Study on network pharmacology of Ginkgo biloba extract against ischaemic stroke mechanism and establishment of UPLC-MS/MS methods for simultaneous determination of 19 main active components.

INTRODUCTION: Ginkgo biloba extract (GBE) is an effective substance from traditional Chinese medicine (TCM) G. biloba for treating ischaemic stroke (IS). However, its active ingredients and mechanism of action remain unclear. OBJECTIVES: This study aimed to reveal the potential active component group and possible anti-IS mechanism of GBE. MATERIALS AND METHODS: The network pharmacology method was used to reveal the possible anti-IS mechanism of these active ingredients in GBE. An ultra-high-performance liquid chromatography triple quadrupole electrospray tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous detection of the active ingredients of GBE. RESULTS: The active components of GBE anti-IS were screened by literature integration. Network pharmacology results showed that the anti-IS effect of GBE is achieved through key active components such as protocatechuic acid, bilobalide, ginkgolide A, and so on. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the possible anti-IS mechanism of GBE is regulating the PI3K-Akt signalling pathway and other signal pathways closely related to inflammatory response and apoptosis regulation combined with AKT1, MAPK, TNF, ALB, CASP3, and other protein targets. Nineteen main constituents in seven batches of GBE were successfully analysed using the established UPLC-MS/MS method, and the results showed that the content of protocatechuic acid, gallic acid, ginkgolide A, and so forth was relatively high, which was consistent with network pharmacology results, indicating that these ingredients may be the key active anti-IS ingredients of GBE. CONCLUSION: This study revealed the key active components and the anti-IS mechanism of GBE. It also provided a simple and sensitive method for the quality control of related preparations.

Ginkgo biloba extracts protect human retinal Müller glial cells from t-BHP induced oxidative damage by activating the AMPK-Nrf2-NQO-1 axis.

OBJECTIVES: Retinal Müller glial cell loss is almost involved in all retinal diseases, especially diabetic retinopathy (DR). Oxidative stress significantly contributes to the development of Müller glial cell loss. Ginkgo biloba extracts (GBE) have been reported to possess antioxidant property, beneficial in treating human retinal diseases. However, little is known about its role in Müller glial cells. This study investigated the protective effect of GBE (prepared from ginkgo biloba dropping pills) in human Müller glial cells against tert-butyl hydroperoxide (t-BHP)-induced oxidative stress and its underlying molecular mechanism. METHODS: MIO-M1 cells were pretreated with or without GBE prior to the exposure to t-BHP-induced oxidative stress. Cell viability, cell death profile and lipid peroxidation were subsequently assessed. Protein expression of the key anti-oxidative signalling factors were investigated. KEY FINDINGS: We showed that GBE can effectively protect human MIO-M1 cells from t-BHP-induced oxidative injury by improving cell viability, reducing intracellular ROS accumulation and suppressing lipid peroxidation, which effect is likely mediated through activating AMPK-Nrf2-NQO-1 antioxidant respondent axis. CONCLUSIONS: Our study is the first to reveal the great potentials of GBE in protecting human retinal Müller glial cell loss against oxidative stress. GBE might be used to prevent human retinal diseases particularly DR.

Ginkgo biloba extracts (GBE) protect human RPE cells from t-BHP-induced oxidative stress and necrosis by activating the Nrf2-mediated antioxidant defence.

OBJECTIVES: Age-related macular degeneration (AMD) is a prevalent ocular disease. Dry AMD accounts for most cases of blindness associated with AMD but there are no treatments. Oxidative stress-induced damage to retinal pigment epithelial (RPE) cells is a major contributor to the pathogenesis of dry AMD. This study investigated the protective actions of Ginkgo biloba extracts (GBE) in human RPE cells subjected to tert-butyl hydroperoxide (t-BHP)-mediated oxidative stress. METHODS: The human ARPE-19 cells were pre-treated with or without GBE before the exposure to t-BHP. Cell viability, cell death profile and lipid peroxidation were assessed. The findings were verified using human primary RPE cultures. KEY FINDINGS: GBE pre-treatment prevented the increase in lipid peroxidation and necrosis/ferroptosis, and the concurrent viability decrease in RPE cells exposed to t-BHP. It enabled the pronounced activation of Nrf2 and its downstream genes. We found that ERK1/2 phosphorylation was increased to a similar extent by t-BHP and GBE. CONCLUSION: This study revealed that GBE pre-treatment attenuates pro-oxidant stress and protects human RPE cells from oxidative injury by modulating ERK1/2-Nrf2 axis. These findings suggest that GBE has the potential to be developed as a agent that may be valuable in decreasing AMD progression.

