Biginkgosides A-I, Unexpected Minor Dimeric Flavonol Diglycosidic Truxinate and Truxillate Esters from Ginkgo biloba Leaves and Their Antineuroinflammatory and Neuroprotective Activities

Guang-Lei Ma; Juan Xiong; Guo-Xun Yang; Li-Long Pan; Chang-Ling Hu; Wei Wang; Hui Fan; Qiu-Hua Zhao; Hai-Yan Zhang; Jin-Feng Hu

doi:10.1021/acs.jnatprod.6b00061

Biginkgosides A-I, Unexpected Minor Dimeric Flavonol Diglycosidic Truxinate and Truxillate Esters from Ginkgo biloba Leaves and Their Antineuroinflammatory and Neuroprotective Activities

J Nat Prod. 2016 May 27;79(5):1354-64. doi: 10.1021/acs.jnatprod.6b00061. Epub 2016 May 3.

Authors

Guang-Lei Ma, Juan Xiong, Guo-Xun Yang, Li-Long Pan, Chang-Ling Hu, Wei Wang¹, Hui Fan², Qiu-Hua Zhao², Hai-Yan Zhang¹, Jin-Feng Hu

Affiliations

¹ 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.
² School of Chemistry and Molecular Engineering, East China Normal University , No. 500 Dongchuan Road, Shanghai 200241, People's Republic of China.

PMID: 27140807
DOI: 10.1021/acs.jnatprod.6b00061

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid beta-Peptides / drug effects
Amyloid beta-Peptides / pharmacology*
Cell Survival / drug effects
Drugs, Chinese Herbal / chemistry
Drugs, Chinese Herbal / isolation & purification*
Drugs, Chinese Herbal / pharmacology*
Esters
Flavonols / chemistry
Flavonols / isolation & purification*
Flavonols / pharmacology*
Ginkgo biloba / chemistry*
Glycosides / chemistry
Glycosides / isolation & purification*
Glycosides / pharmacology*
Lipopolysaccharides / pharmacology
Macrophages / metabolism
Molecular Structure
Neuroblastoma / drug therapy
Neuroprotective Agents / chemistry
Neuroprotective Agents / isolation & purification
Neuroprotective Agents / pharmacology*
Nitric Oxide / biosynthesis
Nuclear Magnetic Resonance, Biomolecular
Peptide Fragments / drug effects
Plant Extracts / pharmacology
Plant Leaves / chemistry*

Substances

Amyloid beta-Peptides
Drugs, Chinese Herbal
Esters
Flavonols
Glycosides
Lipopolysaccharides
Neuroprotective Agents
Peptide Fragments
Plant Extracts
amyloid beta-protein (25-35)
Nitric Oxide