咖啡酸等小分子酚酸类成分自氧化及聚合机制产物及药理活性研究进展

咖啡酸、丹参素等小分子酚酸类成分有广泛的药理活性,丹参酚酸类成分在复方丹参制剂中发挥着主要的药效作用。据报道,小分子酚酸类成分在一定条件下发生自氧化,可引发自由基链反应。自由基还可通过复杂的机制偶联生成多种聚合物。其中,含1,4-苯并二噁烷结构的聚合物具有抗炎、抗肿瘤和抗病毒等药理活性。笔者对咖啡酸等小分子酚酸类成分的自氧化及自由基聚合机制、产物及药理活性进行综述,以期为阐明含小分子酚酸类成分相关产品的物质基础提供依据,为含1,4-苯并二噁烷结构的物质在化合物筛选、新药开发领域的应用提供参考。     

The Effect of Inert Atmospheric Packaging on Oxidative Degradation in Formulated Granules

No HeadingPurpose. Oxidative degradation of drug substances in pharmaceutical products is well documented and is thought to occur in many cases via autoxidative processes involving headspace molecular oxygen in the primary package. Reducing the headspace oxygen concentration inside a package could thus be an option for reducing oxidative degradation in pharmaceutical products. The purpose of this study is to examine the effect of headspace oxygen concentration and relative humidity (RH) on the oxidative degradation of a model pharmaceutical formulation.Methods. Model formulations, including a drug substance known to exhibit oxidative degradation, at two different drug/excipient ratios were packaged in stoppered glass vials maintained at different oxygen concentrations, (from 0% to 20.9%) and headspace relative humidities and were stored at 40°C. The oxidative degradation was quantified as a function of time.Results. The results clearly show dependence of oxidative degradation on headspace oxygen concen-tration, relative humidity, drug loading and time.Conclusions. The results provided insight into the effectiveness of inert atmospheric packaging (IAP) for protecting oxidation-labile products. In light of these observations, a few strategies for practically implementing inert atmosphere packaging are also presented.     

Decay of granulocyte adherence following isolation from human blood

We studied the rate of decay of granulocyte adherence following isolation from human blood using the nylon-fibre microcolumn technique recently developed in our laboratory. The decay in adherence was found to be evident by 6 h, pronounced by 24 h, and very substantial by 48 h. This decay in adherence can be reversed by incubation at 4 degrees C instead of 37 degrees C. It can also be retarded by incubation with both superoxide dismutase and 2,3-dihydroxybenzoic acid. The data suggests that peroxidation of the granulocyte membrane is a possible mechanism for the decay in granulocyte adherence. These results provide further insight into biological aspects of granulocyte activity, and have implications for the laboratory evaluation of granulocyte function.     

Zea mays,Stigma maydis prevents and extenuates acetaminophen-perturbed oxidative onslaughts in rat hepatocytes

Context: Zea mays L. (Poaceae) Stigma maydis is an underutilized product of corn cultivation finding therapeutic applications in oxidative stress-related disorders.

Objectives: This study investigated its aqueous extract against acetaminophen (APAP)-perturbed oxidative insults in rat hepatocytes.

Materials and methods: Hepatotoxic rats were orally pre- and post-treated with the extract (at 200 and 400?mg/kg body weight) and vitamin C (200?mg/kg body weight), respectively, for 14 days. Liver function, antioxidative and histological analyses were thereafter evaluated.

Results: The APAP-induced marked (p?<?0.05) increases in the activities of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase and the concentrations of bilirubin, oxidized glutathione, protein carbonyls, malondialdehyde, conjugated dienes, lipid hydroperoxides and fragmented DNA were dose-dependently extenuated in the extract-treated animals. The extract also significantly (p?<?0.05) improved the reduced activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase as well as total protein, albumin and glutathione concentrations in the hepatotoxic rats. These improvements may be attributed to the bioactive constituents as revealed by the gas chromatography–mass spectrometric chromatogram of the extract. The observed effects compared favourably with vitamin C and are informative of hepatoprotective and antioxidative attributes of the extract and were further supported by the histological analysis.

Conclusion: The data from the present findings suggest that Stigma maydis aqueous extract is capable of preventing and ameliorating APAP-mediated oxidative hepatic damage via enhancement of antioxidant defence systems.     

Sickle cell disease: role of reactive oxygen and nitrogen metabolites

1. Sickle cell disease (SCD) is an inherited disorder of haemoglobin synthesis that is associated with significant morbidity and mortality due to sequelae of episodic vaso-occlusive events: pain crises and multiorgan damage. The microvascular responses to the initiation, progression and resolution of vaso-occlusive events are consistent with an inflammatory phenotype as suggested by activation of multiple cell types, an oxidatively stressed environment and endothelial cell dysfunction. 2. Decreased anti-oxidant defences in SCD patients and mice are accompanied by activation of enzymatic (NADPH oxidase, xanthine oxidase) and non-enzymatic (sickle haemoglobin auto-oxidation) sources of reactive oxygen species. The resultant oxidative stress leads to dysfunction/activation of arteriolar and venular endothelial cells, resulting in impaired vasomotor function and blood cell-endothelial cell adhesion. 3. Changes in substrate and cofactor availability for endothelial cell nitric oxide synthase may underlie reactive oxygen- and nitrogen-induced events that contribute to SCD-induced vasculopathy. 4. The emerging role of reactive oxygen and nitrogen species in the pathogenesis of SCD provides a platform for the development of novel agents to treat this painful and lethal disease.     

The in vivo auto-oxidation of polyether polyurethane by metal ions

The first large scale use of polyether polyurethane elastomers in long term human implants was as insulation for cardiac and neurologic pacing leads. While the performance of these polymers has generally been very good over a 14-year period, several failure mechanisms have been discovered that involve interactions between the devices, materials and the body. One of these is auto-oxidation of soft segment ether through the intermediate action of certain transition metal ions, derived from conductor wires by corrosion processes. Biologically produced oxidants appear to be an accelerating factor. In this study, Pellethane 2363-80A tubing containing conductor coils or mandrels of various metals or controls were implanted in rabbits. Explants were analyzed as a function of implant time by optical and scanning electron microscopy, electron dispersive analysis by X-ray, stress-strain, FTIR, GPC and AA spectrophotometry. Only cobalt produced bulk oxidative degradation while surface damage was found in the presence of cobalt bearing alloys. No evidence of significant auto-oxidation was found in the presence of silver, nickel, chromium, molybdenum, iron, titanium, platinum, 304 stainless steel, glass or empty tubing. The combination of polyether polyurethane and metals (especially those containing cobalt) in an implantable device must be carefully evaluated for biostability prior to human use.