Ginkgo biloba extracts inhibit post-ischemic LTP through attenuating EPSCs in rat hippocampus.

Ginkgo biloba extract 761 (EGb761), a standardized extract from the Ginkgo biloba leaf, is purported to inhibit NMDA receptor-mediated neuronal excitotoxicity and protect neurons form ischemic injury. However, the specific signal pathway involved in the effects of EGb761 on synaptic plasticity is still in dispute. In this article, effects of EGb761 and its monomer component ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC) and quercetin on rat hippocampal synaptic plasticity were studied. The evoked Excitatory postsynaptic currents (EPSCs) and miniature EPSCs were recorded on hippocampal slices from SD rats (14-21 days of age) by whole-cell patch-clamp recording and long-term potentiation (LTP) was induced by theta-burst stimulation. Acutely applied EGb761 inhibited the LTP, but bilaterally affect the evoked EPSCs. The evoked EPSCs were increased by incubation of lower concentration of EGb761, then the evoked EPSCs were decreased by incubation of higher concentration of EGb761. EGb761 monomer component GA, GB and GC could also inhibit the TBS-induced LTP and EPSC amplitude but not paired-pulse ratio (PPR). But quercetin, another monomer component of EGb761, led to increase in EPSC amplitude and decrease in PPR. Simultaneously, EGb761 and its monomer component ginkgolides inhibited the post-ischemic LTP (i-LTP) by inhibiting the EPSCs and the AMPA receptor subunit GluA1 expression on postsynaptic membrane. The results indicated that high concentration of EGb761 might inhibit LTP and i-LTP through inhibition effects of GA, GB and GC on AMPA receptors.

The characterisation of the in vitro metabolism and transport of 6-hydroxykynurenic acid, an important constituent of Ginkgo biloba extracts.

6-Hydroxykynurenic acid (6-HKA) is a nitrogen-containing phenolic acid compound in Ginkgo biloba leaves. The pharmacological activities of 6-HKA have been reported and shown that 6-HKA has the potential to become a therapeutic drug and may play an important role in the treatment of nervous system diseases. However, there are few studies on the drug metabolism and transport of 6-HKA. The aim of this study is to investigate the in vitro metabolism of 6-HKA and its interaction with multiple important drug transporters.The in vitro metabolism experiments in the present study demonstrate that 6-HKA might not undergo phase-I or phase-II metabolism in hepatic microsomes/S9 of rats. In addition, some drug transporters, including OAT1/3, OCT2, MDR1, OATP1B1, MATE1/2K and OCTN2, were investigated. The cellular uptake assays indicate that 6-HKA exhibits inhibition to the transport of classical substrates mediated by OAT3, OCT2, MATE2K and OCTN2 but has no significant effect on the transport of substrates mediated by MDR1, OAT1, OATP1B1 or MATE1. Further investigation of cellular accumulation assays shows that 6-HKA might be the substrate of OAT3, but not OCT2 or OCTN2. The bidirectional transport study suggests that 6-HKA is not a substrate of MDR1.The information about the in vitro metabolism of 6-HKA and the interaction between 6-HKA and some transporters will help us to better understand the pharmacokinetic properties of 6-HKA and provide reference for its pharmacodynamics, DDIs and drug-food interactions studies.

Effects of ginkgo biloba extract on learning and memory and protection of hippocampal neurons in rats with vascular dementia / 中华行为医学与脑科学杂志

