3-methylquercetin and bilobalide

To estabish ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of quercetin(QCT), isorhamnetin(ISR), kaempferol(KMF), ginkgolide A(GA), ginkgolide B(GB), ginkgolide C(GC) and bilobalide(BB) in rat plasma and investigate the pharmacokinetic process of seven compounds after oral administration of Yindan Xinnaotong Ruanjiaonang, The results indicated that all calibrations curves showed good linearity (r≥0.997 1). RSD of intra-day and inter-day precisions were all within 11%. The matrix effects and extraction recovery were in the range of 93.28%-103.6% and 72.43%-95.77% respectively. The peak concentration (Cmax) of QCT, ISR, KMF, GA, GB, GC and BB were (45.02±11.28), (49.90±13.82), (27.85±8.38), (76.31±18.19), (76.54±15.43), (35.35±10.28), (48.70±12.34) μg•L⁻¹, respectively. The peak time (tmax) of seven constituents were (0.33±0.11), (0.50±0.23), (0.33±0.14), (0.75±0.29), (1.0±0.35), (1.5±0.23), (0.75±0.50) h, respectively. UPLC-MS/MS method established in this research was proved to be so rapid and sensitive that it can be applied to the pharmacokinetic study of seven bioactive constituents in Yindan Xinnaotong Ruanjiaonang.

Topics: Administration, Oral; Animals; Chromatography, High Pressure Liquid; Cyclopentanes; Drugs, Chinese Herbal; Furans; Ginkgolides; Kaempferols; Quercetin; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Tandem Mass Spectrometry

The aim of this study was to improve the dissolution rate and oral bioavailability of Ginkgo biloba extract (GBE) through the preparation of G. biloba extract solid dispersions (GBE-SD) via hot-melt extrusion (HME). First, we prepared the GBE-SD based on a Kollidon® VA64/Kolliphor® RH40 (85:15) spray dried powder. Then physicochemical properties were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR). The results indicated that GBE dispersed well in a carrier matrix. Subsequently, we studied the dissolution profile of total flavonoids (TFs) by HPLC-UV and total terpene lactones (TTLs) by HPLC-ELSD. The dissolution percentage of TFs and TTLs was improved within 120min. Finally, we studied the pharmacokinetic characteristics and bioavailability in rats by UPLC-MS/MS. The results showed that the Cmax and AUC0-t of bilobalide (BB), ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC), quercetin (QCT), kaempferol (KMF) and isorhamnetin (ISR) in rats were significantly increased after the oral administration of GBE-SD compared with results after the oral administration of GBE. These results suggest that the solid dispersion preparation by HME could serve as a promising formulation approach to enhancing the dissolution rate and oral bioavailability of GBE.

Topics: Animals; Biological Availability; Cyclopentanes; Furans; Ginkgo biloba; Ginkgolides; Kaempferols; Lactones; Male; Molecular Structure; Plant Extracts; Quercetin; Rats, Sprague-Dawley; Solubility

The complete and unambiguous (1)H NMR assignments of ten marker constituents of Ginkgo biloba are described. The comprehensive (1)H NMR profiles (fingerprints) of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, bilobalide, quercetin, kaempferol, isorhamnetin, isoquercetin, and rutin in DMSO-d(6) were obtained through the examination of 1D (1)H NMR and 2D (1)H,(1)H-COSY data, in combination with (1)H iterative full spin analysis (HiFSA). The computational analysis of discrete spin systems allowed a detailed characterization of all the (1)H NMR signals in terms of chemical shifts (δ(H)) and spin-spin coupling constants (J(HH)), regardless of signal overlap and higher order coupling effects. The capability of the HiFSA-generated (1)H fingerprints to reproduce experimental (1)H NMR spectra at different field strengths was also evaluated. As a result of this analysis, a revised set of (1)H NMR parameters for all ten phytoconstituents was assembled. Furthermore, precise (1)H NMR assignments of the sugar moieties of isoquercetin and rutin are reported for the first time.

