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White matter lesion (WML) is caused by chronic cerebral hypoperfusion, which are usually associated with cognitive impairment. Evidence from recent studies has shown that ginkgolide B has a neuroprotective effect that could be beneficial for the treatment of ischemia; however, it is not clear whether ginkgolide B has a protective effect on WML. Our data show that ginkgolide B can promote the differentiation of oligodendrocyte precursor cell (OPC) into oligodendrocytes and promote oligodendrocyte survival following a WML. Ginkgolide B (5, 10, 20 mg/kg) or saline is administered intraperitoneally every day after WML. After 4 weeks, the data of Morris water maze suggested that rats’ memory and learning abilities were impaired, and the administration of ginkgolide B enhanced behavioral achievement. Also, treatment with ginkgolide B significantly attenuated this loss of myelin. Our result suggests that ginkgolide B promotes the differentiation of OPC into oligodendrocytes. We also found that ginkgolide B ameliorates oligodendrocytes apoptosis. Furthermore, ginkgolide B enhanced the expression of phosphorylated Akt and CREB. In conclusion, our data firstly show that ginkgolide B promotes oligodendrocyte genesis and oligodendrocyte myelin following a WML, possibly involving the Akt and CREB pathways.

Activation of NOD-like receptor protein 3 (NLRP3) inflammasome is implicated in the pathogenesis of neuropathic pain. Ginkgolide B contributes to the suppression of NLRP3 inflammasome activation to prevent hypoxic-ischemic brain injury. However, the role of ginkgolide B on neuropathic pain has not been reported yet. We have shown that administration of ginkgolide B lowered pain threshold measured by paw-withdrawal threshold and paw-withdrawal latency in rats subjected to chronic constriction injury. Nerve fibers in rats postchronic constriction injury were swollen, and the fibrous structure was disordered. Treatment with ginkgolide B attenuated the nerve fiber swelling and reduced the disordered fibrous structure. Ginkgolide B dosage dependently attenuated chronic constriction injury-induced increase of proinflammatory cytokines. Protein expression of NLRP3 and its downstream targets (caspase 1 and IL-1β) were increased by chronic constriction injury and reduced by ginkgolide B. Lastly, ginkgolide B counteracted with the promotive effects of chronic constriction injury on protein expression of TLR4 and p-NF-κB. In conclusion, ginkgolide B demonstrated anti-inflammatory and antinociceptive effects in rats' model with neuropathic pain by suppression of TLR4-NF-κB-mediated NLRP3 inflammasome activation.

Cerebrovascular and functional neurological lesions are the major disorders threatening human health and quality of life. The presence of the blood-brain barrier seriously affects the distribution and efficacy of various drugs in the brain. Ginkgolide B (GB) and Puerarin (Pue) are active pharmaceutical ingredients for the treatment of Parkinson’s disease. Here, we have developed a novel strategy to construct a GB-Pue niosomal composite drug. The in vitro cytology study of the niosomal composite drug showed that 20 mmol/L glutamate resulted in a mortality of 50–60% in the SHSY-5Y cells, while 30 μmol/L niosomal composite drug resulted in a survival rate of 95.2% in the SHSY-5Y cells with a maximum uptake value of 3.5 μg/mg and a peak uptake time at 2 hr. The monolayer cells reached a maximum transepithelial/endothelial electrical resistance (TEER) value of 626 Ω*cm2 at 36 hr in culture, and the cellular integrity was negatively correlated with the amount of drug accumulated in the cells. The accumulated GB and Pue in cells reached 86.53% and 76.49%, respectively. The 30 μmol/L composite drug preparation provided a higher cell survival rate in the glutamate (Glu) injured cells compared to the single drug preparations. Therefore, the composite preparation of the two drugs generated a synergistic effect, meeting the requirement for a combined use. The cell transmembrane transport experiments demonstrated that the pharmaceutical preparations traversed the blood-brain barrier through the active transport of cells.

