Temporal effect of Guanxin No. 2 on cardiac function, blood viscosity and angiogenesis in rats after long-term occlusion of the left anterior descending coronary artery

AIM: Cardiac infarction is one of the main causes of death in both developing and developed countries over past decades. Currently available approaches for treating patients with this disease are not satisfactory. Traditional Chinese medicines have been increasingly paid attention to. The aim of this study was to characterize the dynamic protective effects of Guanxin No. 2 decoction (GX II) on cardiac dysfunction combined with the blood viscosity and myocardial hypertrophy parameters in myocardial infarction (MI) rats. METHODS: Male Sprague-Dawley rats (180-200 g) were randomly divided into three groups: sham-operated, coronary artery ligation (CAL), and CAL plus GX II (GX II, 10.0 g raw materials/kg/d, bid, p.o.). The experiment was carried out at 4 time points as the 3rd, 7th, 14th, and 28th day after ligation. RESULT: It was found that on the one hand, GX II could significantly improve the heart function, and remarkably decrease infarct size and inhibit ventricular remodeling. On the other hand, GX II showed some unique effects such as angiogenesis which was induced in the left ventricular tissue. This result was consistent with the finding of an augmented vascular endothelial growth factor (VEGF) expression in this area. CONCLUSIONS: The studies demonstrated that GX II exerted extensively beneficial cardioprotective effect on CAL rats, it might stimulate angiogenesis of ischemic region to compensate blood supply to the heart via upregulated VEGF expression.     

Anti-inflammatory effects of hydroalcoholic extract and two biflavonoids from Garcinia gardneriana leaves in mouse paw oedema

Garcinia gardneriana (Planch. & Triana) Zappi (Clusiaceae) is widely distributed in Brazil and used in folk medicine to treat inflammation, pain, and urinary tract and other infections. However, very few studies have analyzed these therapeutic effects. In this study, the anti-inflammatory effects of the hydroalcoholic extracts from Garcinia gardneriana (HEGG) and some of its isolated biflavonoids were evaluated. The results showed that HEGG from the leaves, bark and seeds reduced carrageenan-induced mouse paw inflammation, in addition to diminishing the myeloperoxidase activity in the stimulated tissues. The reduction of neutrophil infiltration by treatment with the HEGG from leaves was confirmed by histology. The leaf extract also reduced the paw oedema evoked by bradykinin, histamine, prostaglandin E2 and 12-O-tetradecanoylphorbol acetate. However, it partially decreased substance P and compound 48/80-caused paw oedema, without any influence on the arachidonic acid-induced oedema. Both of the isolated compounds, fukugetin and GB-2a, prevented the carrageenan-induced paw oedema. In conclusion, this study showed important anti-inflammatory effects of HEGG through its interaction with different intracellular signaling pathways, without interfering with the formation of arachidonic acid (AA) metabolites. These characteristics, in addition to the wide distribution and culturing ease of the plant, confirm its popular use and highlight its promise in the development of new anti-inflammatory drugs.     

米非司酮调控乳腺癌细胞增殖的研究

目的研究米非司酮对乳腺癌细胞系MCF-7和T47D的增殖抑制作用。方法采用四甲基偶氮唑盐(MTT)法检测米非司酮对乳腺癌细胞系MCF-7和T47D的半数抑制浓度(IC50)。不同浓度米非司酮(0.25、2.5、25和50μmol/L)分别处理人乳腺癌细胞系MCF-7和T47D1、2、3d后,观察细胞形态变化,以及检测各组细胞生长曲线。结果米非司酮对乳腺癌MCF-7和T47D细胞均有抑制作用,其抑制率均随着米非司酮浓度的增加而变化,存在明显的量效关系。通过对两种细胞抑制率(IR)值直线回归分析,米非司酮对MCF-7细胞的IC50为51.21μmol/L,对T47D细胞的IC50为54.29μmol/L。形态学观察发现,各组细胞体积变小,细胞间的链接消失,细胞内明显有黑色小颗粒聚集。25和50μmol/L浓度米非司酮对MCF-7乳腺癌细胞株生长抑制作用明显,特别是50μmol/L干预24h后在高倍镜下可见明显的核质浓缩。结论米非司酮对病理分型、激素受体型不同的乳腺癌MCF-7和T47D细胞均具有抑制增殖的作用,并呈时间和剂量依赖效应。     