Objective To investigate the effects of ginkgo biloba extracts ( EGb761) on learning and memory and the protective effect on hippocampal neurons in rats with vascular dementia (VD). Meth-ods Ninety rats were randomly divided into sham-operated group,model group and EGb761-treated group, with 30 rats in each group. Rats in each group were examined at 15 days,1 month and 2 months,with 10 rats in each time point. VD model was established by bilateral carotid artery occlusion combinding with injection of sodium nitroprusside. Morris water maze test was used to detect the learning and memory function of rats. The expression of glial fibrillary acidic protein (GFAP) was observed by immunofluorescence. Western-blot was used to detect the protein expression of P-glycoprotein ( P-GP ), excitatory amino acid transporters 2 ( EAAT2),caspase-3 and cleaved caspase-3. RT-PCR was used to detect the mRNA expression of P-GP and EAAT2 in the hippocampus of rats in each group. Results Compared with sham-operated group,the escape latency (EL) was significantly prolonged at each time point in model group ( sham-operated group:15 days (15. 52±3. 23) s,1 month ( 14. 21 ± 2. 62) s,2 months ( 15. 37 ± 1. 66) s;model group:15 days ( 30. 35 ± 2. 30)s,1 month(40. 78± 3. 55) s, 2 months( 33. 88± 1. 47) s; all P<0. 01). The EL of EGb761-treated group was significantly shorter than that of the model group(EGb761-treated group:15 days(25. 69±2. 44)s, 1 month(20. 78±1. 72)s,2 months(18. 23±1. 67)s,all P<0. 01). Immunofluorescence showed that the ex-pression of GFAP in EGb761-treated group was lower than that of the model group (P<0. 01). Western blot showed that cleaved caspase-3 protein expression in EGb761-treated group at each time point was significant-ly lower than that in the model group (P<0. 01). Western-blot and RT-PCR results showed that the protein and mRNA expression of P-GP and EAAT2 in EGb761-treated group at 15 day and 1 month time points were significant increased than those in the model group (P<0. 01). At 2 month time point,which were lower than those in the model group (P<0. 01). Conclusion EGb761 can improve the learning and memory ability of VD rats,and regulate the protein and mRNA expression of P-GP and EAAT2 in hippocampus of VD rats at different time points (up-regulated in 1 month and down-regulated in 2 month),and down-regulate the ex-pression of cleaved caspase-3 and GFAP at different time points,thereby delaying the brain damage of VD rats and protecting neurons.

Ginkgo biloba extracts prevent aortic rupture in angiotensin II-infused hypercholesterolemic mice.

Abdominal aortic aneurysms (AAAs) are a chronic vascular disease characterized by pathological luminal dilation. Aortic rupture is the fatal consequence of AAAs. Ginkgo biloba extracts (GBEs), a natural herb extract widely used as food supplements, drugs, and cosmetics, has been reported to suppress development of calcium chloride-induced AAAs in mice. Calcium chloride-induced AAAs do not rupture, while angiotensin II (AngII)-induced AAAs in mice have high rate of aortic rupture, implicating potentially different mechanisms from calcium chloride-induced AAAs. This study aimed to determine whether GBE would improve aortic dilation and rupture rate of AngII-induced AAAs. Male apolipoprotein E (apoE) -/- mice were infused with AngII and administered either GBE or its major active ingredients, flavonoids and ginkgolides, individually or in combination. To determine the effects of GBE in mice with established AAAs, male apoE-/- mice were firstly infused with AngII for 28 days to develop AAAs, and then administered either GBE or vehicle in mice with established AAAs, which were continuously infused with AngII for another 56 days. GBE, but not the two major active components separately or synergistically, prevented aortic rupture, but not aortic dilation. The protection of GBE from aortic rupture was independent of systolic blood pressure, lipid, and inflammation. GBE also did not attenuate either aortic rupture or progressive aortic dilation in mice with established AAAs. GBE did not reduce the atherosclerotic lesion areas, either. In conclusion, GBE prevents aortic rupture in AngII-infused hypercholesterolemic mice, but only in the early phase of the disease development.

Ginkgo biloba extract 761 enhances 5-fluorouracil chemosensitivity in colorectal cancer cells through regulation of high mobility group-box 3 expression.

Although the standard ginkgo biloba extract EGb 761 exhibits antioxidative, anti-apoptotic, and anticancer properties, there is no research focusing on the chemopreventive effects of EGb 761 in colorectal cancer (CRC). The present study investigated whether EGb 761 could increase 5-fluorouracil (5FU) sensitivity in CRC and its potential mechanism. We found that combined EGb 761 and 5FU treatment significantly elevated the chemosensitivity of CRC cells to 5FU in 5FU-resistant (5FUR) CRC cells, whereas no obvious cytotoxicity of EGb 761 was observed in parental cells. Then, real-time PCR and western blotting revealed that EGb 761 notably attenuated drug resistance through inhibition of epithelial-mesenchymal transition (EMT) factors (increased E-cadherin and decreased vimentin). In addition, we found that EGb 761 significantly inhibited 5FU-induced upregulation of high mobility group-box 3 (HMGB3) expression in 5FUR CRC cells both at mRNA and protein levels. Knockdown of HMGB3 effectively reversed 5FU-induced EMT and attenuated 5FU-induced cytotoxicity in 5FUR CRC cells while overexpression of HMGB3 achieved the opposite results. Moreover, we found that knockdown of HMGB3 effectively reversed the EGb 761-induced inhibition of the Wnt/ß-catenin pathway. The results of the current study collectively demonstrated that EGb 761 can chemosensitize 5FUR CRC cells by inhibiting an EMT phenotype via regulation of HMGB3 expression, suggesting it to be a novel chemoprotective agent in CRC.