Ginkgolide B (GB) and Puerarin (Pue) are active pharmaceutical ingredients for the treatment of Parkinson’s disease (PD); however, both are poorly water-soluble, which limits their bioavailability. The present study used the niosome vesicle encapsulation technique to prepare a novel GB composite drug. The conditions for GB–Pue niosomal complex preparation were as follows: a hydration temperature of 60°C, a hydrophilic–lipophilic balance of 10.5, a drug–carrier mass ratio of 8:100, and a surfactant–cholesterol mass ratio of 1.5:1. The niosomal complex suspension was uniformly distributed and milky white in color, with no stratification over a duration of 1 month. It had an average particle size of 187.3 nm, a particle-size distribution of 0.237, a GB encapsulation efficiency (EE) of 68.2%, a GB drug-loading rate of 90.1%, a Pue EE of 40.5%, and a Pue drug-loading rate of 83.3%. The optimal storage temperature for the niosomal complex suspension was 4°C. Following an intravenous injection of the niosomal complex suspension into the rat tail, the area under the curve (AUC) from 0 to 4 h was 54.1 h µg mL−1, with a mean residence time (MRT) of 0.96 h, a distribution half-life (T1/2α) of 0.195 h, and a total clearance of 0.003 L h−1 kg−1. The AUC and MRT of the composite prescription were 1.1- and 1.4-times those of the commercial injection, respectively, showing significantly increased sustained release and bioavailability. Moreover, the distribution of GB in the brain tissue was 1.8-times that of the commercial injection. In conclusion, the novel GB niosomal composite drug, with excellent stability, improved pharmacokinetics, and brain tissue distribution, demonstrates great potential for the delivery of GB and Pue for PD therapeutics.

Ginkgolide B exerts a cardioprotective function against ischemia-caused apoptosis in myocardial infarction. Here we sought out to address a functional mechanism associated with microRNA-29 (miR-29)...

Purpose: To determine the protective effect of ginkgolide B (GB) against isoproterenol (ISO)-induced chronic heart failure in a rat model. Methods: A total of 32 male Wistar rats were randomly divided into 4 groups. Rats in control group received only saline, while rats in GB alone group were injected with GB at a dose of 20 mg/kg body weight (bwt) intraperitoneally (i.p). Another group of rats was injected with ISO subcutaneously (s.c.) at a dose of 85 mg/kg for 2 days (ISO group). Rats in the GB+ISO group were administered GB at a dose of 20 mg/kg, i.p., for 7 days prior to exposure to ISO s.c. at a dose of 85 mg/kg. Results: Rats pre-treated with GB for 7 days prior to ISO exposure showed a significant decrease in cardiac infarct size, and marked decreases in the levels of cardiac biomarkers, inflammatory and apoptotic biomarkers, and lipid peroxidation (p < 0.05), but significant improvement in the levels ofendogenous antioxidants (p < 0.05). In addition, GB administration resulted in marked increases in the protein expression levels of heme oxygenase-1 (HO-1) and Nrf2 in cardiac tissue (p < 0.05). Conclusion: These results indicate that pre-treatment of chronic heart failure rats with GB for 7 consecutive days considerably lowered inflammatory and apoptotic markers via upregulation of Nrf2/HO-1 signaling pathway. Thus, GB has cardioprotective potential in humans. Keywords: Ginkgolide B, Nrf2/HO-1, Inflammatory markers, Apoptotic markers, Antioxidants

Cervical cancer is the fourth most common cancer among women worldwide. The treatment of cervical cancer mainly focused on surgery and radiotherapy, whereas the prognosis of invasive cervical cancer is still low. Ginkgo biloba is an ancient medicinal plant that has been used for decades to treat ischemic strokes and cognitive decline. Ginkgolide B, an active ingredient extracted from Ginkgo biloba, has multiple biological activities such as antioxidant, anti-apoptotic, and anti-inflammatory effects. Ginkgolide B has been found to have anti-tumor effects and inhibits the progression of multiple types of cancers. However, its potential role in cervical cancer is still unclear. In this study, we found that ginkgolide B suppresses the proliferation of cervical cancer cells in a dose-dependent manner. Ginkgolide B also induces cell cycle arrest and stimulates cell apoptosis by modulating the MAPK signaling pathway. We, therefore, present a novel and promising anti-tumor drug for the treatment of cervical cancer.

In this study, we introduce a method to formulate Ginkgolide B lipid microemulsion (GB-LM). We have assessed its general characteristics and pharmacokinetics in animals. Soybean oil (10.0%) and oleic acid (2.4%) were chosen as the oil phase, refined egg yolk lecithin (PC98T) (1.8%) as the surfactant, and glycerol (2.25%) as the co-surfactant. The optimized formulation process resulted in particles with average diameter of 185.9 ± 52.5 nm and the zeta potential of −19.8 ± 1.3 mV. The GB-LM remained steady for three months at room temperature. Giving each dose of 4 mg/kg to rats through the vein, a clearance rate of CL (L/h): 2.594 and C max (ng/mL) was achieved: 353.8 through pharmacokinetic analysis and statistical analysis. The AUC of GB-LM was about 1.57-fold higher than that of the products available in the market. In addition, brain tissue distribution studies show that after 0.5 h administration of GB, the concentration of GB in brain tissue can reach its maximum, and then significantly decrease after 2 hours. Therefore, the improved formulation of GB-LM shows encouraging results compared with present products in several features.

