当归内酯清除自由基及抗氧化活性的研究

目的 研究当归内酯清除自由基和抗氧化活性的作用.方法 采用体外实验研究当归内酯对1-1-二苯基苦基苯肼自由基(DPPH·)和·OH的清除作用,自身还原能力的强弱,以及对亚油酸和H2O2诱导的红细胞膜脂质过氧化的保护作用.结果 当归内酯对DPPH·和·OH具有良好的清除作用,其IC50分别为2.0、7.6 mg·mL-1;1、4、16 mg·mL-1的当归内酯对亚油酸的自发氧化和H2O2诱导的红细胞氧化溶血均表现出一定的抑制作用,且呈一定的量效关系.此外,各浓度梯度的当归内酯均具有一定的还原能力.结论 当归内酯具有清除自由基和抗氧化的作用.     

Pharmaceutical applications of supercritical carbon dioxide.

The appearance of a supercritical state was already observed at the beginning of the 19th century. Nevertheless, the industrial extraction of plant and other natural materials started about twenty years ago with the decaffeination of coffee. Today carbon dioxide is the most common gas for supercritical fluid extraction in food and pharmaceutical industry. Since pure supercritical carbon dioxide is a lipophilic solvent, mixtures with organic solvents, especially alcohols, are used to increase the polarity of the extraction fluid; more polar compounds can be extracted in this way. The main fields of interest are the extraction of vegetable oils from plant material in analytical and preparative scale, the preparation of essential oils for food and cosmetic industry and the isolation of substances of pharmaceutical relevance. Progress in research was made by the precise measurement of phase equilibria data by means of different methods. Apart from extraction, supercritical fluid chromatography was introduced in the field of analytics, as well as micro- and nanoparticle formation using supercritical fluids as solvent or antisolvent. This review presents pharmaceutical relevant literature of the last twenty years with special emphasis on extraction of natural materials.     

Free radical scavenging properties of pyrimidine derivatives

Free radicals are well known for playing a dual role in our body- deleterious as well as beneficial. It includes a metabolic pathway for its generation. Oxidative stress in our body occurs due to excessive generation of free radicals and reduced level of antioxidants, but at low concentrations, these radicals help to perform normal physiological functions of the body. Scientific evidence suggests that antioxidants reduce the risk for chronic diseases including cancer and heart disease. This review shows current tendency in the pyrimidine synthesis and reveals the pyrimidine core to be a very potent moiety which can be a rich source for the synthesis of new compounds having desirable antioxidant activity.     

Free radical scavenging potential of Saussarea costus

Saussurea costus (Falc.) Lipschitz from the family Asteraceae is an important medicinal drug, the roots of which are widely used in folk medicine. The antioxidant activity of the plant has been studied using its ability to scavenge DPPH, nitric oxide, superoxide radicals along with its ability to inhibit lipid peroxidation and GSH oxidation. The 1 mg mL(-1) extract had antioxidant activity with 85.2% reduction of DPPH and a 72.7% decrease in lipid peroxidation. It showed maximum inhibition of superoxide radical of 66.0%, and 58.4% inhibition of nitric oxide formation. The concentration of chlorogenic acid was 0.027% in the extract of S. costus. Thus, the therapeutic activity of the plant may be due to its antioxidant activity, probably as a result of the presence of chlorogenic acid.     

Micronization and microencapsulation of felodipine by supercritical carbon dioxide

Felodipine (FLD) is a poorly water-soluble drug. To improve its dissolution rate, the rapid expansion of supercritical solutions (RESS) technique was used to prepare micronized FLD drug particles, which were encapsulated in poly-(ethylene glycol) 4000 (PEG 4000). The physical properties of the encapsulated drug particles were characterized by a variety of analytical methods, including optical light microscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and powder X-ray diffraction (powder-XRD) and the dissolution behaviour of FLD was studied in the microparticles. The supercritical condition of micronized FLD occurred at a relatively high pressure and moderate temperature. FLD-PEG 4000 microparticles compared well with micronized FLD. RESS was effective in reducing the particle size of FLD; spot-shaped micronized FLD and popcorn-shaped FLD-PEG 4000 microparticles were observed. The particulate properties of the microparticles included a narrow distribution and uniform size. Thermodynamic analysis showed an implantation interaction between FLD and PEG 4000 molecules, but no polymorphism in the micronized FLD or FLD-PEG 4000 microparticles. FLD-PEG 4000 microparticles had a significantly faster drug dissolution rate than micronized FLD. These data show that RESS can be used to prepare FLD-PEG 4000 microparticles with small particle size (2-6 microm) and enhanced dissolution rate.     

