title: Quantitative analysis of the flavonoid glycosides and terpene trilactones in the extract of Ginkgo biloba and evaluation of their inhibitory activity towards fibril formation of β-amyloid peptide.
abstract: The standard extract of Ginkgo biloba leaves (EGb761) is used clinically in Europe for the symptomatic treatment of impaired cerebral function in primary degenerative dementia syndromes, and the results of numerous in vivo and in vitro studies have supported such clinical use. The abnormal production and aggregation of amyloid β peptide (Aβ) and the deposition of fibrils in the brain are regarded as key steps in the onset of Alzheimer's Disease (AD), and the inhibition of Aβ aggregation and destabilization of the preformed fibrils represent viable approaches for the prevention and treatment of AD. Flavonoid glycosides and terpene trilactones (TTLs) are the two main components of EGb761 which represent 24 and 6% of the overall content, respectively. In our research, seven abundant flavonoid glycosides 1-7 were isolated from the extract of Ginkgo biloba leaves and characterized by spectroscopic analysis. Furthermore, an ultra-high performance liquid chromatography method was established for the simultaneous quantification of these seven flavonoids. The inhibitory activities of these flavonoids, as well as four TTLs, i.e., ginkgolides A, B, and C and bilobalide (compounds 8-11), were evaluated towards Aβ42 fibril formation using a thioflavin T fluorescence assay. It was found that three flavonoids 1, 3 and 4 exhibited moderate inhibitory activities, whereas the other four flavonoids 2, 5, 6 and 7, as well as the four terpene trilactones, showed poor activity. This is the first report of the inhibition of Aβ fibril formation of two characteristic acylated flavonoid glycosides 6, 7 in Ginkgo leaves, on the basis of which the structure-activity relationship of these flavonoids 1-7 was discussed.
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xie
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong, China.
authors.forename: Jing-Rong
authors.initials: JR
authors.lastname: Wang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong, China.
authors.forename: Lee-Fong
authors.initials: LF
authors.lastname: Yau
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong, China.
authors.forename: Quan-Bin
authors.initials: QB
authors.lastname: Han
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong, China. zzzhao@hkbu.edu.hk.
authors.forename: Zhongzhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong, China. zhjiang@must.edu.mo.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Jiang
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry; D052160:Benzothiazoles; D005419:Flavonoids / Q000737:chemistry* / Q000302:isolation & purification; D020441:Ginkgo biloba / Q000737:chemistry*; D006027:Glycosides / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D007783:Lactones / Q000737:chemistry* / Q000302:isolation & purification; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry* / Q000302:isolation & purification; D013844:Thiazoles; D000096983:Ginkgo Extract
chemical_list: D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D005419:Flavonoids; D006027:Glycosides; D007783:Lactones; D010446:Peptide Fragments; D010936:Plant Extracts; D013729:Terpenes; D013844:Thiazoles; C075222:amyloid beta-protein (1-42); C518782:trilactone; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C009462:thioflavin T
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