Despite numerous studies concerning the pathophysiology of migraine, the exact molecular mechanism of disturbances underlying migraine is still unknown. Furthermore, oxidative stress is considered to play a significant role in migraine pathogenesis. The notion of oxidative stress in migraine patients has been discussed for several decades. Over the past few years, among the substances that could potentially be used for migraine treatment, particular attention has been paid to the so-called nutraceutics, including antioxidants. Antioxidants supplied with food prevent oxidative stress by inhibiting initiation, propagation, and the oxidative chain reaction itself. Additionally, the agents used so far in the prevention of migraine indeed show some anti-oxidative action. The antioxidants discussed in the present paper are increasingly more often used by migraine patients not only due to mild or even a lack of side effects but also because of their effectiveness (decreased frequency of migraine episodes or shortening of an episode duration). The present review provides a summary of the studies on nutraceuticals with antioxidative properties.

Ginkgo biloba (a herbal product) has long been used in traditional Chinese medicine to treat cerebrovascular and cardiovascular diseases. Ginkgolide B is one of the important pharmacologically active components of Ginkgo biloba. Dimethylaminoethyl ginkgolide B (a novel ginkgolide B derivative) has been developed to overcome the poor water-solubility of natural drugs and to achieve higher bioavailability. This study investigated the potential effects of dimethylaminoethyl ginkgolide B on pregnant dams and embryo-fetal development in Sprague-Dawley rats and New Zealand white rabbits following maternal exposure on gestational day (GD) 6–15 and GD 6–18, respectively. Dimethylaminoethyl ginkgolide B was administered by intravenous injection to pregnant rats (0, 10, 30 and 100 mg kg(–1) d(–1)) and rabbits (0, 6, 18 and 60 mg kg(–1) d(–1)). Maternal toxicity signs, such as lower maternal body weight gain and food consumption, were observed at 100 mg kg(–1) d(–1) in rats and 60 mg kg(–1) d(–1) in rabbits. The developmental toxic effects included a decrease in fetal and placental weights, increased incidences of skeletal variations and delay in fetal ossification. Fetal growth and development were affected by dimethylaminoethyl ginkgolide B in the high-dose group in rabbits. The no-observed-adverse-effect level of dimethylaminoethyl ginkgolide B is considered to be 30 mg kg(–1) d(–1) for rats and 18 mg kg(–1) d(–1) for rabbits.

Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome-mediated chronic neuroinflammation plays a crucial role in the progression of Alzheimer's disease (AD), which is related to microglial activation. Using quantitative proteomic analysis, we identified 25 up-regulated and 83 down-regulated proteins in amyloid beta (Aβ)1-42-induced BV2 cells. Among the differentiallyexpressedproteins involved in inflammation, the NLRP3 protein level increased dramatically. Ginkgolide B (GB) prevents Aβ-induced neuroinflammation and neurotoxic effects in multiple neurodegenerative disorders. However, its role in NLRP3 inflammasome-mediated neuroinflammation in AD remain unknown. We found that GB treatment ameliorated Aβ1-42-induced pathological damages and inhibited NLRP3 inflammasome activation. Furthermore, GB enhanced the expression of M2 microglial markers and suppressed the expression of M1 microglial markers. Our findings suggest that GB treatment prevents the pathological processes of AD and suppresses neuroinflammation by inhibiting NLRP3 inflammasome activation and promoting microglial M2 polarization.

The blood–brain barrier permeability of ginkgolide B was examined using positron emission tomography (PET) probes of a 18 F-incorporated ginkgolide B ([ 18 F]- 2 ) and a 11 C-incorporated methylbenzyl-substituted ginkgolide B ([ 11 C]- 3 ). PET studies in monkeys showed low uptake of [ 18 F]- 2 into the brain, but small amounts of [ 11 C]- 3 were accumulated in the parenchyma. Furthermore, when cyclosporine A was preadministered to rats, the accumulation of [ 18 F]- 2 in the rat brain did not significantly change, however, the accumulation of [ 11 C]- 3 was five times higher than that in the control rat. These results provide effective approaches for investigating the drug potential of ginkgolides.

