title: Anti-Neuroinflammatory ent-Kaurane Diterpenoids from Pteris multifida Roots.
abstract: Activated microglia are known to be a major source of cellular neuroinflammation which causes various neurodegenerative diseases, including Alzheimer's disease. In our continuing efforts to search for new bioactive phytochemicals against neuroinflammatory diseases, the 80% methanolic extract ofPteris multifida(Pteridaceae) roots was found to exhibit significant NO inhibitory activity in lipopolysaccharide (LPS)-activated BV-2 microglia cells. Three newent-kaurane diterpenoids, pterokaurane M₁ 2-O-β-d-glucopyranoside (4), 2β,16α-dihydroxy-ent-kaurane 2,16-di-O-β-d-glucopyranoside (10), and 2β,16α,17-trihydroxy-ent-kaurane 2-O-β-d-glucopyranoside (12), were isolated along with nine other known compounds fromP. multifidaroots. The chemical structures of the new compounds were determined by 1D- and 2D-NMR, HR-ESI-MS, and CD spectroscopic data analysis. Among the isolates, compounds1and7significantly inhibited NO production in LPS-stimulated BV-2 cells reducing the expression of the cyclooxygenase-2 (COX-2) protein and the level of pro-inflammatory mediators such as prostaglandin E₂ (PGE₂), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. These results suggest thatent-kaurane diterpenes fromP. multifidacould be potential lead compounds that act as anti-neuroinflammatory agents.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 08826, Korea. jkim11@snu.ac.kr.
authors.forename: Jung Wha
authors.initials: JW
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 08826, Korea. quftkfka@gmail.com.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Seo
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 08826, Korea. wkoh1@snu.ac.kr.
authors.forename: Won Keun
authors.initials: WK
authors.lastname: Oh
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 08826, Korea. shsung@snu.ac.kr.
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Sung
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D045786:Diterpenes, Kaurane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007249:Inflammation; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000432:Methanol / Q000737:chemistry; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010936:Plant Extracts / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D032495:Pteris / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D000093242:Interleukin-6 Inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D045786:Diterpenes, Kaurane; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000432:Methanol; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D010936:Plant Extracts; D012997:Solvents; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C587672:IL1B protein, mouse; C508600:IL6 protein, human; C077623:Ptgs2 protein, mouse
keywords: BV-2 microglia; Pteris multifida; anti-neuroinflammation; ent-kaurane diterpenoids; nitric oxide (NO)