CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Tingbiao Wu,Deyao Li,Qiuyu Chen,Dezhi Kong,Hongxuan Zhu,Hefeng Zhou,Qingwen Zhang,Guozhen Cui
Ginkgolide B (GB), a compound derived from Ginkgo biloba , exhibits significant cardioprotective properties, although its precise molecular target has yet to be identified. In this study, we synthesized a biotin-labeled GB probe (GB-biotin) to identify the molecular targets of GB. Our experiments demonstrated that treatment with GB or GB-biotin reduced mitochondrial injury, restored mitochondrial membrane potential, and decreased cell apoptosis in a concentration-dependent manner. Additionally, GB increased mitochondrial oxygen consumption rate, indicating improved mitochondrial bioenergetics. Proteomic analysis revealed that the voltage-dependent anion channel 1 (VDAC1) is a key protein that interacts with GB-biotin. This finding was further confirmed through cellular thermal shift assay (CETSA) and molecular docking, which revealed hydrogen bond formation between GB and VDAC1. Furthermore, overexpression of VDAC1 diminished the protective effects of GB, highlighting the crucial role of VDAC1 in GB-mediated cardioprotection. These findings identify VDAC1 as a therapeutic target for GB in vitro , providing valuable insights into the cardioprotective mechanisms of GB and the development of novel cardioprotective strategies.
研究领域:
药理学
·
分子生物学
·
心血管科学
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DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 2
·e6070
·
IF 1.7
Li Li,Dan Yu,Wen-Fei Sun,Qi-Zhong Jin,Xing-Jie Chang,Qian Shi
Ginkgolide B (GB) is the main active ginkgolide in Ginkgo biloba leaves extract. Pharmacological study suggested that GB exhibits protective effect on nervous system impaired and can be used in the treatment of dementia, cerebral insufficiency or related cognitive decline. However, the information on pharmacokinetics of GB in vivo was limited. In this study, a sensitive LC–MS/MS analytical method was developed to accurately determinate the concentration of GB in dog plasma and applied to the pharmacokinetic study of GB in dogs after bolus injection of GB. A portion of 100 μL dog plasma was pretreated by liquid–liquid extraction using 1 mL of ethyl acetate. The GB and IS were separated on a Waters ACQUITY HSS T3 column using acetonitrile and water containing 0.1% formic acid as mobile phase, at a flow rate of 0.4 mL/min. Multiple-reaction monitoring (MRM) mode was used for quantitative analysis of GB and tolbutamide (internal standard) in negative electrospray ionization. GB showed excellent linearity with correlation coefficient > 0.99 over the concentration range of 1–5000 ng/mL. The intra and interday RSD% were less than 7.4%, while the RE% ranged from −6.1% to 9.6%. The mean extraction recovery was > 83.1%. The validated method was further successfully applied to pharmacokinetic study of GB in dog plasma. Dose-proportional pharmacokinetics of GB were observed after bolus injection administration in dogs. This comprehensive study of the pharmacokinetics of GB in dogs will provide useful information for its further development in clinic.