Effects of a marine serine protease inhibitor on viability and morphology of Trypanosoma cruzi, the agent of Chagas disease

It has been reported that serine peptidase activities of Trypanosoma cruzi play crucial roles in parasite dissemination and host cell invasion and therefore their inhibition could affect the progress of Chagas disease. The present study investigates the interference of the Stichodactyla helianthus Kunitz-type serine protease inhibitor (ShPI-I), a 55-amino acid peptide, in T. cruzi serine peptidase activities, parasite viability, and parasite morphology. The effect of this peptide was also studied in Leishmania amazonensis promastigotes and it was proved to be a powerful inhibitor of serine proteases activities and the parasite viability. The ultrastructural alterations caused by ShPI-I included vesiculation of the flagellar pocket membrane and the appearance of a cytoplasmic vesicle that resembles an autophagic vacuole. ShPI-I, which showed itself to be an important T. cruzi serine peptidase inhibitor, reduced the parasite viability, in a dose and time dependent manner. The maximum effect of peptide on T. cruzi viability was observed when ShPI-I at 1 × 10⁻⁵ M was incubated for 24 and 48 h which killed completely both metacyclic trypomastigote and epimastigote forms. At 1 × 10⁻⁶ M ShPI-I, in the same periods of time, reduced parasite viability about 91–95% respectively. Ultrastructural analysis demonstrated the formation of concentric membranar structures especially in the cytosol, involving organelles and small vesicles. Profiles of endoplasmic reticulum were also detected, surrounding cytosolic vesicles that resembled autophagic vacuoles. These results suggest that serine peptidases are important in T. cruzi physiology since the inhibition of their activity killed parasites in vitro as well as inducing important morphological alterations. Protease inhibitors thus appear to have a potential role as anti-trypanosomatidal agents.     

Safety assessment of sandalwood oil (Santalum album L.).

Sandalwood (Santalum album L.) is a fragrant wood from which oil is derived for use in food and cosmetics. Sandalwood oil is used in the food industry as a flavor ingredient with a daily consumption of 0.0074 mg/kg. Over 100 constituents have been identified in sandalwood oil with the major constituent being alpha-santalol. Sandalwood oil and its major constituent have low acute oral and dermal toxicity in laboratory animals. Sandalwood oil was not mutagenic in spore Rec assay and was found to have anticarcinogenic, antiviral and bactericidal activity. Occasional cases of irritation or sensitization reactions to sandalwood oil in humans are reported in the literature. Although the available information on toxicity of sandalwood oil is limited, it has a long history of oral use without any reported adverse effects and is considered safe at present use levels.     

Comparative studies on the ocular and dermal irritation potential of surfactants.

Comparative studies on the irritation potential of 18 surfactants were performed using the same stock solution of surfactant for each study. The ocular irritation potential of surfactants was studied using the red blood cell test (RBC), the hen's egg test-chorioallantoic membrane (HET-CAM) and the Skinethic ocular tissue model. The skin irritation potential was assessed based on data obtained from human studies using a 24h epicutaneous patch test (ECT) and a soap chamber test (SCT). The same pH and active substance (AS) content for all surfactants tested was used depending on the test conducted. In general, clusters of substances with varying irritation potential were identified similarly by most tests. These results show that when using standardized test conditions in which pH and % AS are the same for each surfactant tested, there is a good correlation between the in vitro ocular irritation assays themselves as well as between the dermal and ocular irritation assays. In particular the RBC test seems to be not only highly predictive for ocular irritation (H(50)/DI) but also for dermal irritation and changes in barrier function (DI) induced by surfactants.     

