A microdialysis study on the mechanism of action of gabapentin

To gain insight into the mechanism of action of the anti-epileptic, gabapentin, the effects of gabapentin on the in vivo extracellular gamma-aminobutyric acid (GABA) levels in the rat substantia nigra reticulata were studied using microdialysis. In order to investigate possible interference with different GABA-ergic compartments in the substantia nigra reticulata, we studied the effects of gabapentin under basal, K(+)-, nipecotic acid- and glutamate-stimulated conditions. Intraperitoneally (i.p.) administered gabapentin, at a dose of 100 mg/kg, did not significantly affect extracellular GABA levels under any condition. Thus, our data do not support the involvement of nigral GABA release in the mechanism of action of the anti-epileptic gabapentin.     

甘草次酸阳离子脂质体的制备及稳定性考察

目的:制备甘草次酸阳离子脂质体,并研究其稳定性。方法:用乙醇注入法制备甘草次酸阳离子脂质体。考察其粒径、包封率、过氧化值、在血浆中的稳定性和放样稳定性等性质。结果:所得脂质体的粒径小而均匀,呈球形和类球形,包封率为(91.6±1.2)%;离心加速试验结果显示脂质体的稳定性参数KE值较小,脂质体在血浆中释放缓慢,在4℃下放置6个月,其外观、包封率、粒径等各项指标无明显改变。结论:制得的甘草次酸脂质体包封率较高,稳定性良好。     

甘草次酸醇质体的制备研究

目的优选甘草次酸(GA)醇质体的最佳制备工艺。方法乙醇注入法制备GA醇质体,以包封率为评价指标,采用正交设计实验确定GA醇质体的最佳制备工艺。结果确定GA醇质体最佳制备工艺为:含GA0.5g的100mLGA醇质体中无水乙醇投入35mL,大豆磷脂3.0g,胆固醇0.2g。所制得的醇质体平均包封率为70.6%。结论以乙醇注入法制备的GA醇质体,包封率高、稳定。     

5种甘草次酸衍生物的制备

目的合成制备5种甘草次酸类衍生物,并对其制备工艺进行优化。方法以18β-甘草次酸为原料,分别通过高温碱催化构型转化反应以及硫酸催化酯化反应,合成制备5种甘草次酸类衍生物;利用简单的因素分析法,对5种衍生物的制备工艺进行优化;利用光谱分析法进行结构鉴定。结果通过以上方法分别制得:18β-甘草次酸的光学异构体18α-甘草次酸(产率63%),3-乙酰-18β-甘草次酸(96%),3-乙酰-18α-甘草次酸(90%),18β-甘草次酸甲酯(79%)和18α-甘草次酸甲酯(67%);对各衍生物的理化性质和光谱特征进行详细描述。结论该研究中的制备方法操作工艺简单、原料易得、产率较高,对文献工艺做了一定改进。该研究结果为甘草次酸的深入研究奠定一定基础。     

甘草次酸的差向异构体对顺铂诱导H9c2心肌细胞损伤的保护机制

目的 探究甘草次酸（GA）的差向异构体18α-GA和18β-GA对顺铂（CDDP）诱导H9c2心肌细胞损伤的保护机制。方法 采用CCK-8法检测细胞活力,筛选CDDP诱导细胞损伤的浓度,18α-GA和18β-GA安全浓度以及18α-GA与18β-GA改善CDDP致心肌细胞活力下降的有效浓度;将细胞分为对照组、CDDP组、18α-GA组和18β-GA组,使用Hoechst染色检测各组细胞凋亡情况;流式细胞术检测活性氧（ROS）水平;Mito-Tracker Red CMXRos染色评估线粒体活性;Western blot法检测各组细胞剪切化胱天蛋白酶3(C-Caspase3)、B-淋巴细胞瘤基因-2(Bcl-2)、Bcl-2相关X蛋白（Bax）以及细胞色素C(Cyt-c)的蛋白表达。结果 CCK-8实验结果显示,CDDP在20μmol/L时可使H9c2心肌细胞活力显著下降（P<0.01）;18α-GA和18β-GA浓度小于100μmol/L时,对心肌细胞无明显影响,且50和100μmol/L时均可改善CDDP导致的心肌细胞活力的降低（P<0.01）。与对照组相比,CDDP组细...     

Effect of glycyrrhetinic acid on histamine synthesis and release

The effect of glycyrrhetinic acid (18β-glycyrrhetinic acid, GA) on histarnine synthesis and release was investigated in cocultured mast cells with Swiss 3T3 fibroblasts. GA has strong dose dependent inhibitory activity for histamine synthesis and release in cocultured mast cells. GA (50 μM) inhibited about 85% of histidine decarboxylase (HDC) activity. The appearance of cells staining positively with berberine sulfate was also decreased in the presence of GA. It indicates that transdifferentiation of cultured mast cells (CMCs) was also inhibited.     