In this study, etherification of ginkgolide B and dimethylaminoethyl chloride hydrochloride was investigated as a model reaction in a micro-flow system (MFS), providing the resulting ethers in high yield with fewer side effects. Meanwhile, this novel process in MFS worked well for other ginkgolides from Ginkgol biloba and halides, giving moderate yields.

1. Ginkgolide B (GB), the most active of the ginkgolides, has been developed as a new drug for the treatment of vascular insufficiency; however, the pharmacokinetics of GB remain unclear. Here, we investigated the pharmacokinetics and urine excretion properties of GB in healthy Chinese subjects administered single- and multiple-dose injectable GB based on a new LC-MS/MS method. 2. GB pharmacokinetics were found to be dose-dependent from 20 to 60 mg. GB reached a steady state by day 6 with once-daily dosing at 40 mg. Systemic exposure to GB, as characterised by AUC0–∞, indicated accumulation following repeated once-daily dosing for seven consecutive days. The mean urinary cumulative excretion rate of GB in response to 20, 40, and 60 mg GB was 41.9 ± 18.5%, 32.9 ± 12.2%, and 43.9 ± 8.5%, respectively. 3. Dose-proportional pharmacokinetics of GB were observed after intravenous administration in healthy subjects. A gradual reduction in the volume of distribution and slight change in mean resistance time led us to conjecture the limited accumulation of GB based on distribution equilibrium in vivo. 4. This comprehensive study of the clinical pharmacokinetics of GB will provide useful information for its application and further development.

In this study, etherification process of ginkgolide B in a micro-flow system was investigated. With calcium carbonate as an acid-binding agent, the optimal result was obtained in such conditions: residence time 3 min, temperature 85 °C, molar ratio of ginkgolide B to dimethylamino ethyl chloride hydrochloride 1:2, molar ratio of ginkgolide B to potassium iodide 1:0.2, and molar ratio of ginkgolide B to calcium carbonate 1:2.5. Meanwhile, this novel process in MFS could proceed well for the etherification reaction between ginkgolide B and other halides, to afford the target products in moderate yields. Besides, salification reaction was conducted in a valve assisted micromixer by reacting dimethylaminoethyl ginkgolide B with methane sulfonic acid. Compared with conventional drugs, enhanced bioavailability was obtained when nano-scale drugs were dosed.

Ginkgolide B (GB) has been shown to exert neuroprotective effects against cerebral ischemia/reperfusion (I/R) injury. However, the underlying mechanism by which GB prevents ischemic cell death remains unclear. Lysosomal proteases, including cathepsins B and L, have been implicated in ischemic cell death following reperfusion. Therefore, in the present study, we investigated the role of GB with respect to cathepsin-mediated cell death following I/R. Both the expression and enzymatic activity of cathepsins B and L were significantly increased in the ischemic cortex following cerebral I/R injury. We found that GB treatment markedly decreased the activity and expression of cathepsins B and L following I/R. Moreover, GB reduced necrotic and apoptotic cell death following I/R. These data strongly suggest that GB prevents cathepsin-mediated cell death following focal cerebral I/R injury, and they might provide new insights into the mechanism of the neuroprotective effects of GB.

A liquid chromatography-mass spectrometry method was developed, validated, and applied to the pharmacokinetic study with doses of 0.68, 2.73 and 10.92 mg/kg of ginkgolide B in beagle dogs after intravenous infusion. An aliquot of blood samples were ­collected, separated and quantitatively analyzed by liquid chromatography-mass spectrometry method with mobile phase of acetonitrile-0.02% ammonia solution (33:67, v/v) at a flow rate of 0.8 mL/min on the UltimateTM XB-C18 column (5 μm, 4.6×150 mm). The method was sensitive, accurate and convenient, and can be used for the determination of ginkgolide B in beagle dogs. The Cmax and AUC0-∞ of GB increased with dose escalation, but ANOVA analyses showed that no significant difference was observed in other pharmacokinetic parameters between different doses. An LC/MS method was developed with good sensitivity, reproducibility and specificity. In the pharmacokinetic study of GB in beagle dogs, linear pharmacokinetics was found at doses from 0.62 to 10.92 mg/kg after a single-dose intravenous infusion. Gender differences were not observed in the pharmacokinetics of GB.