Micronization and microencapsulation of felodipine by supercritical carbon dioxide

Felodipine (FLD) is a poorly water-soluble drug. To improve its dissolution rate, the rapid expansion of supercritical solutions (RESS) technique was used to prepare micronized FLD drug particles, which were encapsulated in poly-(ethylene glycol) 4000 (PEG 4000). The physical properties of the encapsulated drug particles were characterized by a variety of analytical methods, including optical light microscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and powder X-ray diffraction (powder-XRD) and the dissolution behaviour of FLD was studied in the microparticles. The supercritical condition of micronized FLD occurred at a relatively high pressure and moderate temperature. FLD–PEG 4000 microparticles compared well with micronized FLD. RESS was effective in reducing the particle size of FLD; spot-shaped micronized FLD and popcorn-shaped FLD–PEG 4000 microparticles were observed. The particulate properties of the microparticles included a narrow distribution and uniform size. Thermodynamic analysis showed an implantation interaction between FLD and PEG 4000 molecules, but no polymorphism in the micronized FLD or FLD–PEG 4000 microparticles. FLD–PEG 4000 microparticles had a significantly faster drug dissolution rate than micronized FLD. These data show that RESS can be used to prepare FLD–PEG 4000 microparticles with small particle size (2–6?µm) and enhanced dissolution rate.     

Micronization of drugs using supercritical carbon dioxide.

Particles from gas saturated solutions, a novel method for high pressure material processing, has been used for micronization of practically insoluble calcium-channel blockers nifedipine and felodipine and the hypolipidemic agent fenofibrate with the aim of increasing their dissolution rate and hence their bioavailability. Dependent on the pre-expansion conditions, a mean particle size of between 15 and 30 microm was achieved for micronized nifedipine and 42 microm for micronized felodipine. The particle size of processed fenofibrate, on the other hand, increased due to agglomeration. The highest dissolution rate was achieved by preparation of drug coprecipitates with PEG 4000. Copyright     

Free radical scavenging and antioxidative activity of melatonin derivatives

This article describes the synthesis and antioxidative properties of melatonin derivatives. Tryptamines and cysteinyl or mercaptopropionyl derivatives were deliberately condensed with coupling reagents to give melatonin derivatives 4a-d and 5a, b. The preliminary evaluation indicated that compound 4c showed improved scavenging activity compared with vitamin C (IC50 43 microM vs 65 microM, where IC50 is the concentration of the test compound that induced a change of 50% in absorbance during the 30 min observation) on diphenyl-p-picrylhydrazyl (DPPH) tests. Derivative 5b, which possesses the thiolactyl moiety, showed moderate potency compared with melatonin (IC50 235 microM vs 690 microM) in the H(2)O(2) scavenging test. Intriguingly, 4c displayed 2-fold more potency than melatonin (IC50 51 microM vs 125 microM) in scavenging NO in the macrophage model. These results suggested that the cysteinyl-conjugated derivative 4c may be a suitable lead to further optimize potent antioxidants for certain oxidative stress conditions.     

丹酚酸B镁盐对自由基的清除作用和对脂质过氧化的抑制作用(英文)

AIM: To study the effect of magnesium lithospermate B (MLB) on the lipid peroxidation and on its free radical scavenging activity. METHODS: MLB was incubated in rat tissue homogenate or in a free radical generating system. MLB induced inhibition of lipid peroxidation and its scavenging activity on superoxide anions and hydroxyl radicals was studied using colorimetric estimation. RESULTS: MLB inhibited the lipid peroxidation induced by either an auto-oxidant or Fe2+/VitC in vitro, in the liver homogenate, the inhibitory rate of MLB (10 mg/L) being 69.2% and 57.7%, respectively. MLB (25 and 50 mg/kg) decreased the amount of thiobarbituric acid reactive substances (TBARS) in rat serum, liver, kidney, and heart. However, it did not inhibit the lipid peroxidation of brain homogenate ex vivo. MLB scavenged superoxide anions generated from xanthine/xanthine oxidase system and iron-dependent hydroxyl radicals. CONCLUSION: MLB is an inhibitor of lipid peroxidation and scavenge superoxide anions and hydroxyl radicals both in vitro and ex vivo.     

Pharmaceutical applications of supercritical carbon dioxide

The supercritical state of a fluid is intermediate between that of gases and liquids. Supercritical fluids exhibit some solvent power which is tunable in function of pressure and temperature. In the pharmaceutical field, supercritical carbon dioxide is by far the most commonly used fluid; of course, the first applications of supercritical fluids were the replacement of organic solvents in extraction processes; other applications appeared during the last twenty years: supercritical fluids are also used as eluents in chromatography, as solvents in organic synthesis or for the processing of solid dosage forms by drug micronization, by the production of nanospheres, of solid dispersions, of porous polymeric matrices containing different active substances. Supercritical carbon dioxide has been proposed for encapsulating both hydrophilic and hydrophobic drug substances into liposomes as well as for including different active substances into cyclodextrins. There are also future prospects for the use of pressurized carbon dioxide as a sterilizing agent.     