研究领域:
药理学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2020
·Vol. 25
·期 17
·3976
·
IF 3.267
Tingting Wu,Xianying Fang,Jiahui Xu,Yan Jiang,Fuliang Cao,Linguo Zhao
Ginkgo biloba extract (EGB) has many pharmacological activities. In the quality standard of EGB, the main quality control indexes are total flavone (content ≥ 24%) and total lactone (content ≥ 6%). There are no specific limits for nearly 70% of “other components”. In recent years, in order to pursue the production of a high-ketone ester, some enterprises removed the unwanted components, including some organic acids. Protocatechuic acid (PCA), as an important organic acid, has been reported to have a variety of biological activities. It is necessary to explore whether it can promote the biological activities of the main functional components of EGB. In this study, PCA was selected to be combined with Ginkgolide B (GB) for the treatment of Parkinson’s disease. In vitro, rotenone (rot) was used to induce PC12 cells. The survival rate was tested by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dimethyltetrazolium bromide (MTT) assay. Reactive oxygen species (ROS) and antioxidase were detected to analyze the effects of drugs on oxidative stress. The apoptosis was tested via Western blot. The results show that the cell viability was increased, morphology was improved, the oxidative stress level decreased, and the apoptosis was inhibited after the combination treatment of GB and PCA, and the effect was better than GB or PCA alone. In vivo, MPTP (30 mg/kg) was used to induce Parkinson’s disease (PD) in male C57BL/6 mice. The motor ability of the mice was measured by pole-climbing and the suspension. The injury of nerve cells was indicated by HE staining. Oxidative stress levels were tested via antioxidant enzyme activity. The number of dopaminergic neurons was reflected by TH staining. Results show that the combination treatment of GB and PCA could significantly restore the motor ability of PD mice, reduce the injury of nerve cells, improve the activity of the antioxidant enzyme in the brain tissue, and increase the expression of TH in the substantia nigra of midbrain. Our study shows that PCA increases the efficacy of GB (the main functional ingredient of EGB) in the treatment of Parkinson’s disease, which provides a new idea for the treatment of nervous system diseases and a new concept for the efficient utilization of active components inGinkgo bilobaleaves.Keywords:Ginkgolide B;protocatechuic acid;synergistic effect;Parkinson’s disease
研究领域:
药理学
·
神经科学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 37
·31101-31106
·
IF 3.289
Ailing Hui,Shijing Zhu,Huayang Yin,Li Yang,Zheng Zhang,An Zhou,Jian Pan,Wencheng Zhang
A series of ginkgolide B derivatives (GBD) were designed for delivery of ginkgolide B (GB) across the blood–brain barrier to the brain. Three GBD had shown considerable brain-targeting ability in our previous study. Among them, the ginkgolide B pyrazine (PGB) derivative was selected as a promising novel GB derivative because of its highest brain distribution. Further investigations with regard to PGB and GB's effects on inhibiting the expression of P-gp and attenuating the efflux function of P-gp were reported in this study. They were considered a big step towards better understanding the relationship between GBD's brain-targeting behavior and P-gp regulation. Western blot analysis indicated that PGB was more effective in inhibiting the expression of P-gp than GB in rat brain microvessel endothelial cells (rBMECs) and rat cerebral cortexes and hippocampus. Moreover, the efflux function of P-gp via the transportation of rhodamine 123 was significantly inhibited in PGB-treated rat brains. Preventive medication with PGB induced a better protection of the integrity of the BBB in incomplete ischemia mice. Our findings revealed that an attenuated expression level and efflux function of P-gp and improved protective effect could be realized by the ginkgolide B derivative. These investigations will pave the way for designing more efficient brain-targeting derivatives of ginkgolide and some other central nervous system drugs.
研究领域:
药理学
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神经科学
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产品关联
DOI
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2019
·Vol. 43
·期 2
·514-523
·
IF 2.516
Honghong Li,Wencheng Zhang,Zeyu Wu,Xusheng Huang,Ailing Hui,Yiwen He,Haiyan Wang
Ginkgolide B is in great demand worldwide on account of its extensive and excellent pharmacological effects, however, it is difficult to separate and purify ginkgolide B. In this study, ginkgolide B molecularly imprinted polymers were prepared by combining software simulation and molecular imprinting technique, and its characterization and adsorption performed evaluation were performed to understand the adsorption behavior of the polymers. The adsorption equilibrium concentration of molecularly imprinted polymers was 0.70 mg/mL, and the adsorption equilibrium time was 4 h. Meanwhile, the adsorption isotherm of the polymers for ginkgolide B fitted well with the Langmuir model, and the adsorption kinetics was in line with the pseudo-second-order kinetics. In contrast, the adsorption capacity of molecularly imprinted polymers on ginkgolide B was higher than that of non-molecular imprinted polymers, with better selectivity and better adsorption after repeated use for six times. The application experiments showed that molecular imprinted polymers have a good adsorption effect in low purity samples. Therefore, the polymers reported herein can be expected to apply in the adsorption and separation of ginkgolide B samples.
