAW264.7 macrophages and mouse peritoneal macrophages. Consistent with these findings, CS-ME suppressed LPS-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 at protein level as well as iNOS, COX-2, TNF-α, IL-6, and IL-1β at mRNA level. In addition, CS-ME suppressed LPS-induced transcriptional activity of nuclear factor (NF)-κB and activator protein (AP)-1. The anti-inflammatory properties of CS-ME might result from suppression of iNOS, COX-2, TNF-α, IL-6, and IL-1β expression through downregulation of NF-κB and AP-1 in macrophages.
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University.
authors.forename: Hae-Jun
authors.initials: HJ
authors.lastname: Lee
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Shin
authors.forename: Woo-Seok
authors.initials: WS
authors.lastname: Lee
authors.forename: Heon-Yong
authors.initials: HY
authors.lastname: Shim
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Park
authors.forename: Dae-Sik
authors.initials: DS
authors.lastname: Jang
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
mesh_terms: D029044:Achyranthes; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004952:Esters / Q000302:isolation & purification / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D000067996:RAW 264.7 Cells; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004952:Esters; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012503:Saponins; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C098580:chikusetsu saponin IVa; D009828:Oleanolic Acid; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone