Euphornin reduces proliferation of human cervical adenocarcinoma HeLa cells through induction of apoptosis and G2/M cell cycle arrest.

BACKGROUND: The plant Euphorbia helioscopia L. has been used in traditional Chinese medicine for treating various disorders such as tuberculosis and edema. The aim of this study was to investigate the effect of euphornin, a bioactive compound isolated from E. helioscopia, on proliferation of human cervical adenocarcinoma HeLa cells by analyzing cell viability, rate of apoptosis, and cell cycle progression. MATERIALS AND METHODS: The sulforhodamine B assay was used to study the effect of euphornin on the proliferation of HeLa cells. Morphological changes to cell nuclei were identified after Hoechst 33342 staining. Mitochondrial membrane depolarization (MMP) was analyzed after staining with JC-1 dye. The influence of euphornin on the apoptosis rate was analyzed by Annexin V/propidium iodide double staining. Fluorescence-activated cell sorting was applied to investigate the influence of euphornin on cell cycle progression. Proteins were obtained from HeLa cells and analyzed by Western blots. RESULTS: A cell viability assay showed that euphornin inhibited proliferation of HeLa cells in a dose-dependent and time-dependent manner. Euphornin also induced apoptosis in a concentration-dependent manner, with the rates of apoptosis ranging from 25.3% to 52.6%. A high concentration of euphornin was found to block HeLa cells at the G2/M stage. A Western blot analysis suggested that euphornin might exhibit antitumor activity by inducing apoptosis. Euphornin treatment altered the ratio of Bax/Bcl-2 in HeLa cells, which led to the release of cytochrome complex. The levels of cleaved caspase-3, caspase-8, caspase-9, and caspase-10 were also markedly increased by euphornin treatment. Analysis of cell cycles indicated that euphornin induced cell cycle arrest by increasing the level of the phospho-CDK1 (Tyr15) protein. The various assays demonstrated that euphornin treatment resulted in a significant suppression of cell growth accompanied by G2/M cell cycle arrest and increased rate of apoptosis via mitochondrial and caspase pathways. CONCLUSION: Our findings suggest that euphornin has the potential to be used as a cancer therapeutic agent against human cervical adenocarcinoma.

Transdermal application of azithromycin-amlodipine-heparin gel enhances survival of infected random ischaemic flap.

BACKGROUND: Flap necrosis is generally regarded as the result of vasospasm, thrombosis, and infection. METHODS: To improve skin flap survival and lower the risk of side effects due to systemic drug delivery, we formulated and evaluated compound gels for transdermal application. The transdermal delivery of 1% azithromycin (AZM), 0.5% amlodipine besylate (AB), and 300 IU/g low molecular weight heparin (LMWH) in compound gels, singly or in combinations, was measured across rat skin in vitro. The effects of AB and LMWH on flap blood circulation was investigated using fluorescein angiography, by transdermally applying the gel onto the surface of an in vivo ischaemic flap rat model; concentrations of the drugs were detected in both blood plasma and flap tissue at assigned timepoints. Finally, infected ischaemic flaps were treated to evaluate their anti-inflammatory effects and sizes of flap survival area. RESULTS: Each drug efficiently penetrated the in vitro skin in a time-dependent manner. In the in vivo ischaemic flaps, AB or LMWH increased the blood supply. All gel formulations that included AZM were associated with less flap inflammation. The surviving areas after treatment with AZM+LMWH or AZM+AB were significantly larger than that treated with the AZM-only gel, and the largest surviving area was that treated with AZM+AB+LMWH. Gels containing no AZM could not decrease flap inflammation or increase flap survival. CONCLUSION: Transdermal application of a compound gel with AZM, AB, and LMWH combined is a promising method to prevent and treat flap infection, improve blood circulation, and increase the survival of infected ischaemic flaps.

ß-methasone-containing biodegradable poly(lactide-co-glycolide) acid microspheres for intraarticular injection: effect of formulation parameters on characteristics and in vitro release.

A sustained drug release system based on the injectable poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with ß-methasone was prepared for localized treatment of rheumatic arthritis. The microscopy and structure of microspheres were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR). The effects of various formulation parameters on the properties of microspheres and in vitro release pattern of ß-methasone were also investigated. The results demonstrated that increase in drug/polymer ratio led to increased particle size as well as drug release rate. Increase in PLGA concentration led to increased particle size, but decreased burst release. The drug encapsulation efficiency increased sharply by increasing polyvinyl alcohol (PVA) concentration in the aqueous phase from 1.5 to 2.0%. ß-methasone release rate decreased considerately with decreasing OP (organic phase)/AP (aqueous phase) volume ratio. Stirring rate had significantly influence on the particle size and encapsulation efficiency. Independent of formulation parameters, ß-methasone was slowly released from the PLGA microspheres over 11 days. The drug release profile of high drug loaded microspheres agree with Higuchi equation with a release mechanism of diffusion and erosion, that of middle drug loaded microspheres best agreed with Hixcon-Crowell equation and controlled by diffusion and erosion as well. The low drug loaded microspheres well fitted to logarithm normal distribution equation with mechanism of purely Fickian diffusion.

[Preparation and quality evaluation of fufangxiaoyepipa dispersible tablets].

OBJECTIVE: To study the preparation of fufangxiaoyepipa dispersible tablets and evaluate its quality. METHODS: Using the disintegration time as index to screen out the best prescription of the dispersible tablets by orthogonal design. RESULTS: The prescription assembly was 40% of extraction, 15% of MCC, 18% of CCMC-Na, 25% of Calcium sulfate, 2% of Magnesium stearate, the disintegration time met the provision of Pharmacopoeia. CONCLUSION: The dispersible tablets dissolve faster and disperse uniformly and the dissolution percent in vitro is obviously superior to the conventional tablets, improving the bioavailability of the preparation.