Objective This study describes the in vivo pharmacokinetics and metabolism of [14C]labeled XQ-1H in male rats. Methods XQ-1H is a methanesulfonate of XQ, 10-O-(N,N-dimethylaminoethyl)-ginkgolide B, a derivative of ginkgolide B (GB) with enhanced water solubility. Since it is very difficult to synthesize radiolabeled GB, the results obtained in this study may provide helpful insight to further ADME investigation of GB and its analogue compounds. After an i.v. administration of [14C]XQ-1H to male rats, XQ (the freebase form of XQ-1H) was extensively hydrolyzed, moderately metabolized, and mainly excreted in feces (71.5% of the dose) via the biliary route. Results The main enzyme mediated metabolic pathways were mono- and di-demthylation. Using the radiolabel form of XQ-1H, the temporal binding of XQ to red blood cells was observed. Conclusion Binding of XQ to RBCs may lower the blood's viscosity and thus provide symptomatic improvement of ischemic stroke patients.

The authors wish to correct the funding projects number of "Natural Science Foundation of Jiangsu Province" in the Acknowledgments section of this paper [1]: The correct funding projects number should be "No. BK20130403", not "No. BK2013403".[...].

Ginkgolide B (GB) has been demonstrated to have a variety of pharmacological actions. Accumulating evidence indicates that GB may exert a protective effect on brain injury. The study was designed to investigate the influence of GB on toll-like receptor 4 (TLR-4) and nuclear factor κB (NF-κB)-dependent inflammatory responses and neuronal cell apoptosis after traumatic brain injury (TBI). Wistar rats were subjected to 5, 10 and 20 mg/kg GB daily for 5 days, intraperitoneally, following TBI. Rats were sacrificed at hour 2, 6 and 12, as well as day 1, 2, 3 and 5 after TBI. The administration of 10 and 20 mg/kg GB could significantly (least-significant difference test: p 0.05). However, a clear concentration–response relationship was not found. Thus, GB may inhibit TLR-4 and NF-κB-dependent inflammatory responses, and furthermore lessen neuronal cell apoptosis after TBI, which may support the use of GB for the treatment of TBI. Copyright © 2012 John Wiley & Sons, Ltd.

This study was carried out to design and synthesize 10-O-nicotinate ginkgolide B (PGB) as a new prodrug of ginkgolide B (GB). The lipophilicity of PGB and GB was evaluated through the partition coefficient in 1-octanol–water system. The concentrations of PGB and GB in plasma and brain tissue were determined by liquid chromatography tandem mass spectrometry (LC–MS/MS) after intravenous administration of PGB or GB. After calculation and analysis, the drug-targeting index (DTI) of PGB was 7.45 and area under curve (AUC) value of GB decomposed from PGB was 2.45-fold higher than that of GB (parent drug) in brain. All the above results indicated that the brain targeting of GB was improved by prodrug strategy.

Summary 10-O-(N,N-dimethylaminoethyl)-ginkgolide B (XQ-1) is an intermediate for synthesizing 10-O-(N,N-dimethylaminoethyl)-ginkgolide B methanesulfonate (XQ-1H), which is a novel ginkgolide B derivative and is being developed as a platelet-activating factor antagonist. A specific and rapid liquid chromatographic method was developed for the quantitative analysis of XQ-1 and its three related impurities, which were 10-O-(N,N-dimethylaminoethyl)-11,12-seco-ginkgolide B (imp-1), 10-O-(N,N-dimethylaminoethyl)-11,12-seco-3,14-dehydroginkgolide B (imp-2) and 10-O-(N,N-dimethylaminoethyl)-3,14-dehydroginkgolide B (imp-3) simultaneously in XQ-1 samples. Chromatographic separation was achieved on a CN band stationary phase, with the mobile phase consisting of methanol and 20 mM dipotassium hydrogen phosphate (pH 7.5) (50:50, υ/υ) in isocratic elution. The flow rate was 1.0 mL min−1 and detector was set at 220 nm. The method was optimized by the analysis of the samples generated during the forced degradation studi...

The action of ginkgolide B (GB), a powerful compound of Ginkgo biloba extract, on glycine-mediated spontaneous currents in rat spinal sacral dorsal commissural nucleus (SDCN) neurons was examined. IPSCs evoked in spinal cord slices were inhibited in a dose-dependent manner by the addition of GB to the superfusion solution. The amplitude of eIPSCs was reduced to 61 ± 6.4% by 10 μM GB with acceleration of the kinetics of the currents, indicating the effect of GB on channel pores. Both the amplitude and success ratio (Rsuc) of eIPSC induced by electrical focal stimulation of single glycinergic nerve endings (boutons) also changed in the presence of 1 μM GB. These data suggest that GB modulates not only post-synaptic glycine receptors but also the pre-synaptic glycine release machinery.

