title: Inhibition of nuclear transcription factor-κB and activation of peroxisome proliferator-activated receptors in HepG2 cells by cucurbitane-type triterpene glycosides from Momordica charantia.
abstract: Momordica charantia is used to treat various diseases, including inflammatory conditions. Previous reports indicated that the extract of this plant inhibits activation of nuclear transcription factor-κB (NF-κB) but activates peroxisome proliferator-activated receptor (PPAR). Additionally, cucurbitane-type triterpene glycosides are the main bioactive components of the fruit of M. charantia. Therefore, we investigated the anti-inflammatory activity of 17 cucurbitane-type triterpene glycosides (1-17) isolated from this plant. Their inhibition of NF-κB and activation of PPAR activities in HepG2 cells were measured using luciferase reporter and PPAR subtype transactivation assays. Compounds 6 and 8 were found to inhibit NF-κB activation stimulated by tumor necrosis factor-α (TNFα) in a dose-dependent manner. With 50% inhibition concentration (IC(50)) values of 0.4 μM, compounds 6 and 8 were more potent inhibitors than the positive control, sulfasalazine (IC(50)=0.9 μM). Compounds 4, 6, and 8 also inhibited TNFα-induced expressions of inducible nitric oxide synthase and cyclooxygenase-2 mRNA. However, only compound 13 significantly increased PPARγ transactivation.
authors.affiliation: College of Pharmacy, Chungnam National University, Daejeon, Korea.
authors.forename: Nguyen Xuan
authors.initials: NX
authors.lastname: Nhiem
authors.forename: Pham Hai
authors.initials: PH
authors.lastname: Yen
authors.forename: Nguyen Thi Thanh
authors.initials: NT
authors.lastname: Ngan
authors.forename: Tran Hong
authors.initials: TH
authors.lastname: Quang
authors.forename: Phan Van
authors.initials: PV
authors.lastname: Kiem
authors.forename: Chau Van
authors.initials: CV
authors.lastname: Minh
authors.forename: Bui Huu
authors.initials: BH
authors.lastname: Tai
authors.forename: Nguyen Xuan
authors.initials: NX
authors.lastname: Cuong
authors.forename: Seok Bean
authors.initials: SB
authors.lastname: Song
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006027:Glycosides / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008156:Luciferases / Q000378:metabolism; D029777:Momordica charantia / Q000737:chemistry*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D006027:Glycosides; D016328:NF-kappa B; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D010936:Plant Extracts; D012333:RNA, Messenger; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C514277:cucurbitane; D008156:Luciferases; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human