Free radical scavenging properties of hetero-chitooligosaccharides using an ESR spectroscopy.

Nine kinds of hetero-chitooligosaccharides (hetero-COSs) with relatively higher molecular weights (90, 75 and 50-HMWCOS), medium molecular weights (90, 75 and 50-MMWCOS), and lower molecular weights (90, 75 and 50-LMWCOS) were prepared from partially deacetylated hetero-chitosans (90, 75 and 50% deacetylated chitosan), and their scavenging activities were investigated against 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, superoxide and carbon-centered radicals using electron spin resonance (ESR) spin-trapping technique. Superoxide, hydroxyl and carbon-centered radicals were generated from hypoxanthine-xanthine oxidase reaction, hydrogen peroxide-ferrous sulfate (Fenton reaction) and azo compound 2,2-azobis-(2-amidinopropane)-hydrochloride (AAPH), respectively. The ESR results revealed that 90-MMWCOS, which is having relatively medium molecular weights prepared from 90% deacetylated chitosan, showed the highest scavenging activity on all tested radicals. In addition, the radical scavenging activity of hetero-COSs increased with a dose-dependent manner, and it was dependent on their degree of deacetylation values and molecular weights.     

Free radical scavenging activity and chemical constituents of Urvillea ulmaceae

The methanol extract of Urvillea ulmaceae Kunth (Sapindaceae) aerial parts and the hexane, ethyl acetate, and hydromethanol fractions were evaluated for their free radical scavenging activity with the DPPH assay. Among all the tested fractions, the ethyl acetate fraction was the most active, exhibiting an IC₅₀ of 16.33?μg/mL, comparable to that of the commercial antioxidant BHT. Fractionation of the ethyl acetate fraction through chromatographic methods afforded trans-N-methyl-5-hydroxypipecolic acid, epicatechin, and proanthocyanidin A2 as the main constituents. Epicatechin and proanthocyanidin A2 showed potent DPPH radical scavenging activity, with IC₅₀ values of 18.34 and 11.45?μg/mL, respectively. A new compound, trans-N-methyl-5-hydroxypipecolic acid, did not show any antioxidant effect (IC₅₀?>?500?μg/mL).     

依达拉奉清除自由基机制及临床应用

研究证实,多种人类疾病的发生与机体过量自由基的产生相关,过量自由基损伤脂质,蛋白质和DNA等生物大分子,导致对机体的有害作用。依达拉奉(edaravone)为强效自由基清除剂,于2001年在日本上市,临床上主要用于治疗急性缺血性脑中风。本文对依达拉奉清除自由基的机制和治疗多种人类疾病的研究进展作简要概述,主要介绍了依达拉奉在治疗脑、心脏等多器官的缺血/再灌注损伤,肌萎缩侧索硬化症(ALS)、帕金森病(PD)、阿尔茨海默病(AD)、多发性硬化症等神经性疾病,癫痫,动脉粥样硬化,肝、肺纤维化病变,类风湿性关节炎和突发性耳聋等多种人类疾病中的应用,为进一步开发依达拉奉在临床上的新用途提供参考。     

Free radical scavenging activity of Eagle tea and their flavonoids

In this study, an online HPLC-DAD-MS coupled with 2,2′-azinobis (3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS) assay was employed for evaluating free radical scavenging activity of Eagle tea and their active components. Twenty-three chromatographic peaks were detected, and nineteen components had free radical scavenging activity. Among them, eight compounds were identified as flavonoids (hyperin, isoquercitrin, quercitrin, quercetin, kaempferol), catechins, chlorogenic acid and epicatechin based on MS data and standard chromatographic characters.     

Free radical scavenging and antiacetylcholinesterase activities of Origanum majorana L. essential oil

In the present study, Origanum majorana L. essential oil (EO) was analyzed by gas chromatography-mass spectrometry (GC-MS) and evaluated for free radical scavenging and anticholinesterase activities. GC-MS analysis revealed the presence of 4-terpineol (29.97%), γ-terpinene (15.40%), trans-sabinene hydrate (10.93), α-terpinene (6.86%), 3-cycolohexene-1-1 methanal,a,a4-trimethyl-,(S)-(CAS) (6.54%), and sabinene (3.91%) as main constituents. Origanum majorana L. EO exhibited concentration-dependent inhibitory effects on 2,2'-diphenylpicrylhydrazyl (DPPH(?)), hydroxyl radical, hydrogen peroxide, reducing power, and lipid peroxidation with IC(50) values of 58.67, 67.11, 91.25, 78.67, and 68.75 μg/mL, respectively; while the IC(50) values for the standard trolox were noted to be 23.95, 44.97, 51.30, 42.22, and 52.72 μg/mL, respectively. Interestingly, cholinesterase inhibitory activity was also found with IC(50) values of 36.40 μg/mL. We can conclude that the marjoram EO has a significant potential to be used as a natural antioxidant and anti-AChE.     

