title: Inhibition of Nitric Oxide Production in BV2 Microglial Cells by Triterpenes from Tetrapanax papyriferus.
abstract: It is well known that activated microglia produce nitric oxide (NO), which has an important role in the pathophysiology of several neurodegenerative diseases such as Alzheimer's disease. In the course of searching for novel therapeutic agents from medicinal plants against neuroinflammatory diseases, the methanolic extract of Tetrapanax papyriferus was found to have significant NO inhibitory activity in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. Nine oleanane-type triterpenes, including two new compounds, epipapyriogenin C-3-O-β-d-glucopyranoside (6) and 11-O-butylpapyrioside LIIc (9), were isolated from the leaves and stems of Tetrapanax papyriferus. The structures of these compounds were elucidated with 1D- and 2D-NMR and MS data. Among these Δ(11,13) oleanane-type triterpenes, compound 3 showed significant NO inhibitory activity in BV-2 cells, reducing the LPS-induced expression of COX-2 and pro-inflammatory cytokines such as TNF-α and IL-6. Compounds 7 and 9 also showed NO inhibitory activities among the Δ(12) oleanane-type triterpene saponins. These results show that oleanane-type triterpenes isolated from T. papyriferus could be a potential natural resource of NO inhibitors used in the treatment of neurodegenerative disorders.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 151-742, Korea. cnamki@naver.com.|Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. cnamki@naver.com.
authors.forename: Namki
authors.initials: N
authors.lastname: Cho
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 151-742, Korea. arsinoe@snu.ac.kr.
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Moon
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 151-742, Korea. kimkami2@snu.ac.kr.
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. jaewoo.hong@nih.gov.
authors.forename: Jaewoo
authors.initials: J
authors.lastname: Hong
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. beutlerj@mail.nih.gov.
authors.forename: John A
authors.initials: JA
authors.lastname: Beutler
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 151-742, Korea. shsung@snu.ac.kr.
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Sung
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry*; D027481:Araliaceae / Q000737:chemistry; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008070:Lipopolysaccharides / Q000633:toxicity; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000737:chemistry* / Q000302:isolation & purification; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D010936:Plant Extracts; D009569:Nitric Oxide; D009828:Oleanolic Acid; D051546:Cyclooxygenase 2
keywords: BV2 microglial cells; COX-2; NO; Tetrapanax papyriferus; triterpenes