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
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DOI
高影响因子
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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产品关联
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
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chemosensors
·
2023
·Vol. 12
·期 1
·6
·
IF 4.2
Qing Liu,Meifang Jiang,Jun Wang,Dandan Wang,Yi Tao
The decolorization process plays a pivotal role in refining Ginkgo ketone ester by primarily eliminating ginkgolic acids, a toxic component. Presently, the conventional testing method involves sending samples for analysis, causing delays that impact formulation production. Hence, the development of a rapid process control method becomes imperative. This study introduces a swift detection approach for three ginkgolic acids during Ginkgo ketone ester’s decolorization. Initially, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method assessed ginkgolic acid C13:0, ginkgolic acid C15:1, and ginkgolic acid C17:1 concentrations in 91 decolorized solution samples, establishing reference values. Subsequently, using a portable Raman spectrometer, Raman spectra of the decolorized liquid within the 3200–200 cm−1wavelength range were collected. Ultimately, employing partial least squares regression (PLSR) and ResNeXt50 deep learning algorithms, two quantitative calibration models correlated the ginkgolic acid content to Raman spectral data. Both models exhibited high predictive accuracy, with the ResNeXt50 model demonstrating superior performance. The prediction set correlation coefficients (Rp2) for ginkgolic acid C13:0, ginkgolic acid C15:1, and ginkgolic acid C17:1 were 0.9962, 0.9971, and 0.9974, respectively, with root mean square error of prediction (RMSEP) values of 0.0144, 0.0130, and 0.0122 μg/mL. In contrast, the PLSR model yieldedRp2values of 0.9862, 0.9839, and 0.9480, with RMSEP values of 0.0273, 0.0305, and 0.0545 μg/mL for the three ginkgolic acids. The ResNeXt50 model not only showcased higher precision but also enhanced interpretability, as analyzed through gradient-weighted class activation mapping (Grad-CAM). The integration of Raman spectroscopy and the ResNeXt50 quantitative calibration model furnishes a real-time and precise approach to monitor ginkgolic acid content in the decolorized solution during Ginkgo ketone ester preparation. This significant advancement establishes a robust framework for implementing quality control measures in the decolorization process.
研究领域:
分析化学
·
药学
✓ 已验证
产品关联
DOI
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
✓ 已验证
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
·
神经科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2014
·
IF 2.939
HanLiang Guan,Dawei Qian,Hao Ren,Wei Zhang,Hui Nie,Erxing Shang,Jinao Duan
Ethnopharmacological relevance Extracts from Ginkgo biloba L. leaves confer their therapeutic effects through the synergistic actions of flavonoid and terpenoid components, but some non-flavonoid and non-terpenoid components also exist in this extract. In the study of this paper, an investigation was carried out to compare the pharmacokinetic parameters of fourteen compounds to clarify the influences of non-flavonoid and non-terpenoid fraction (WEF) on the pharmacokinetics profile of the flavonoid fraction (FF) and the terpene lactone fraction (TLF) from Ginkgo biloba extracts . Materials and methods A selective and sensitive UPLC–MS/MS method was established to determine the plasma concentrations of the fourteen compounds to compare the pharmacokinetic parameters after orally administration of FF, TLF, FF–WEF, FF–TLF, TLF–WEF and FF–TLF–WEF with approximately the same dose. At different time points, the concentration of rutin (1), isoquercitrin (2), quercetin 3-O-[4-O-(-β-D-glucosyl)-α-L-rhamnoside] (3), ginkgolide C (4), bilobalide (5), quercitrin (6), ginkgolide B (7), ginkgolide A (8), luteolin (9), quercetin (10), apigenin (11), kaempferol (12), isorhamnetin (13), genkwanin (14) in rat plasma were determined and main pharmacokinetic parameters including T 1/2 , T max , C max and AUC were calculated using the DAS 3.2 software package. The statistical analysis was performed using the Student׳s t-test with P <0.05 as the level of significance. Results FF and WEF had no effect on the pharmacokinetic behaviors and parameters of the four terpene lactones, but the pharmacokinetic profiles and parameters of flavonoids changed while co-administered with non-flavonoid components. It was found that C max and AUC of six flavonoid aglycones in group FF–WEF, FF–TLF and FF–TLF–WEF had varying degrees of reduction in comparison with group FF, especially in group FF–TLF–WEF. On the contrary, the values of C max , T max and AUC of four flavonoid glycosides in group FF–TLF–WEF were significantly increased compared with those in group FF. Conclusions These results indicate that non-flavonoid components in Ginkgo biloba extracts could increase the absorption and improve the bioavailability of flavonoid glycosides but decrease the absorption and reduce the bioavailability of flavonoid aglycones.