研究领域:
药学
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生物化学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2015
·Vol. 20
·期 11
·20031-20041
·
IF 2.416
Jie Zhao,Ting Geng,Qi Wang,Haihong Si,Xiaoping Sun,Qingming Guo,Yanjing Li,Wenzhe Huang,Gang Ding,Wei Xiao
Ginkgolide B (GB), an important active constituent ofGinkgo bilobaextract, has been used in clinical applications for the treatment of dementia, cerebral insufficiency or related cognitive decline. To investigate the main pharmacokinetic characteristics of three different GB formulations in beagle dogs, a simple, specific and sensitive LC-MS/MS method was established and validated. The separation of the analytes was achieved on an Agilent Eclipse Plus C18column (1.8 μm, 2.1 × 50 mm) with a mobile phase consisting of water and acetonitrile. The flow rate was set at 0.4 mL/min. Quantitation was performed using multiple reaction monitoring (MRM) in negative ion mode, with the transitions atm/z(Q1/Q3) 423.1/367.1 for GB andm/z269.3/170.0 for IS. The linear calibration curve of GB was obtained over the concentration range of 2–200 ng/mL. The intra- and inter-day precisions were <15% and the accuracies were within ±12.7%. The validated method was applied to compare the pharmacokinetic characteristics of GB in healthy beagle dogs after oral administration of three formulations (HME08, GB capsule prepared by hot-melt extrusion technology; LL06, GB pellet prepared by liquid layer technology; conventional GB tablet). The Cmaxvalues of GB from different formulations in beagle dog plasma were 309.2, 192.4 and 66.6 µg/L, and the AUC values were 606.7, 419.1 and 236.2 µg/L·h, respectively. The data suggested that the exposure level of GB from HME08 and LL06 in beagle dog plasma was greatly improved compared with conventional tablets. This study should be helpful for the design and development of oral GB preparations.Keywords:ginkgolide B;hot-melt extrusion;liquid layer;beagle dog plasma;pharmacokinetics;LC-MS/MS
研究领域:
药理学
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药物分析
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2021
·
IF 3.981
Jingxin Gou,Silin Wang,Xu Li,Tian Yin,Haibing He,Yu Zhang,Xing Tang,Wei Xiao,Zhenzhong Wang
Drug microcrystal (MC) is an important category of long acting injections (LAIs), whose release profile is controlled mainly by particle size, crystal form, drug solubility , and other parameters. In this study, a polymeric H + depot composed of alginate was combined with drug MC using ginkgolide B (GB) as model drug to reduce the initial burst release of the drugs with elevated solubility in body fluid. The parameters of GB MC preparation by precipitation, including stabilizer type and amount, phase volume ratio, and stirring rate were investigated. And the particle size/distribution, particle morphology, crystallinity, in vitro release of optimized GB MC were characterized. The in vivo dissolution retardation effect of acidified alginate (SAA) was first confirmed by live imaging using fluorescein as probe. And the pharmacokinetic profiles of different GB MC-polymer blends were investigated by UPLC-MS/MS. The prepared GB MC was spherical-like particles with a mean particle size of 5.863 μm and a span value of 1.634. The crystallinity of GB MC was lowered by the precipitation process compared with that of the crude drug , which resulted in a faster in vitro dissolution with more than 90% of drugs dissolved in 20 min. When administered with SAA, an alginate amount-dependent reduction in C max (1243.5 ± 281.4 ng/mL of GB-SAA, 1:5, 820.9 ± 84.0 ng/mL of GB-SAA, 1:10, 2850.9 ± 1059.3 ng/mL of GB alone and 2476.9 ± 396.4 ng/mL of GB-HPMC E5, 1:10) and prolongation in T max (3.2 ± 1.1 h of GB-SAA, 1:5, 6.4 ± 2.2 h of GB-SAA, 1:10, 1.2 ± 0.45 h of GB alone and 1.4 ± 0.55 h of GB-HPMC E5, 1:10) was noticed, indicating the capability of polymeric H + depot in controlling GB release in vivo . In conclusion, the polymeric H + depot strategy influenced drug dissolution and outward drug diffusion sequentially to retard the initial burst release of drugs with elevated solubility in body fluid.