Topics: Cyclopentanes; Furans; Ginkgo biloba; Ginkgolides; Kaempferols; Lactones; Magnetic Resonance Spectroscopy; Molecular Structure; Protons; Quercetin; Reference Standards; Rutin; Stereoisomerism

Codling moth, Cydia pomonella (L.), is a cosmopolitan pest of apple, potentially causing severe damage to the fruit. Currently used methods of combating this insect do not warrant full success or are harmful to the environment. The use of plant-derived semiochemicals for manipulation with fruit-infesting behavior is one of the new avenues for controlling this pest. Here, we explore the potential of Ginkgo biloba and its synthetic metabolites for preventing apple feeding and infestation by neonate larvae of C. pomonella. Experiments with crude extracts indicated that deterrent constituents of ginkgo are present among alkylphenols, terpene trilactones, and flavonol glycosides. Further experiments with ginkgo synthetic metabolites of medical importance, ginkgolic acids, kaempferol, quercetin, isorhamnetin, ginkgolides, and bilobalide, indicated that three out of these chemicals have feeding deterrent properties. Ginkgolic acid 15:0 prevented fruit infestation at concentrations as low as 1 mg/mL, bilobalide had deterrent effects at 0.1 mg/mL and higher concentrations, and ginkgolide B at 10 mg/mL. On the other hand, kaempferol and quercetin promoted fruit infestation by codling moth neonates. Ginkgolic acids 13:0, 15:1, and 17:1, isorhamnetin, and ginkgolides A and C had no effects on fruit infestation-related behavior. Our research is the first report showing that ginkgo constituents influence fruit infestation behavior and have potential applications in fruit protection.

Topics: Animals; Cyclopentanes; Fruit; Furans; Ginkgo biloba; Ginkgolides; Insecticides; Lactones; Larva; Malus; Moths; Plant Extracts; Salicylates

A reversed-phase high-performance liquid chromatography/electrospray ionisation mass spectrometry (RP-HPLC/ESI-MS) method was developed and validated for the simultaneous determination of ten major active components in Ginkgo biloba extract (bilobalide, ginkgolides A, B, C, quercetin, kaempferol, isorhamnetin, rutin hydrate, quercetin-3-beta-D-glucoside and quercitrin hydrate) which have not been previously reported to be quantified in a single analysis. The ten components exhibit baseline separation in 50 min by C18 chromatography using a water/1:1 (v/v) methanol/acetonitrile gradient. Quantitation was performed using negative ESI-MS in selected ion monitoring (SIM) mode. Good reproducibility and recovery were obtained by this method. The sensitivity of both UV and different mass spectrometry modes (full scan, selected ion monitoring (SIM), and selected reaction monitoring (SRM)) were compared and both quantitation with and without internal standard were evaluated. The analysis of Ginkgo biloba commercial products showed remarkable variations in the rutin and quercetin content as well as the terpene lactone contents although all the products satisfy the conventional quality control method.

Topics: Chromatography, High Pressure Liquid; Cyclopentanes; Dietary Supplements; Flavonols; Furans; Ginkgo biloba; Ginkgolides; Kaempferols; Plant Extracts; Quercetin; Rutin; Spectrometry, Mass, Electrospray Ionization

A comprehensive two-dimensional liquid chromatographic separation system based on the combination of an immobilized liposome chromatographic (ILC) column and an ODS column was developed for the separation of components in Ginkgo biloba, a traditional Chinese medicine. Two columns were coupled by a two-position, eight-port valve equipped with two storage loops, and the system was controlled by a computer. The effluent was detected both by a diode array detector and by an atmospheric pressure chemical ionization (APCI) mass spectrometer. Under the optimization separation conditions with the separation system, more than 41 components in the methanol extract of Ginkgo biloba were resolved. According to their UV and mass spectra, 13 of them were preliminarily identified as ginkgolide B, ginkgolide C, bilobalide, rutin, quercetin, quercetin-3-O-beta-D-glucosyl (1-2)-alpha-L-rhamnoside, quercetin-3-O-beta-D-glucoside, isorhamnetin, kaempferol-3-O-beta-D-glucosyl (1-2)-alpha-L-rhamnoside, isohamnetin-3-O-beta-D-rutinoside, kaempferol-3-O-beta-D-glucoside, kaempferol, kaempferol-3-O-beta-D-rutinoside.

Topics: Chromatography, High Pressure Liquid; Cyclopentanes; Drugs, Chinese Herbal; Flavonols; Furans; Ginkgo biloba; Ginkgolides; Kaempferols; Lactones; Medicine, Chinese Traditional; Monosaccharides; Quercetin; Rutin; Spectrometry, Mass, Electrospray Ionization