In a multicentric, open, preliminary trial, we evaluated the use of ginkgolide B, a herbal constituent extract from Ginkgo biloba tree leaves, in the prophylactic treatment of migraine with aura (MA). Fifty women suffering from migraine with typical aura, or migraine aura without headache, diagnosed according to International Headache Society criteria, entered a six-month study. They underwent a two month run-in period free of prophylactic drugs, followed by a four month treatment period (subdivided into two bimesters, TI and TII) with a combination of 60 mg ginkgo biloba terpenes phytosome, 11 mg coenzyme Q 10, and 8.7 mg vitamin B2 (Migrasoll), administered twice daily. A detailed diary reporting neurological symptoms, duration, and frequency of MA was compiled by patients throughout the trial. The number of MA significantly decreased during treatment (from 3.7 +/- 2.2 in the run-in period, to 2.0 +/- 1.9 during TI and to 1.2 +/- 1.6 during TII; Anova for repeated measures: P < 0.0001). There was also a statistically significant decrease in the average MA duration, which was 40.4 +/- 19.4 min during run-in, 28.2 +/- 19.9 during TI, and 17.6 +/- 20.6 during TII. Total disappearance of MA was observed in 11.1% patients during TI and in 42.2% of patients during T2. No serious adverse event was provoked by Migrasoll administration. Ginkgolide B is effective in reducing MA frequency and duration. The effect is clearly evident in the first bimester of treatment and is further enhanced during the second.

A new compound decomposed from ginkgolide B(GB) is discovered and identified by MS and UV spectrum. It is the dehydrate of GB, which was named as ginkgolide K before. Differently, it cannot exist independently, but only in equilibrium with GB. It is found first time that 3-hydroxy is active in some solvent.

Objective To review the recent research progress in pharmacological actions and mechanisms of ginkgolide B. Data sources Information included in this article was identified by searching of PUBMED (1987 - 2006) online resources using the key terms "ginkgolide B", "platelet activating factor", and "pharmacological". Study selection Mainly original milestone articles and critical reviews written by major pioneer investigators of the field were selected. Results The key issues related to the pharmacological actions and mechanisms of ginkgolide B were summarized. The ginkgolide B possesses a number of beneficial effects such as anti-inflammatory, anti-allergic, antioxidant, and neuroprotective effects. Meantime, their mechaniams were discussed. Conclusions The Ginkgolide B is the most potent antagonist of platelet activating factor (PAF) and exhibits therapeutic action in a variety of diseases mainly by the PAF receptor.

In an attempt to increase productivity, the effects of the elicitors methyl jasmonate (MJ) and salicylic acid (SA) on the production of bilobalide (B), ginkgolide A (GA), and ginkgolide B (GB) were studied in cell suspension cultures of Ginkgo biloba. MJ treatments increased the amounts of B, GA, and GB, concomitant with a slight decrease in cell growth. After treatment of 0.01 mM MJ, levels of GA and GB increased 4.3- and 8.2-fold over controls by 12 h and declined after 24 h. The 1.0 mM MJ treatment produced a maximal release of B after 12 h of exposure and increased the concentration of B in the culture medium up to 6.25-fold compared with the controls. Treatment with 1.0 mM SA transiently enhanced GA and GB production up to 3.1- and 6.1-fold, respectively, compared with the control. However, treatment 1.0 mM SA did not have a significant effect on B production. When treated with 0.01 mM SA, the level of B in the cells was increased 5.4-fold over controls by 12 h and declined after 24 h. The concentrations and exposure times of both MJ and SA were factors that strongly affected the production of B, GA, and GB. The results from this study suggest that MJ and SA directly or indirectly increased the production of B, GA, and GB in cells, and stimulated the release of these metabolites into the culture medium.

Autosomal dominant polycystic kidney disease (ADPKD), a common disease with high incidence ratio, often causes great harm to people. However, no effective drug is currently available. The purpose o...

A quantum chemistry calculation at DFT-B3LYP/6-31G ∗ level on the geometry and IR spectrum of ginkgolide B was performed. The fully optimised geometry of ginkgolide B was found to be consistent with X-ray crystal structure. In addition, some important thermodynamic parameters were provided. The predicted vibrational bands of ginkgolide B scaled by a scaling factor of 0.945 were perfectly aligned to the experimental IR spectrum. Normal mode analysis on all 156 predicted bands showed that the stretching of O–H bonds of alcohol hydroxyl groups correspond to modes 156, 155 and 154 (from 3501 to 3443 cm −1 ). The stretching of C O bonds of carbonyl groups result in modes 132, 131 and 130 (from 1788 to 1764 cm −1 ). These assigned results were in accordance with what had been assigned in experiment based on IR spectroscopy. However, our normal mode analyses on the bands below 1192 cm −1 (mode 97) showed that none of these bands could be simply assigned to the stretching of a C–O bond. These bands are the results of coupling between the breathing of condensed ring structure and some other vibrations, such as the stretching of C–O bond or the rocking of C–H bond. Some of the bands that had been assigned to the stretching of C–O bond in experiment could be partly contributed by the vibration of C–O bonds. Furthermore, this study result showed that the stretching of C–H bond, and the rocking of t -Bu, methyl and methenyl groups can be located at the bands around 2900 and 1460 cm −1 , respectively.