Improving antioxidant and antiproliferative activities of colla corii asini hydrolysates using ginkgo biloba extracts.

Colla corii asini hydrolysates (ACCH) and ginkgo biloba extracts (EGb) possess more potent antioxidant effects when used in combination than when used alone. The mixture of ACCH and EGb at a dose ratio of 20:4(w:w) showed the highest radical scavenging activity with IC 50 of 0.17 ± 0.01, 0.43 ± 0.02 and 1.52 ± 0.07 mg/ml against DPPH, ABTS and HO · free radicals, respectively. Furthermore, the inhibition of breast cancer cells MCF-7 and MDA-MB-231 proliferation increased when these cell lines were treated with a combination of ACCH and EGb for 72 hr, with IC 50 of 4.32 ± 0.12 mg/ml and 0.39 ± 0.01 mg/ml, respectively. The findings indicated that the mixtures of ACCH and EGb could be used to prevent and treat some diseases caused by the excessive free radicals, especially cancer. Therefore, the mixtures of ACCH and EGb might serve as a natural source of desirable antioxidant and anticancer agents for the nutraceutical and pharmaceutical industries.

Ginkgo biloba extracts-loaded starch nano-spheres: Preparation, characterization, and in vitro release kinetics.

Ginkgo as a promising edible material and herbal medicine has received much attention due to its abundant starch contents and functional ingredient ginkgo biloba extracts (GBEs). Many foreign scholars suggest that GBEs can effectively ameliorate the symptoms of mild memory impairment and Alzheimer's dementia. However, an insurmountable problem with application of the GBEs is its low bioavailability, which restricts its application in vivo. Considering the biocompatibility between GBEs and starch, we have prepared ginkgo and corn starch-based nano-carriers, and thereby loaded GBEs onto starch nano-spheres (SNPs) by nanoprecipitation. Compared with unloaded SNPs (201-250nm), the mean sizes of the monodispersed and spherical GBEs-loaded SNPs were 255-396nm. Moreover, the loading amounts of GBEs onto ginkgo, and corn SNPs were 0.661-1.045, and 0.560mg/mg, respectively. In addition, in artificial gastric and intestinal juices, the GBEs-loaded SNPs exhibited a better sustained release than free GBEs.

Synergistic effects and related bioactive mechanism of Potentilla fruticosa L. leaves combined with Ginkgo biloba extracts studied with microbial test system (MTS).

BACKGROUND: Potentilla fruticosa, also called "Jinlaomei" and "Gesanghua", is widely used as folk herbs in traditional Tibetan medicine in China to treat inflammations, wounds, certain forms of cancer, diarrhoea, diabetes and other ailments. Previous research found P. fruticosa leaf extract (C-3) combined with Ginkgo biloba extracts (EGb) showed obvious synergistic effects in a variety of oxidation systems. The aim of the present study was to further confirm the synergy of P. fruticosa combined with EGb viewed from physiological bioavailability and explore the related bioactive mechanism behind the synergism. METHODS: The microbial test system (MTS) was adopted to evaluate the related bioactive mechanism. The synergistic effects were evaluated by isobolographic analysis. The H2O2 production rate and antioxidant enzyme (Catalase (CAT), Peroxidase (POD), Superoxide dismutase (SOD), Glutathione peroxidase (GSH-PX)) activities were determined by the colorimetric method. Enzyme gene (CAT, SOD) expression was measured by real time-PCR. RESULTS: The MTS antioxidant activity results showed the combination of C-3 + EGb exhibited synergistic effects especially at the ratio 5:1. Components of isorhamnetin and caffeic acid in C-3 and EGb displayed strong antioxidant activities on MTS and their combination also showed significant synergy in promoting H2O2 production. The combinations of C-3 + EGb and isorhamnetin + caffeic acid promoted CAT and SOD enzyme activities and the ratio 1:1 exhibited the strongest synergy while no obvious promotion on POD and GSH-PX enzyme activities was found. Both combinations above promoted gene expression of CAT and SOD enzymes and the ratio 1:1 exhibited the strongest synergy. CONCLUSIONS: Antioxidant activity results in MTS further confirmed the significant synergy of C-3 combined with EGb and isorhamnetin combined with caffeic acid. The synergy of C-3 combined with EGb may be attributed to the combination of isorhamnetin + caffeic acid, which promoted CAT and SOD enzyme gene expression and further promoted the enzyme activities in E. coli. This study could further provide rational basis for optimizing the physiological bioavailability of P. fruticosa by using natural and safe antioxidants in low doses to produce new medicines and functional products.

