Preparation and Physicochemical and Pharmacokinetic Characterization of Ginkgo Lactone Nanosuspensions for Antiplatelet Aggregation

Rui, Tianqi; Liang, Zhang; Qiao, Hongzhi; Huang, Ping; Qian, Shuai; Li, Junsong; Chen, Zhipeng; Fu, Tingming; Di, Liuqing; Cai, Baochang

doi:10.1016/j.xphs.2015.10.002

Cited by 22 publications

(7 citation statements)

References 30 publications

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“…[23][24][25][26] Studies also have shown that GBE may inhibit platelet aggregation induced by AA, ADP, thrombin, collagen and PAF. [27][28][29][30] In addition, GBE in combination with cilostazol may potentiate the antiplatelet effects of cilostazol with no prolongation of bleeding time or coagulation time in patients. 31 Metaanalyses have shown that GBE did not increase the risk of bleeding, either alone or in combination with antiplatelet/anticoagulants.…”

Section: Introductionmentioning

confidence: 99%

The Synergistic Effect of Ginkgo biloba Extract 50 and Aspirin Against Platelet Aggregation

Huo

et al. 2021

DDDT

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We aimed to investigate potential synergistic antiplatelet effects of Ginkgo biloba extract (GBE50) in combination with aspirin using in vitro models. Methods: Arachidonic acid (AA), platelet activating factor (PAF), adenosine 5ʹ-diphosphate (ADP) and collagen were used as inducers. The antiplatelet effects of GBE50, aspirin and 1:1 combination of GBE50 and aspirin were detected by microplate method using rabbit platelets. Synergy finder 2.0 was used to analyze the synergistic antiplatelet effect. The compounds in GBE50 were identified by UPLC-Q/TOF-MS analysis and the candidate compounds were screened by TCMSP database. The targets of candidate compounds and aspirin were obtained in TCMSP, CCGs, Swiss target prediction database and drugbank. Targets involving platelet aggregation were obtained from GenCLiP database. Compound-target network was constructed and GO and KEGG enrichment analyses were performed to identify the critical biological processes and signaling pathways. The levels of thromboxane B2 (TXB2), cyclic adenosine monophosphate (cAMP) and PAF receptor (PAFR) were detected by ELISA to determine the effects of GBE50, aspirin and their combination on these pathways. Results: GBE50 combined with aspirin inhibited platelet aggregation more effectively. The combination displayed synergistic antiplatelet effects in AA-induced platelet aggregation, and additive antiplatelet effects occurred in PAF, ADP and collagen induced platelet aggregation. Seven compounds were identified as candidate compounds in GBE50. Enrichment analyses revealed that GBE50 could interfere with platelet aggregation via cAMP pathway, AA metabolism and calcium signaling pathway, and aspirin could regulate platelet aggregation through AA metabolism and platelet activation. ELISA experiments showed that GBE50 combined with aspirin could increase cAMP levels in resting platelets, and decreased the levels of TXB2 and PAFR. Conclusion:Our study indicated that GBE50 combined with aspirin could enhance the antiplatelet effects. They exerted both synergistic and additive effects in restraining platelet aggregation. The study highlighted the potential application of GBE50 as a supplementary therapy to treat thrombosis-related diseases.

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Section: Introductionmentioning

confidence: 99%

The Synergistic Effect of Ginkgo biloba Extract 50 and Aspirin Against Platelet Aggregation

Huo

et al. 2021

DDDT

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“…RDI is defined as the following equation. D and D 0 are the mean particle size of reconstituted suspension and nanosuspension before spray-drying, respectively [ 36 ]. When the RDI value is near to 100%, it means that the dried suspension powder can be completely redispersed to nanoparticle before spray-drying.…”

Section: Methodsmentioning

confidence: 99%

Development and Evaluation of a Reconstitutable Dry Suspension to Improve the Dissolution and Oral Absorption of Poorly Water-Soluble Celecoxib