研究领域:
药理学
·
药学
·
民族药理学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
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
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 39
·22136-22145
·
IF 2.936
Jiawei Han,Xin Wang,Jingxian Wang,Lingchong Wang,Lihua Chen,Junsong Li,Wen Li
The Quality-by-Design (QbD) approach was employed to investigate the fluid-bed coating process for the conversion of ginkgo lactone (GL) liquid nanosuspensions into dried nanosuspensions. The effects of critical process variables including inlet air temperature, inlet air capacity and atomizing air pressure were investigated. The particle size and percent yield were optimized using a full factorial design. A Box-Behnken design (BBD) was employed to generate the response surface and optimize process conditions. Multi-linear regression and one-way ANOVA were used to analyze the relationship between critical variables and responses. The results showed that all three selected variables were significant factors (p < 0.05) affecting the particle size. Higher inlet temperature, inlet air capacity or atomizing air pressure will cause an increase of particle size. In addition, the percent yield primarily depended on the inlet air temperature and inlet air capacity (p < 0.05). A higher percent yield was obtained at a higher inlet air temperature or inlet air capacity. The optimal conditions for BBD, including inlet air temperature, inlet air capacity and atomizing air pressure, were set at 40 °C, 11.6 Nm3 and 0.7 bar, respectively. Compared with the raw GLs, the optimized products presented an amorphous state and possessed much faster dissolution. The particle size, percent yield, PDI, zeta-potential and redispersibility index of the optimized products were 254.3 ± 9.8 nm, 82.36 ± 1.87%, 0.155 ± 0.02, −32.9 ± 3.8 mV and 113 ± 4.4% (n = 3), respectively. These results indicate that fluid-bed coating technology based on a QbD approach was sufficient for the solidification of nanosuspensions.
研究领域:
制药工程
·
药物化学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2022
·Vol. 14
·期 5
·923
·
IF 6.525
Ting Zhang,Xixi Li,Juewen Xu,Jingbao Shao,Meihong Ding,Senlin Shi
As a biopharmaceutics classification system (BCS) class IV drug, breviscapine (Bre) has low solubility in water, poor chemical stability, a short biological half-life and rapid removal from plasma. This paper prepared a Bre nanosuspension (Bre-NS) by an ultrasound-assisted anti-solvent precipitation method. Characterization of Bre-NS was studied using a Box–Behnken design concerning drug concentration in DMSO, an anti-solvent-to-solvent ratio, and sonication time. Under the optimized conditions of 170 mg/mL for the drug concentration, a 1:60 solvent-to-anti-solvent ratio, and a 9 min sonication time, the particle size of Bre-NS was 303.7 ± 7.3 nm, the polydispersity index was 0.178 ± 0.015, and the zeta potential was −31.10 ± 0.26 mV. Combined with the results from differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform-infrared spectroscopy (FT-IR), the findings indicated that the crystal form and chemical structure of Bre-NS did not change during the entire process. The optimized formulation displayed good stability, increased solubility, and better in vitro release. Therefore, the results of this study can be a reference for the delivery system design of insoluble active components and effective parts in traditional Chinese medicine.Keywords:breviscapine;nanosuspension;Box–Behnken design
研究领域:
药学
·
药物递送系统
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR MODELING
·
2020
·Vol. 26
·期 8
·1-10
·
IF 1.346
Huang Xusheng,Zhang Wencheng,Wu Zeyu,Li Honghong,Yang Chengying,Ma Wanru,Hui Ailing,Zeng Qingmei,Xiong Baoyi,Xian Zhaojun