An Overview of Systematic Reviews of Ginkgo biloba Extracts for Mild Cognitive Impairment and Dementia.

Ginkgo biloba extracts (GBEs) have been recommended to improve cognitive function and to prevent cognitive decline, but earlier evidence was inconclusive. Here, we evaluated all systematic reviews of GBEs for prevention of cognitive decline, and intervention of mild cognitive impairment (MCI) and dementia. Six databases from their inception to September 2015 were searched. Ten systematic reviews were identified, including reviews about Alzheimer's disease (n = 3), about vascular dementia (n = 1), about both Alzheimer's disease and vascular dementia (n = 2), about Alzheimer's disease, vascular dementia and mixed dementia (n = 3), and a review about MCI (n = 1). Based on the overview quality assessment questionnaire, eight studies were scored with at least 5 points, while the other two scored 4 points and 3 points, respectively. Medication with GBEs showed improvement in cognition, neuropsychiatric symptoms, and daily activities, and the effect was dose-dependent. Efficacy was convincingly demonstrated only when high daily dose (240 mg) was applied. Compared with placebo, overall adverse events and serious adverse events were at the same level as placebo, with less adverse events in favor of GBE in the subgroup of Alzheimer's disease patients, and fewer incidences in vertigo, tinnitus, angina pectoris, and headache. In conclusion, there is clear evidence to support the efficacy of GBEs for MCI and dementia, whereas the question on efficacy to prevent cognitive decline is still open. In addition, GBEs seem to be generally safe.

The effects of the standardized extracts of Ginkgo biloba on steroidogenesis pathways and aromatase activity in H295R human adrenocortical carcinoma cells.

OBJECTIVES: Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. METHODS: Cortisol, aldosterone, testosterone, and 17ß-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/ 17/19/21) and the hydroxysteroid dehydrogenases (3ß-HSD2 and 17ß-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. RESULTS: H295R cells exposed to EGb761 (10 and 100 µg/mL) showed a significant decrease in 17ß-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and 17ß-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/ Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. CONCLUSIONS: These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and 17ß-HSD1, and lead to a decrease in 17ß-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

The effects of the standardized extracts of Ginkgo biloba on steroidogenesis pathways and aromatase activity in H295R human adrenocortical carcinoma cells

OBJECTIVES: Aromatase inhibitors that block estrogen synthesis are a proven first-line hormonal therapy for postmenopausal breast cancer. Although it is known that standardized extract of Ginkgo biloba (EGb761) induces anti-carcinogenic effects like the aromatase inhibitors, the effects of EGb761 on steroidogenesis have not been studied yet. Therefore, the effects of EGb761 on steroidogenesis and aromatase activity was studied using a H295R cell model, which was a good in vitro model to predict effects on human adrenal steroidogenesis. METHODS: Cortisol, aldosterone, testosterone, and 17β-estradiol were evaluated in the H295R cells by competitive enzyme-linked immunospecific assay after exposure to EGb761. Real-time polymerase chain reaction were performed to evaluate effects on critical genes in steroid hormone production, specifically cytochrome P450 (CYP11/17/19/21) and the hydroxysteroid dehydrogenases (3β-HSD2 and 17β-HSD1/4). Finally, aromatase activities were measured with a tritiated water-release assay and by western blotting analysis. RESULTS: H295R cells exposed to EGb761 (10 and 100 μg/mL) showed a significant decrease in 17β-estradiol and testosterone, but no change in aldosterone or cortisol. Genes (CYP19 and 17β-HSD1) related to the estrogen steroidogenesis were significantly decreased by EGb761. EGb761 treatment of H295R cells resulted in a significant decrease of aromatase activity as measured by the direct and indirect assays. The coding sequence/ Exon PII of CYP19 gene transcript and protein level of CYP19 were significantly decreased by EGb761. CONCLUSIONS: These results suggest that EGb761 could regulate steroidogenesis-related genes such as CYP19 and 17β-HSD1, and lead to a decrease in 17β-estradiol and testosterone. The present study provides good information on potential therapeutic effects of EGb761 on estrogen dependent breast cancer.