On the mechanism of action of valproid acid]

In mice, the influence of valproic acid (di-n-propylacetate, DPA) on central level of gamma-aminobutyric acid (GABA) as well as the activity of the enzymes regulating GABA metabolism, glutamate decarboxylase (GAD) and GABA-alpha-oxoglutarate aminotransferase (GABA-T) were studied. It was shown that the elevation of GABA by DPA was accompanied by an activation of GAD. GABA-T was inhibited only by toxic doses or high concentrations of DPA in vivo and in vitro, and so was GAD. DPA proved able to antagonize the biochemical alterations induced by convulsant doses of isoniazid, i.e., decreases in the level of GABA and the activity of GAD. These results point to a role of the transmitter pool of GABA regulated by GAD in the anticonvulsant effect of DPA.     

pH对甘草次酸经皮渗透性的影响

目的考察介质的pH对甘草次酸经皮渗透性的影响。方法采用HPLC法测定甘草次酸在不同pH介质中的饱和溶解度,采用摇瓶法测定其在不同pH正辛醇/PBS缓冲液中的表观油水分配系数,采用体外Franz扩散池法考察不同pH的甘草次酸饱和溶液在离体小鼠皮上的经皮渗透性。结果 pH5.0～10.8时,甘草次酸饱和溶液的稳态透皮速率随pH升高而增大,而表观渗透系数随pH升高而减小。结论甘草次酸在介质中饱和时,可通过调节pH来改善甘草次酸的稳态透皮速率。     

Effects of glycyrrhetinic acid on aminonucleoside nephrosis in rats

The effects of glycyrrhetinic acid (GA), an aglycon of glycyrrhizin extracted from the roots of Glycyrrhizae radix, on puromycin aminonucleoside (PA) nephrosis were studied in rats. Urine protein excretion in female rats (130g–150g) receiving PA (50 mg/kg) alone was significantly elevated on the 2nd day after injection of PA and reached a peak on the 14th day. Urinary protein on the 14th day was reduced to 74% in animals treated with GA (20 mg/kg) starting on the 2nd day after injection of PA. The increase in serum cholesterol and the decrease in serum protein were also suppressed by GA. Observation by electron microscopy revealed that the degree of abnormality in glomerular epithelial cells, i.e. loss or fusion of foot processes, was lower in the rats treated with GA after PA injection than in the rat treated with PA alone. Moreover, pretreatment with GA did not suppress urinary protein excretion but when it was given at the same time as PA and after PA a significant decrease in urinary protein excretion was observed. Correspondence to: H. Abe at the above address     

Electrophysiological study of the mechanism of mexidol action

It has been found that mexidol (5 mM) significantly (96 +/- 2%) depressed excitatory postsynaptic current caused by step depolarization in neurons of medial vestibular nucleus of medulla oblongata slices in young (aged 13 - 17 days) male albino rats. In addition, mexidol (2,5 - 5 mM) depressed by 94 +/- 3% excitatory postsynaptic current caused by Shaffer collaterals stimulation of CA1 pyramidal neurons of hippocampal slices in young rats. Complex MK-801 (non-competitive antagonist of NMDA receptors), in contrast to CNQX (competitive AMPA receptor antagonist), considerably decreased the depressant effect of the drug in both brain structures. Therefore, the central favorable effect of mexidol can be mediated by ion mechanisms with glutamate- and GABA-ergic components, primarily by the inhibition of ion currents through NMDA receptor complex.     

Effect of glycyrrhetinic acid on the cyclic nucleotide system of the rat stomach

Glycyrrhetinic acid (carbenoxolone) inhibited cyclic nucleotide phosphodiesterase (PDE) activity in a number of tissues from rat, guinea pig and dog. In the fundic mucosa, it was more active when cyclic AMP rather than cyclic GMP was used as substrate in the PDE assays. Glycyrrhetinic acid also raised the intracellular levels of cyclic AMP in rat pyloric and fundic mucosae in vivo with little effect on cyclic GMP levels. This effect, at least in the rat, was apparently mediated via PDE-inhibition, since the drug did not affect adenylyl cyclase activity from either mucosa. Studies with theophylline and papaverine, in addition to glycyrrhetinic acid, suggested that the effects of PDE inhibitors on gastric acid secretion could be related to their relative activities on cyclic AMP-PDE's or cyclic GMP-PDE's, owing to the possibly opposite effects mediated by the two cyclic nucleotides on acid secretion by the stomach.