研究领域:
药剂学
·
生物医学工程
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产品关联
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2017
·
IF 2.759
Jun Hua,Nuo Yin,Beibei Yang,Ji Zhang,Jianhua Ding,Yi Fan,Gang Hu
The accumulation of aggregated forms of the α-Synuclein (α-Syn) is associated with the pathogenesis of Parkinson's disease (PD), a chronic progressive neurodegenerative disorder. Extensive evidences have shown the promising effects of Ginkgo biloba consumption on motor activity after PD. However, the mechanisms underline the α-Syn-induced cell damage and whether ginkgolides exert neuroprotection against this injury are unclear. Here we showed that aggregated recombinant human α-Syn, but not α-Syn monomers, triggered cell injury in cultured human neuroblastoma cell line SH-SY5Y in an apoptosis way by using flow cytometry and western blot assay. Moreover, pre-treatment with the Ginkgolide B (GB) or Bilobalide (BB) protected SH-SY5Y cells against α-Syn-induced cell viability decreases, and reduced cell apoptosis after aggregated α-Syn stimulation. Together, we firstly find that aggregated α-Syn induced cell apoptosis and GB and BB may attenuate aggregated α-Syn-induced cell apoptosis, which gives us an insight into the novel therapy for PD in future.
研究领域:
神经科学
·
药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
POLYMERS FOR ADVANCED TECHNOLOGIES
·
2022
·Vol. 33
·期 10
·3501-3511
·
IF 3.348
Chengying Yang,Honghong Li,Zeyu Wu,Xusheng Huang,An Zhou,Ailing Hui,Rui Liu,Wencheng Zhang
In this article, novel molecularly imprinted polymers based on 3D reduced graphene oxide aerogel (3D RGO-GBMIPs) were successfully fabricated and applied as adsorbents for dispersed solid-phase extraction (DSPE) of ginkgolide B (GB). After being prepared by surface molecular imprinted technology, 3D RGO-GBMIPs were successively characterized by fourier transform infrared spectroscopy, thermogravimetric analysis, Raman spectroscopy, and scanning electron microscope. The results of adsorption experiments revealed that 3D RGO-GBMIPs presented highly selective recognition properties and well reusability. The main variables influencing DSPE efficiency, including extraction solvent, 3D RGO-GBMIPs dosage, category, and volume of eluent, as well as elution time were investigated. The DSPE results showed that 3D RGO-GBMIPs had an obvious effect on the improvement of GB purity in ginkgo biloba extract, with a satisfactory recovery rate and yield. Therefore, 3D RGO-GBMIPs are expected to be applied for the enrichment of GB from complex matrices.
研究领域:
分析化学
·
材料科学
·
植物化学
✓ 已验证
DOI
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Yufeng Dai,Jinxiang Chen,Jialong Fang,Shuxiao Liang,Hao Zhang,Haitao Li,Wei Chen
Thromboxane A 2 (TXA 2 ) is traditionally known for its role in inducing platelet aggregation, but our previous study has discovered its crucial involvement in hepatic glucolipid metabolism and adipose tissue inflammation. Ginkgolide B (GB), a naturally occurring terpene lactone, possesses various pharmacological functions through its antagonism of the platelet activating factor (PAF) receptor. However, the metabolic regulation mechanism link between the anti-obesity efficiency of GB and TXA 2 has remained elusive. Therefore, this research aimed to explore the potential of GB in protecting against obesity by inhibiting TXA 2 synthesis. The results showed that GB inhibited TXA 2 biosynthesis which shares a similar action with eicosapentaenoic acid (EPA) and aspirin. GB treatment ameliorated hyperglycemia by decreasing gluconeogenesis. Additionally, GB supplementation relieved hepatic lipid deposition and dyslipidemia. Furthermore, GB intervention promoted macrophage M2 polarization, thus mitigating adipose tissue inflammation. In summary, our study provided evidence that GB alleviated glucolipid metabolism disorders and adipose tissue inflammation through the inhibition of the TXA 2 pathway. These findings shed light on the mechanism underlying the anti-obesity efficacy of GB and lay foundations for the future use of GB as a functional dietary supplement to alleviate high-fat diet-induced obesity.