Migraine is common in children, but few specific drugs are available. We performed an open-label comparison of effects of two nutraceutical preparations (ginkgolide B vs. Griffonia simplicifolia extract) on outcomes in 374 school-age children (mean 10.7 years) with migraine without aura. Half of them received ginkgolide B; and half, Griffonia simplicifolia. Both preparations were given orally twice a day for 6 months. Patients kept a headache diary. Outcomes at the beginning and end of treatment were compared. Both preparations reduced all outcome measures after 6 months of treatment. However, reductions in headache frequency, duration and intensity, PedMIDAS score and behavioural reactions to headache were significantly greater in the ginkgolide B group. Both nutraceutical treatments appear promising in paediatric migraine without aura, particularly because of their lack of side effects. However, the ginkgolide B preparation was significantly more effective in the medium-term (6 months).

The thermodynamic ionization constants (pK(a)(1), pK(a)(2), and pK(a)(3)) of ginkgolide B (9H-1,7a-(epoxymethano)-1H,6aH-cyclopenta[c]furo[2,3-b]furo-[3',2':3,4]cyclopenta[1,2-d]furan-5,9,12-(4H)-trione, 3-tert-butylhexahydro-4,7b,11-trihydroxy-8-methyl-) in aqueous solution have been settled by pH-metric and NMR studies. The three macroscopic pK(a) values as well as the water solubility and the water/n-octanol partition coefficient have been extracted from pH-metric data by means of a nonlinear regression methodology. NMR spectroscopy provided confirmation of the values of the macroscopic constants, information about the effective ionization pathways, and an estimation of the proportions of the various forms under physiologically relevant conditions.

Objective To study the pharmacokinetics and bioavailability of ginkgolides sustained-release tablet and conventional tablet in Beagle dogs. Method The concentrations of ginkgolides in plasma were determined by LC-MS. The main pharmacokinetic parameters of ginkgolides sustained-release tablet and conventional tablet in vivo were obtained using Pharmacokinetic software DAS 2.0. Result The C(max) of grinkgolide A in ginkgolide sustained-release tablet and conventional tablet were 443.51, 1 039.30 microg x L(-1), respecitvely. t(max) were 2.92, 1.08 h, respectively. AUC(0-12h) were 1 808.21, 2 041.37 h x microg(-1) x L(-1), respectively. MRT were 5.18, 3.18 h, respectively. The relative bioavailability of ginkgolides A was 88.58%. The C(max) of ginkgolide B in ginkgolide sustained-release tablet and conventional tablet were 407.13, 547.38 microg x L(-1), respectively. t(max) were 2.92, 1.08 h, respectively. AUC(01-12 h) were 1 987.31, 1 748.04 h x microg(-1) x L(-1), respectively. MRT were 6.05, 4.98 h, respectively. The relative bioavailability of ginkgolides B was 113.69%. Conclusion The ginkgolides sustained-release tablets have good sustained release characteristics and are bioequivalent to the reference formulation.

Objective To prepare ginkgolide B-loaded self microemulsifying drug delivery system (SMEDDS) and evaluate its quality. Method The solubility of ginkgolide B in different oil, surfactant and co-surfactant were measured by HPLC-ESI-MS. The GB-SMEDDS formulation was optimized by the self emulsifying efficiency of various combinations of oil and mix-surfactant evaluated by using pseudo-temary phase diagram. The preliminary stability of GB-SEMEDDS was evaluated by the variety of loading rate of GB and dispersed medium. The morphology, the particle size and the formulation stability were evaluated after diluting by 0.1 mol x L(-1) HCl. Result The blank self microemulsified system was composed of ethyl oleate-( cremophor EL-lecithin-ethanol, 4: 1:2) (40: 60), the loading dosage was 2.5%. Little influence of GB and emulsified medium was observed on the stability of GB-SEMDDS. After diluted with 0.1 mol x L(-1) HCl, the morphology of the microemulsion was homogeneous small spherical drops observed under electro-microscope. The particle size was (41.6 +/- 1.11) nm, the self microemulsifing time was around 2 min. The formulation was stable within 8 h, without significant changes in particle size and separation of drugs. Conclusion GB-SMEDDS is easy to prepare and its quality is stable. The solubility of GB was significantly improved by SMEDDS.