In this study, the preparation of molecularly imprinted polymers for bilobalide (BBMIPs) was successfully achieved by bulk polymerization with methacrylamide (MAM), trimethylolpropane triacrylate (TMPTA), and acetonitrile (ACN) as functional monomer, cross-linker, and solvent, respectively. After Gaussian software simulation and single factor experiments, the prepared MIPs with a molar ratio of 1:4:15 for BB-MAM-TMPTA were systematically characterized. The hydrogen bonding interaction between BB and MAM was confirmed by a combination of FTIR and NMR analysis. Thermal gravimetric analysis results displayed that MIPs have excellent thermal stability under high temperature. Additionally, the average pore size and surface area of MIPs were found to be higher than those of NIPs through nitrogen adsorption results. The results of static adsorption and kinetic adsorption suggested that the adsorption equilibrium concentration was 0.6 mg/mL and the equilibrium time was 5 h, and the Langmuir and pseudo-second-order kinetic models were proven to fit with static and kinetic adsorption behaviors, respectively. Meanwhile, the selective adsorption study revealed that MIPs show high adsorption and great selectivity towards BB in comparison with other substances having similarly structure. MIPs also possessed a good performance on reusability, maintaining a high recovery rate after being reused 5 times. The application experiment further indicated that MIPs can effectively separate BB from low purity samples. Therefore, the prepared MIPs had a great potential for BB separation.
研究领域:
分析化学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POLYMER INTERNATIONAL
·
2021
·Vol. 71
·期 3
·301-309
·
IF 2.99
Xusheng Huang,Qingsong Liu,Wencheng Zhang,Zeyu Wu,Yunchun Wang,Jianwen Li,Baoyi Xiong,Zhaojun Xian
The preparation of raw materials is an important prerequisite for studying the function of natural active ingredients. Here, the preparation of MWCNTs/ZIF-67@MIPs based on surface molecular imprinting technology for the separation of bilobalide (BB) from real samples was proposed. The successful preparation of MWCNTs/ZIF-67@MIPs was demonstrated using several techniques. Adsorption equilibrium was achieved when the time was 4 h, and the rate of adsorption calculated from the dynamic adsorption results was 14.2 μg mL –1 h –1 . The maximum adsorption amount for MWCNTs/ZIF-67@MIPs of BB was calculated to be 59.2 mg g –1 , which was more than three times that for MWCNTs/ZIF-67@NIPs (23.1 mg g –1 ), and the Freundlich isotherm model and pseudo-second-order kinetic model were more suitable for the explanation of isothermal and kinetic adsorption behaviors, respectively. The results of selective adsorption indicated that MWCNTs/ZIF-67@MIPs show excellent selectivity and specificity for BB compared to structurally similar compounds such as ginkgolides A, B and C, with an excellent imprinting factor (2.83). The results of reuse studies indicated that MWCNTs/ZIF-67@MIPs exhibited great reproducibility with a recovery rate of 70.8% after repeated use for five times. Finally, the developed MWCNTs/ZIF-67@MIPs were used as a solid-phase extraction sorbent to directly separate BB from treated gingko leaf extract and crude extract of BB, and the results suggested that the purity of BB in the two samples was increased by about 30%, and the recoveries reached 68.34% and 71.54%, respectively. Meanwhile, the separation effect of MWCNTs/ZIF-67@MIPs on BB was better than that of BBMIP prepared by bulk polymerization. © 2021 Society of Industrial Chemistry.
研究领域:
分析化学
·
天然产物化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）