title: Biginkgosides A-I, Unexpected Minor Dimeric Flavonol Diglycosidic Truxinate and Truxillate Esters from Ginkgo biloba Leaves and Their Antineuroinflammatory and Neuroprotective Activities.
abstract: Nine unexpected new flavonol glycoside cyclodimers in the truxinate (1-7, biginkgosides A-G, respectively) or truxillate [biginkgosides H (8) and I (9)] forms were isolated as minor components from the extract of Ginkgo biloba leaves. The new dimers possess an unusual cyclobutane ring formed by a [2+2]-cycloaddition between two symmetric (for compounds 1-5 and 7-9) or nonsymmetric (for 6) flavonol coumaroyl glucorhamnosides. A plausible biosynthetic pathway for these new compounds based on the frontier molecular orbital theory of cycloaddition reactions is briefly discussed. An antineuroinflammatory screening revealed that biginkgosides E (5) and H (8) inhibited nitric oxide production in lipopolysaccharide-activated BV-2 microglial cells, with IC50 values of 2.91 and 17.23 μM, respectively. Additionally, biginkgoside F (6) showed a significant neuroprotective effect (34.3% increase in cell viability at 1 μM) against Aβ25-35-induced cell viability decrease in SH-SY5Y neuroblastoma cells.
authors.forename: Guang-Lei
authors.initials: GL
authors.lastname: Ma
authors.forename: Juan
authors.initials: J
authors.lastname: Xiong
authors.forename: Guo-Xun
authors.initials: GX
authors.lastname: Yang
authors.forename: Li-Long
authors.initials: LL
authors.lastname: Pan
authors.forename: Chang-Ling
authors.initials: CL
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , No. 555 Zuchongzhi Road, Shanghai 201203, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University , No. 500 Dongchuan Road, Shanghai 200241, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fan
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University , No. 500 Dongchuan Road, Shanghai 200241, People's Republic of China.
authors.forename: Qiu-Hua
authors.initials: QH
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , No. 555 Zuchongzhi Road, Shanghai 201203, People's Republic of China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Zhang
authors.forename: Jin-Feng
authors.initials: JF
authors.lastname: Hu
mesh_terms: D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004952:Esters; D044948:Flavonols / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D020441:Ginkgo biloba / Q000737:chemistry*; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D015394:Molecular Structure; D009447:Neuroblastoma / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D004365:Drugs, Chinese Herbal; D004952:Esters; D044948:Flavonols; D006027:Glycosides; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010936:Plant Extracts; C074636:amyloid beta-protein (25-35); D009569:Nitric Oxide