In this study, with flavonol glycosides (FG) and terpene lactones (TL) in ginkgo biloba extract (GBE) as the targets for separation, we investigated the effectiveness of molecular docking in adsorbent screening. Several polyamine-modified methyl acylate-co-divinylbenzene (MA-co-DVB) adsorbent models were built, and their affinity to rutin, quercetin and ginkgolide B (GB) was evaluated via molecular docking. The model of ethylenediamine-modified adsorbent showed the largest difference in affinity between to GB and to quercetin as well as rutin, and thus this adsorbent could have the best separation performance. The results of the subsequently conducted static adsorption and dynamic adsorption experiments correlated well with docking results. Finally, using ethylenediamine-modified MA-co-DVB adsorbent, nearly complete separation of the FG and TL in GBE was simply achieved by one step of adsorption-desorption. Thus, the reported molecular docking method is expected to be helpful for rapid adsorbent screening.

The effects of the extract of the leaves of Ginkgo biloba and of one of its major components, Ginkgolide B, on local cerebral glucose utilization (LCGU) have been studied in the awake adult rat. Ginkgolide B (10 mg/kg i.p.) had no significant effect on LCGU in 38 brain regions studied. In contrast, the Ginkgo biloba extract (150 mg/kg i.p. in 3 divided doses) produced significant and widespread decreases in LCGU in 21 brain regions (range 3–26% reduction). These results demonstrate that Ginkgo biloba is able to reduce brain glucose utilization, but that the substance responsible for this effect may not be Ginkgolide B.

To study the central role of ginkgolide B (BN52021) in regulating cardiovascular function of nerve center by examining the effects of ginkgolide B on the electrical activity of rat paraventricular nucleus (PVN) neurons in hypothalamic slice preparation and to elucidate the mechanism involved.Extracellular single-unit discharge recording technique.(1) In response to the application of ginkgolide B (0.1, 1, 10 micromol/L; n = 27) into the perfusate for 2 min, the spontaneous discharge rates (SDR) of 26 (26/27, 96.30%) neurons were significantly decreased in a dose-dependent manner. (2) Pretreatment with L-glutamate (L-Glu, 0.2 mmol/L) led to a marked increase in the SDR of all 8 (100%) neurons in an epileptiform pattern. The increased discharges were suppressed significantly after ginkgolide B (1 micromol/L) was applied into the perfusate for 2 min. (3) In 8 neurons, perfusion of the selective L-type calcium channel agonist, Bay K 8644 (0.1 micromol/L), induced a significant increase in the discharge rates of 8 (8/8, 100%) neurons, while ginkgolide B (1 micromol/L) applied into the perfusate, could inhibit the discharges of 8 (100%) neurons. (4) In 8 neurons, the broad potassium channels blocker, tetraethylammonium (TEA, 1 mmol/L) completely blocked the inhibitory effect of ginkgolide B (1 micromol/L).These results suggest that ginkgolide B can inhibit the electrical activity of paraventricular neurons. The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and potentially concerned with delayed rectifier potassium channel (K(DR)).

Four nitrogen-containing derivatives of ginkgolide B were synthesized to improve the physical–chemical properties and bioavailability of ginkgolide B. The reaction was accomplished with the nitrogen atom as neighboring group participating in the replacement reaction. All of the four compounds were proved to have excellent inhibiting effect on rabbit platelet aggregation induced by platelet-activating factor which is as well as ginkgolide B.

A method has been developed for measuring ginkgolide A, B, and bilobalide in ginkgo biloba L. extracts by using a self-assembled microdialysis device coupled on-line to high-performance liquid chromatography. The optimal conditions for dialysis efficiency and chromatographic analysis were investigated. The results show that the dialysis efficiencies for ginkgolide A, B, and bilobalide are 97.8-100.4%. For the spike concentration of 45 mg L(-1), the recoveries of ginkgolide A, B, and bilobalide in ginkgo biloba L. extracts were at 97-100.7% with 3.1-4.7% RSD. The proposed method has therefore been shown to be applicable to the analysis of ginkgolide A, B, and bilobalide in ginkgo biloba L. extracts.