The effect of Ginkgo biloba extracts on the pharmacokinetics and pharmacodynamics of cilostazol and its active metabolites in healthy Korean subjects.

AIMS: The primary objective of this study was to evaluate the effects of Ginkgo biloba extracts (GBE) on the pharmacokinetics of cilostazol and its metabolites. The secondary objective was to assess the effect of GBE on the pharmacodynamics of cilostazol. METHODS: A randomized, double-blind, two-way crossover study was conducted with 34 healthy Korean subjects. All subjects were given an oral dose of cilostazol (100 mg) plus GBE (80 mg) or cilostazol (100 mg) plus placebo twice daily for 7 days. Plasma concentrations of cilostazol and its active metabolites (3,4-dehydrocilostazol and 4'-trans-hydroxycilostazol) were measured using liquid chromatography-tandem mass spectroscopy on day 7 for pharmacokinetic assessment. The adenosine diphosphate-induced platelet aggregation and bleeding time were measured at baseline and on day 7 for pharmacodynamic assessment. RESULTS: The geometric mean ratios of area under the concentration-time curve for dosing interval for cilostazol plus GBE vs. cilostazol plus placebo were 0.96 (90% confidence interval, 0.89-1.03; P = 0.20) for cilostazol, 0.96 (90% confidence interval, 0.90-1.02; P = 0.30) for 3,4-dehydrocilostazol and 0.98 (90% confidence interval, 0.93-1.03; P = 0.47) for 4'-trans-hydroxycilostazol. The change of aggregation after administration of cilostazol plus GBE seemed to be 1.31 times higher compared with cilostazol plus placebo, without statistical significance (P = 0.20). There were no significant changes in bleeding times and adverse drug reactions between the treatments. CONCLUSIONS: Co-administration of GBE showed no statistically significant effects on the pharmacokinetics of cilostazol in healthy subjects. A large cohort study with long-term follow-up may be needed to evaluate the possible pharmacodynamic interaction between cilostazol and GBE, given that there was a remarkable, but not statistically significant, increase in inhibition of platelet aggregation.

Development in New Dosage Forms of Active Components from Ginkgo Biloba Extracts / 中国药师

The main active components in Ginkgo biloba extracts were Ginkgo biloba flavonoids and lactone compounds. This pa-per reviewed on the kinds and pharmacological effects of the active ingredients in Ginkgo biloba extracts, and focused on four aspects including controlled-release preparations, solubilized solid preparations, nanoparticle formulations and time- and site-specific formula-tions to introduce the development in the new dosage forms of Ginkgo biloba flavonoids and lactone compounds.

Technology Optimization and Identification of Ginkgo Biloba Extracts-hydroxyprop-?-cyclodextrin(GBE-HP-?-CD) Inclusion Compounds / 中国药房

OBJECTIVE:To optimize the preparation technology of Ginkgo biloba extracts-hydroxyprop-?-cyclodextrin(GBE-HP-?-CD) inclusion compounds and to identify this inclusion compound.METHODS:The optimum preparation condition was studied by orthogonal test with encapsulation rate as the index of evaluation.The inclusion compounds were prepared with solution-agitating technique.The inclusion compounds were identified by phase solubility diagra-m,differential scanning calorimetry(DSC) and infrared spectroscopy methods,respectively.RESULTS:The optimum inclusion condition was as follows:the ratio of GBE to HP-?-CD=1.5∶1;agitating time=6 h;inclusion temperature=50 ℃.CONCLUSION:It has been preliminarily proved that it is possible for Ginkgo biloba extracts and hydroxyprop-?-cyclodextrin to be made into inclusion compounds.HP-?-CD has satisfactory solublization on Ginkgo biloba extracts.