Metabolism and transfer of the mycotoxin zearalenone in human intestinal Caco-2 cells

The mycotoxin zearalenone (ZEA) is found worldwide as contaminant in cereals and grains. It is implicated in reproductive disorders and hyperestrogenic syndromes in animals and humans exposed by food. We investigated metabolism and transfer of ZEA using the human Caco-2 cell line as a model of intestinal epithelial barrier. Cells exposed to 10–200 μM ZEA showed efficacious metabolism of the toxin. α-zearalenol and β-zearalenol were the measured preponderant metabolites (respectively 40.7 ± 3.1% and 31.9 ± 4.9% of total metabolites, after a 3 h exposure to 10 μM ZEA), whereas ZEA-glucuronide and α-zearalenol glucuronide were less produced (respectively 8.2 ± 0.9% and 19.1 ± 1.3% of total metabolites, after a 3 h exposure to 10 μM ZEA). Cell production of reduced metabolites was strongly inhibited by α-and β-hydroxysteroid dehydrogenase inhibitors, and Caco-2 cells exhibited α-hydroxysteroid dehydrogenase type II and β-hydroxysteroid dehydrogenase type I mRNA. After cell apical exposure to ZEA, α-zearalenol was preponderantly found at the basal side, whereas β-zearalenol and both glucuronides were preferentially excreted at the apical side. As α-zearalenol shows the strongest estrogenic activity, the preferential production and basal transfer of this metabolite suggests that intestinal cells may contribute to the manifestation of zearalenone adverse effects.     

Anxiolytic effect of wogonin,a benzodiazepine receptor ligand isolated from Scutellaria baicalensis Georgi

The search for novel anxiolytics devoid of undesirable side-effects typical of classical benzodiazepines (BDZs) has been intense, and flavonoids, as a relative new class of ligands, have been shown to possess anxiolytic effects in vivo. The present study evaluated the pharmacological properties of a naturally occurring monoflavonoid, 5,7-dihydroxy-8-methoxyflavone or wogonin. The affinity (K(i)) of wogonin for the benzodiazepine site (BZD-S) on the gamma-aminobutyric acid(A) (GABA(A)) receptor complex was 0.92 microM. Using electrophysiological techniques, we showed that wogonin enhanced the GABA-activated current in rat dorsal root ganglion neurons, and in Xenopus laevis oocytes expressing recombinant rat GABA(A) receptors, the enhancement was partially reversed by the co-application of a 1 microM concentration of the BZD-S antagonist anexate (Ro15-1788). Acute toxicity and behavioral effects were examined in mice. Acute lethal activity was low, with an LD(50) of 3.9 g/kg. Oral administration of wogonin (7.5 to 30 mg/kg) elicited an anxiolytic response that was similar to that elicited by diazepam in the elevated plus-maze; a dose-dependent increase in open arm entries and time spent in open arms was observed. More importantly, its anxiolytic effect was blocked by the co-administration of Ro15-1788. In the holeboard test, not only did wogonin-treated mice experience an increased number of head-dips but they also spent more time at it, showing no signs of sedation. Furthermore, wogonin did not cause myorelaxant effects in the horizontal wire test. Taken together, these data suggest that wogonin exerts its anxiolytic effect through positive allosteric modulation of the GABA(A) receptor complex via interaction at the BZD-S. Its anxiolytic effect was not accompanied by sedative and myorelaxant side-effects typical of BDZs.     

Effects of imagery motor training on torque production of ankle plantar flexor muscles

The aim of this study was to investigate in control subjects the effect of imagery training on the torque of plantar-flexor muscles of the ankle. Twenty-nine subjects were allocated to one of three groups that performed either imagery training, low-intensity strength training, or no training (only measurements). The low-intensity training served as an attention control group. Plantar-flexor torques were measured before, during, directly after, and 4 weeks after the training period. At the end of a 7-week training program, significant differences were observed between the maximal voluntary torque production of the imagery training group (136.3 +/- 21.8% of pretraining torque) vs. the low-intensity training group (112.9 +/- 29.0%; P < 0.02) and the control group (113.6 +/- 19.2%; P < 0.02). The results of this study show that imagery training of lower leg muscles significantly increased voluntary torque production of the ankle plantar-flexor muscles and that the force increase was not due to nonspecific motivational effects. Such muscle strengthening effects might be beneficial in rehabilitation for improving or maintaining muscle torque after immobilization.