Free radical scavenging and antioxidant activities of substituted hexahydropyridoindoles. Quantitative structure-activity relationships

New synthetic substituted hexahydropyridoindoles were studied for their radical scavenging ability in a system of an ethanolic solution of alpha,alpha'-diphenyl-beta-picrylhydrazyl and for their lipid peroxidation inhibitory properties in a suspension of unilamellar dioleoylphosphatidylcholine liposomes. The activities in both in vitro systems were correlated with several structural parameters. In the homogeneous system of alpha,alpha'-diphenyl-beta-picrylhydrazyl, the sum of aromatic substitution constants (sigma(+)) and the hydration energy were shown to be effective predictors of the radical scavenging activity of the hexahydropyridoindole derivatives. Moreover, in the heterogeneous system comprising a model liposomal membrane, the overall antioxidant activity of the compounds was affected by their lipid-phase availability governed by the lipophilicity and basicity of the molecules.     

Free radical scavenging activity of 4-hydroxycoumarin derivatives]

The study of the relationships between the structure and the free radical scavenging activity of substituted 4-hydroxycoumarine derivatives, indicates the favorable effect of electron donating substituents.     

Free radical scavenging activity of red ginseng aqueous extracts

This study was performed to investigate the free radical scavenging activity of Panax red ginseng C.A. Meyer aqueous extract on 1,1-dipheny-2-picrylhydrazyl (DPPH), carbon-centered radical, hydroxyl and superoxide radicals using Electron Spin Resonance (ESR) spectrometer and spin-trapping techniques. Two different Red ginseng aqueous extracts prepared by boiling water or room temperature extraction exhibited no significant difference in free radical scavenging activity. Ginseng extracts completely eliminated DPPH radical at 2 mg/ml. About 0.5 mg/ml ginseng extracts quenched 80% carbon-centered free radicals generated from 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). Hydroxyl radical and superoxide radical were generated by UV irradiation and trapped by 5,5-dimethyl-l-pyrroline-N oxide (DMPO). Ginseng extracts scavenged 40% of hydroxyl radical at 0.1 mg/ml. Two mg/ml ginseng extracts completely scavenged superoxide radical. Ginseng extracts did not scavenge nitric oxide. The ESR data demonstrate that red ginseng aqueous extract is not a strong free radical scavenger.     

Solubility and conversion of carbamazepine polymorphs in supercritical carbon dioxide.

The aim of this work was to investigate whether mixtures of carbamazepine polymorphs could be processed in supercritical (SC) CO(2) in order to obtain the pure stable crystalline phase. To accomplish this goal the solubility of carbamazepine polymorphs I and III in supercritical CO(2) was first assessed using a low solvent flux dynamic method. Mixtures of Form I and Form III were processed in dynamic or static conditions in SC-CO(2). Differential scanning calorimetry, Fourier transformed infrared spectroscopy, and powder X-ray diffractometry were used to analyse solid samples in terms of polymorph composition. It was found that Form I and Form III of carbamazepine have different solubility in supercritical CO(2) at 55 degrees C above 300 bar. Due to the transformation of the metastable form, conversion of Form I into Form III can be carried out on a binary mixture of the two polymorphs by treating the mixture at 55 degrees C and 350 bar, under both static and dynamic conditions, via its solubilization in supercritical CO(2).     

Micronizing of steroids for pulmonary delivery by supercritical carbon dioxide

The micronization of various drugs is beset with serious problems due to the insufficient brittleness of crystals when using a jet mill. The purpose of this study was to investigate an alternative micronization technique using the aerosol solvent extraction system (ASES). Several steroids, some for systemic and some for administration by inhalation, were dissolved in an organic solvent and sprayed into supercritical carbon dioxide. The resulting particles were characterized with regard to chemical and physical properties. The following steroids were investigated: beclomethasone-17,21-dipropionate, betamethasone-17-valerate, budesonide, dexamethasone-21-acetate, flunisolide, fluticasone-17-propionate, prednisolone and triamcinolone acetonide. The spraying solution contained 1% (w/w) of drug, the solvents were dichloromethane, methanol or a mixture of both. The median particle size of the steroid particles was in most cases lower than 5 μ and consequently within the respirable range. If a surface active ingredient was added to the spraying solution the particle size increased and the contact angle decreased. HPLC-analysis showed no chemical decomposition of the drug during the process but the crystal properties of certain investigated drugs changed. This was proved by use of X-ray diffraction and scanning electron microscopy (SEM). Most of the steroids used could be micronized by means of the ASES-process with a residual dichloromethane content lower than 350 ppm in all cases.