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Preparation of total flavonoid-liposomes of Lonicerae Japonicae flos and their inhibitory effect on methicillin-resistant Staphylococcus aureus
Journal of Army Medical University 2024, 46(24): 2755-2764
Published: 30 December 2024
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Objective

To prepare the liposomes of total flavonoids from Lonicerae Japonicae flos (LJFTF) and evaluate their inhibitory effect on methicillin-resistant Staphylococcus aureus(MRSA).

Methods

LJFTF liposomes were prepared by ethanol injection.Then the preparation process was optimized by star point design-effect surface method, with the concentrations of phospholipid, mass ratio of phospholipid to cholesterol and mass concentration of LJFTF as the influencing factors, and the encapsulation rate and drug-loading rate as evaluation indicators.The obtained liposomes were characterized by observing their properties, measuring particle size, polymer dispersity index (PDI) and Zeta potential through laser particle size analyzer.High performance liquid chromatography (HPLC) was used to determine the release rate of the liposomes.The antibacterial activity of the liposomes against MRSA was observed by plate method and live/dead staining, and the inhibitory effect of the liposomes on MRSA biofilm was observed by crystal violet staining.

Results

After optimization and verification, the best preparation process was as follows: phospholipid concentration 35.0 mg/mL, phospholipid to cholesterol mass ratio 15.0, and LJFTF concentration 5.7 mg/mL.The prepared liposomes were light yellow emulsion, with an average encapsulation rate of 86.37%(RSD=0.37%, n=3), and an average drug-loading rate of 11.69%(RSD=0.09%, n=3), a particle size of 173.60±1.07 nm, a PDI value of 0.15±0.05, and a Zeta potential of-4.86±0.60 mV.The free LJFTF was completely released within 4 h from the dialysis bag, and the in vitro cumulative release of LJFTF was (59.44±3.58)% at 12 h and (63.58±5.78)% at 30 h.Plate and live/dead staining showed that the prepared liposomes significantly inhibited the growth and promoted the death of MRSA strain.Crystal violet staining displayed that the liposomes significantly inhibited the formation of MRSA biofilm (P < 0.001), with significant difference in comparison with same dose of LJFTF (P < 0.001).

Conclusion

LJFTF liposomes are successfully prepared, and the formulation process has been optimized.The liposomes show significant anti-MRSA activity in vitro.

Issue
Signal mining and analysis for adverse events of avatrombopag based on FAERS
Journal of Army Medical University 2024, 46(4): 369-376
Published: 28 February 2024
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Objective

To mine the adverse drug events (ADE) signal of avatrombopag, an effective drug for thrombocytopenia treatment, based on real world data in order to provide reference for its clinical safety application.

Methods

The OpenVigil2.1 pharmacovigilance platform was used to obtain the ADE report data of avatrombopag from May 2018 to March 2023 in the database of FDA adverse event reporting system (FAERS).The ADE signals were classified and described by the system organ class (SOC) and preferred term (PT) of the ADE terminology set in the Medical Dictionary for Regulatory Activities (MedDRA), and reporting odds ratio (ROR) and UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard were used to detect the positive ADE signals.

Results

A total of 1879 ADE reports related to avatrombopag were obtained, 24 SOCs were involved, and 28 positive ADE signals were detected at PT level.Among these signals, the strongest ones were renal vein thrombosis, portal vein thrombosis and graft versus host disease, while the reports accounting for the largest numbers were headache, fatigue and asthenia.There were 8 ADE signals discovered newly, that is, seasonal allergy, back disorder, musculoskeletal discomfort, flatulence, hypersomnia, rash macular, emotional disorder, and rhinorrhoea.

Conclusion

For clinical use of avatrombopag, clinicians should not only concern the risk of thrombosis, but also pay close attention to ADE signals such as seasonal allergy, back disorder, musculoskeletal discomfort, flatulence, hypersomnia, rash macular, emotional disorder, and rhinorrhoea that are not documented in the instructions.

Issue
Mechanism of Astragalus membranaceus in treatment for vascular dementia based on network pharmacology and molecular docking
Journal of Army Medical University 2023, 45(10): 1070-1079
Published: 30 May 2023
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Objective

To investigate the mechanism of Astragalus membranaceus(AM)in the treatment of vascular dementia(VD)by network pharmacology and molecular docking.

Methods

The active components of AM were collected from TCMSP database, and the targets of active components were predicted in TargetNet database according to the SMILES. The VD targets were collected by GeneCards database, and the common targets of active components and VD was calculated to obtain the potential targets of AM in the treatment of VD. The active components-target network was constructed by Cytoscape 3.9.1 software. The potential targets of AM in the treatment of VD were imported into STRING database to construct protein-protein interaction(PPI)network, which was analyzed to obtain core targets. The core targets were imported into DAVID database to perform Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis. The molecular docking was performed to assess the affinity of main active components of AM and the corresponding VD core targets via AutoDock software.

Results

A total of 20 active components of AM were collected, including jaranol, isorhamnetin, isoflavanone, kaempferol and quercetin, and a total of 102 predicted targets were obtained. A total of 3 556 VD targets were screened, 71 common targets of AM and VD were calculated, and 36 core targets were obtained by PPI analysis, including SLC6A4, ESR1, PTGS2, ABCB1 and AR. A total of 187 GO items and 32 KEGG pathways were enriched, mainly focusing on neurological function, hormone signal and angiogenesis. Molecular docking showed good affinity between the main active components of AM and VD core targets.

Conclusion

AM treats VD mainly by regulating neurological function, hormone signal and angiogenesis.

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