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1.
J Ethnopharmacol ; 335: 118622, 2024 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-39053719

RESUMEN

ETHNO-PHARMACOLOGICAL RELEVANCE: Huangqi Gegen decoction (HGD), which comprises Astragali Radix (AR) and Puerariae Radix (PR), is widely used to treat thrombosis in China. However, the mechanism underlying its synergistic effect in thrombosis treatment remains unclear. AIM OF THE STUDY: Following PR administration, low plasma exposure was reported for its primary ingredients. In this regard, this study examined the effect of AR on PR's antithrombotic efficacy with respect to the impact of Astragalus Polysaccharide (APS) on the oral delivery of Puerarin (PUE). MATERIALS AND METHODS: To evaluate the synergistic effect of HGD, a thrombus mice model was established via intraperitoneal injection of carrageenan. After treatment, histopathological observations were made, and the proportion of thrombus length in the tail, as well as the plasma APTT, PT, INR, and FIB levels, were detected. Molecular docking was employed to assess the PR ingredients that could inhibit the HMGB1/NF-κB/NLRP3 pathway. The Pharmacokinetics of PR ingredients in rats were also compared between the PR and HGD groups. Moreover, the effect of APS on the solubility, intestinal absorption, and pharmacokinetics of PUE was evaluated. Furthermore, the impact of APS on the antithrombotic efficacy of PUE was assessed. RESULTS: In mice, AR enhanced the antithrombotic effect of PR. This improved PR effect was associated with isoflavones-induced downregulation of the HMGB1/NF-κB/NLRP3 pathway. The synergistic effect resulting from the compatibility of HGD components was primarily achieved by improving the plasma exposure of PR isoflavones. Specifically, APS enhanced PUE's water solubility through the formation of self-assembly Nanoparticles, increasing its intestinal absorption and oral bioavailability, which, in turn, suppressed the HMGB1/NF-κB/NLRP3 pathway, thus improving its antithrombotic effect. CONCLUSIONS: Our findings revealed that APS improved PUE's plasma exposure, enhancing its inhibitory effect on the HMGB1/NF-κB/NLRP3 pathway. This mechanism presents a key aspect of the synergistic effect of HGD compatibility in thrombosis treatment.


Asunto(s)
Planta del Astrágalo , Sinergismo Farmacológico , Medicamentos Herbarios Chinos , Isoflavonas , Polisacáridos , Trombosis , Animales , Isoflavonas/farmacología , Isoflavonas/administración & dosificación , Isoflavonas/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Polisacáridos/farmacología , Polisacáridos/administración & dosificación , Masculino , Administración Oral , Trombosis/tratamiento farmacológico , Ratones , Planta del Astrágalo/química , Fibrinolíticos/farmacología , Fibrinolíticos/administración & dosificación , Pueraria/química , Modelos Animales de Enfermedad , Simulación del Acoplamiento Molecular , Astragalus propinquus/química , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo
2.
Artículo en Inglés | MEDLINE | ID: mdl-33936246

RESUMEN

Traction of cervical spine is an effective method for the treatment of cervical spondylotic radiculopathy (CSR). In this study, a cervical tractor named traction exercise neck brace (TENB) was used to evaluate its effect on the patients with CSR. Forty CSR volunteers were recruited and randomly divided into two groups. One group was subjected to cervical muscle exercise with TENB under static traction condition. Another group was subjected to (JOBT) as controls. Symptoms of CSR were evaluated by the visual analogue scale (VAS) and neck disability index (NDI). Imaging characteristics were assessed by curvature of the cervical spine and size of the intervertebral foramen. A finite element (FE) analysis model of cervical spine was established by 3D reconstruction to simulate the TENB traction, which evaluates the biomechanical performance. Results showed that TENB significantly reduced scores of VAS and NDI in subjects, and this improved effect on symptoms of pain and radiculopathy is better than that of JOBT. TENB also improved the cervical curvature and enlarged intervertebral foramen at the C4-C6 level. Moreover, FE analysis found that simulated TENB traction increased the spacing of intervertebral foramen, intervertebral disc, and zygapophyseal and uncovertebral joints and changed the stress distribution on the facet joints and nucleus pulposus. This study demonstrates that TENB relieves the symptoms of CSR by adjusting structure of cervical vertebra and restoring its biomechanical performance, which may be a promising instrument in the treatment of CSR.

3.
Biointerphases ; 13(3): 03B401, 2018 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-29320860

RESUMEN

As an antibiotic that prevents and treats infections caused by Gram-positive bacteria such as Staphylococcus aureus, vancomycin incorporated in a biodegradable polymer poly(lactide-co-glycolide) provides opportunities to construct controlled-release drug delivery systems. Developments associated with this promising system have been largely concentrated on areas of drug delivery kinetics and biodegradability. In order to provide surface analytical approaches to this important system, the authors demonstrate applicability of time-of-flight secondary ion mass spectrometry (TOF-SIMS) in three-dimensional molecular imaging for a model system consisting of alternating layers of ploy(lactide-co-glycolide) and vancomycin. TOF-SIMS imaging clarified that the two chemicals can undergo phase separation when dimethyl sulfoxide is used as the solvent. The authors identified two diagnostic ions that are abundant and structural moieties of vancomycin. The results on TOF-SIMS imaging and depth profiling vancomycin provide useful information for further applications of TOF-SIMS in the development of antibiotic drug delivery systems involving the use of vancomycin.


Asunto(s)
Antibacterianos/análisis , Portadores de Fármacos/química , Imagenología Tridimensional/métodos , Poliglactina 910/química , Espectrometría de Masa de Ion Secundario/métodos , Propiedades de Superficie , Vancomicina/análisis , Dimetilsulfóxido , Portadores de Fármacos/síntesis química , Sistemas de Liberación de Medicamentos , Solventes
4.
Mater Sci Eng C Mater Biol Appl ; 78: 1172-1178, 2017 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-28575954

RESUMEN

Loading antibiotics in a biodegradable polymer matrix is an excellent way to control its release kinetics, which eliminates side effects caused by conventional administrations of the drug. This approach is especially beneficial for bone regeneration when using a scaffold made of a biodegradable polymer loaded with drug agents capable of controllable releases. In this case, the scaffold serves as a mechanical support to tissue formation and the drug agents may provide biomolecules to assist the tissue formation and/or provide antibiotics to prevent tissues from infections. Towards this goal, we have developed an approach to make vancomycin-loaded poly(lactide-co-glycolide) (PLGA) microspheres, from which we made scaffolds by compression molding. In this article we concentrate on characterizing the porosity and drug release profiles, as well as verifying shape-memory effect of the scaffolds. The scaffold was biodegradable and showed a much slower drug release profile than microspheres. We confirmed that our PLGA scaffolds recovered to their permanent shapes when heated to 45°C. We believe that these scaffolds will find applications in bone regeneration where both the use of antibiotics against infection and accommodation to spatial restrictions may be required.


Asunto(s)
Vancomicina/química , Preparaciones de Acción Retardada , Sistemas de Liberación de Medicamentos , Ácido Láctico , Microesferas , Poliglactina 910 , Ácido Poliglicólico , Porosidad , Andamios del Tejido
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