研究领域:
药理学
·
代谢
·
炎症
·
营养
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产品关联
DOI
高影响因子
Current Pharmaceutical Analysis
·
2020
·Vol. 16
·期 6
·763-773
·
IF 0.923
Yaro Peter,Nie Jing,Xu Mingcheng,Zeng Kui,Zeng Su
Background: Terpene lactones are major components of ginkgo biloba extract which are used in cardiovascular and degenerative diseases. To study the involvement of transporters in the transport/disposition of ginkgolides A, B, C, and bilobalide, a bioanalytical assay was developed by
LCMS/ MS system for the quantitation of intracellular levels of terpene lactones in cells expressing organic cation transporter 2 (OCT2). Methods: The assay involved an optimized simple sample handling with methyl tert-butyl ether for liquid-liquid extraction and reconstitution in modified
dissolution solution. Pretreatment of samples with 50 μM ascorbic acid and the addition of ascorbic acid and formic acid in dissolution solution significantly reduced matrix effect and stabilized the postpreparative samples. Separations were performed by Zobrax RRHD column (extend-C18 1.8μm,
3.0 x 100mm) and acetonitrile gradient elution. The analysis was carried out in the negative ion scan mode using multiple reaction monitoring. Results: The method was validated for linearity (concentration range of 20-5000nM), accuracy (±13.1%), precision (<11.0%), recovery
(94.31–105.9%), matrix effect (93.8-111.0%) and stability. Finally, the method was applied in the determination of intracellular concentrations of ginkgolides A, B, C, and bilobalide in Madin-Darby canine kidney (MDCK-mock) and MDCK-OCT2 cells in uptake study. Conclusion: The developed
method was successfully validated. Results suggest that OCT2 is involved in the renal disposition of ginkgolide A, B, and bilobalide. This method would foster the study of transport mediated activity via the interaction of ginkgolides and bilobalide with cellular systems.
研究领域:
药理学
·
分析化学
·
药物代谢
✓ 已验证
DOI
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 11
·3998-4008
·
IF 6.6
Mingxi Yang,Xin Wei,Kaibo Pan,Zeli Zhou,Yang Liu,Xiaodan Lv,Bai Yang
Ischemic stroke (IS) is a leading cause of death in the world, and there is still a lack of effective treatments. Ginkgolide B (GB) can antagonize the platelet activating factor receptor and has shown a significant curative effect on cerebral ischemia. However, GB and other drugs for IS have shown poor clinical efficacy due to their inability to cross the blood–brain barrier (BBB). Herein, red fluorescent carbonized polymer dots (CPDs) were developed as biocompatible nanocarriers to deliver GB to the brain tissue. Both in vivo and in vitro experiments verified the ability of GB-CPDs to penetrate the BBB, and GB-CPDs remained in the brain significantly longer than unmodified CPDs. In a rat model of middle cerebral artery occlusion (MCAO), circulatory administration of GB-CPDs effectively reduced cerebral infarct size and neuronal apoptosis, with a significantly better therapeutic effect compared to GB. This study provided a novel GB-based nanodrug that could target the brain with improved efficacy, showing great application potential in central nervous system diseases.
研究领域:
神经科学
·
药学
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）