Kim

Park²,

Park

et al. 2018

Pharmaceutics

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This study aims at developing and evaluating reconstitutable dry suspension (RDS) improved for dissolution rate, oral absorption, and convenience of use of poorly water-soluble celecoxib (CXB). Micro-sized CXB particle was used to manufacture nanosuspension by using bead milling and then RDS was made by spray-drying the nanosuspension with effective resuspension agent, dextrin. The redispersibility, morphology, particle size, crystallinity, stability, dissolution, and pharmacokinetic profile of the RDS were evaluated. RDS was effectively reconstituted into nanoparticles in 775.8 ± 11.6 nm. It was confirmed that CXB particles are reduced into needle-shape ones in size after the bead-milling process, and the description of CXB was the same in the reconstituted suspension. Through the CXB crystallinity study using differential scanning calorimetry (DSC) and XRD analysis, it was identified that CXB has the CXB active pharmaceutical ingredient (API)’s original crystallinity after the bead milling and spray-drying process. In vitro dissolution of RDS was higher than that of CXB powder (93% versus 28% dissolution at 30 min). Furthermore, RDS formulation resulted in 5.7 and 6.3-fold higher area under the curve (AUC∞) and peak concentration (Cmax) of CXB compared to after oral administration of CXB powder in rats. Collectively, our results suggest that the RDS may be a potential oral dosage formulation for CXB to improve its bioavailability and patient compliance.

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“…In anticoagulant research, the advantageous low toxicity of natural substances has attracted attention. Currently, far more studies are focusing on natural products and have discovered some natural products such as the ginkgo biloba leaf extract that can coagulate blood effectively [21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Vitis labrusca Extract (HP01) Improves Blood Circulation and Lipid Metabolism in Hyperlipidemic Rats

Chang

Kim

2020

Evidence-Based Complementary and Alternative Medicine

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Excessive intake of high-lipid foods and lifestyle changes can easily cause hyperlipidemia. Hyperlipidemia is clinically considered a major risk factor for cardiovascular disease, which is the second leading cause of death worldwide. In this study, the effects of a Vitis labrusca extract (HP01) on coagulation, platelet aggregation, and lipid metabolism were investigated in hyperlipidemic rats. A rat model of high-fat diet- (HFD-) induced hyperlipidemia was used. Hemostatic parameters and lipid levels were investigated after HP01 treatment of hyperlipidemic rats. Different doses of HP01 (200 mg/kg/day and 400 mg/kg/day, p.o.) were administered for 3 weeks, and prothrombin time (PT), activated partial thromboplastin time (aPTT), and platelet aggregation and bleed time (BT) were determined. The levels of thromboxane B(2) (TXB(2)) and serotonin were measured using enzyme-linked immunosorbent assay kits. Simultaneously, hepatic function and blood fat indexes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), malondialdehyde (MDA), and glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were also measured. In comparison with the data obtained for rats in the untreated HFD group, HP01 (200 mg/kg) treatment prolonged PT but did not affect aPTT. HP01 treatment did not alter plasma TXB(2), PGI2, or serotonin levels. However, HP01 showed some effects in improving liver function by reducing the levels of hepatic lipids. ALT, MDA, and hepatic TG levels significantly decreased, whereas GSH, GPx, CAT, and SOD levels significantly increased. These results confirm the HP01 extract will improve thromboplastic and the liver metabolic disorders in hyperlipidemia by oxidative stress response.

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Preparation and Physicochemical and Pharmacokinetic Characterization of Ginkgo Lactone Nanosuspensions for Antiplatelet Aggregation

Cited by 22 publications

References 30 publications

The Synergistic Effect of Ginkgo biloba Extract 50 and Aspirin Against Platelet Aggregation

The Synergistic Effect of Ginkgo biloba Extract 50 and Aspirin Against Platelet Aggregation

Development and Evaluation of a Reconstitutable Dry Suspension to Improve the Dissolution and Oral Absorption of Poorly Water-Soluble Celecoxib

Vitis labrusca Extract (HP01) Improves Blood Circulation and Lipid Metabolism in Hyperlipidemic Rats

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