芒果树皮的化学成分研究

目的 对芒果(Mangifera indica L.)树皮的化学成分进行研究。方法 用色谱法分离,并用波谱法对化合物的结构进行鉴定。结果 从芒果树皮中分离鉴定了7个化合物,分别为芒果苷(1)、西瑞香素(2)、杨梅素(3)、杨梅苷(4)、芦丁(5)、槲皮素(6)和β-谷甾醇(7)。结论 芒果苷为芒果树皮的主要化学成分;杨梅素和杨梅苷为首次从该植物中分离得到。     

Mangifera indica L. extract (Vimang) and mangiferin reduce the airway inflammation and Th2 cytokines in murine model of allergic asthma

Objectives The aim was to study the effects of Mangifera indica extract and its major component mangiferin on lung inflammation response and Th2 cytokine production using a murine experimental model of allergic asthma. Methods BALB/c mice were intraperitoneally sensitized with 10 µg of ovoalbumin (OVA) adsorbed on aluminium hydroxide on days 0, 7 and 14. Seven days after the last injection, the mice were challenged with 2% aerosolized OVA inhalation for 30 min beginning on day 21 and continuing until day 24. To evaluate the protective effect, mice were orally treated with M. indica extract (50, 100 or 250 mg/kg) or mangiferin (50 mg/kg) from days 0 to 24. Anti‐OVA immunoglobulin E, interleukin (IL)‐4 and IL‐5 were determined by ELISA and lungs were analysed by histology. Key findings M. indica extract and mangiferin produced a marked reduction of airway inflammation around vessels and bronchi, inhibition of IL‐4 and IL‐5 cytokines in bronchoalveolar lavage fluid and lymphocyte culture supernatant, IgE levels and lymphocyte proliferation. Conclusion This is the first pre‐clinical report of the anti‐inflammatory properties of M. indica extract and mangiferin in experimental asthma and it could be an important part of pre‐clinical requirement necessary for its use to complement the treatment of this complex disease.     

In vivo acute toxicological studies of an antioxidant extract from Mangifera indica L. (Vimang)

Mango (Mangifera indica L.) stem bark aqueous extract (MSBE) is a natural product with antioxidant, anti-inflammatory, analgesic, and immunomodulatory effects. Its formulations (e.g., tablets, capsules, syrup, vaginal oval, and suppositories) are known by the brand name of Vimang®. In view of the ethnomedical, preclinical, and clinical uses of this extract and the necessity to assess its possible toxicological effect on man, a toxicological analysis of a standard extract is reported in this paper. Acute toxicity was evaluated in mice and rats by oral, dermal, and intraperitoneal (i.p.) administration. The extract, by oral or dermal administration, showed no lethality at the limit doses of 2,000 mg/kg body weight and no adverse effects were found. Deaths occurred with the i.p. administration at 200, but not 20 mg/kg in mice. MSBE was also studied on irritant tests in rabbits, and the results showed that it was nonirritating on skin, ocular, or rectal mucosa. The extract had minimal irritancy following vaginal application.     

Synergistic effect of tincture of Crataegus and Mangifera indica L. extract on hyperlipidemic and antioxidant status in atherogenic rats

This study was designed to address the synergistic effect of tincture of Crataegus (TCR) and Mangifera indica L. (MNG) extracts on the lipid and antioxidant parameters in the development of aortic lesions in diet-induced atherosclerosis in rats. TCR, is an alcoholic extract made from the berries of Hawthorn, Crataegus oxyacantha with flavanoids as the main constituent. MNG, is an alcoholic extract made from the stem bark of Mangifera indica L. with polyphenols as the main constituent. Simultaneous oral administration of these two extracts (0.5 ml/100 g body weight) to rats fed with an atherogenic (4% cholesterol, 1% cholic acid, 0.5% thiouracil) diet prevented the elevation of lipids in the serum and heart and also caused a significant decrease in lipid accumulation in the liver and aorta reverting the hyperlipidaemic condition of these rats. These extracts significantly restored the activity of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione, thereby restoring the antioxidant status of the organism to almost normal levels. This effect could be attributed to the synergistic activity of flavonoids in TCR and polyphenols of MNG.     

Vascular effects of the Mangifera indica L. extract (Vimang)

The effects of the Mangiferia indica L. (Vimang) extract, and mangiferin (a C-glucosylxanthone of Vimang) on the inducible isoforms of cyclooxygenase (cyclooxygenase-2) and nitric oxide synthase (iNOS) expression and on vasoconstrictor responses were investigated in vascular smooth muscle cells and mesenteric resistance arteries, respectively, from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Vimang (0.5-0.1 mg/ml) and mangiferin (0.025 mg/ml) inhibited the interleukin-1beta (1 ng/ml)-induced iNOS expression more in SHR than in WKY, and cyclooxygenase-2 expression more in WKY than in SHR. Vimang (0.25-1 mg/ml) reduced noradrenaline (0.1-30 microM)- and U46619 (1 nM-30 microM)- but not KCl (15-70 mM)-induced contractions. Mangiferin (0.05 mg/ml) did not affect noradrenaline-induced contraction. In conclusion, the antiinflammatory action of Vimang would be related with the inhibition of iNOS and cyclooxygenase-2 expression, but not with its effect on vasoconstrictor responses. Alterations in the regulation of both enzymes in hypertension would explain the differences observed in the Vimang effect.     

Studies on the Effect of Histamine in Isolated Human Pulmonary Arteries and Veins

Abstract: The effect of histamine (0.01–200 μM) was studied in isolated human pulmonary vessels. Histamine induced concentration dependent contractions in both arteries and veins. In veins the maximal response to histamine was lower than in arteries. Histamine and 2-methyl-histamine had a dual action in both arteries and veins clearly demonstrated in vessels precontracted with potassium. In these vessels histamine and 2-methyl-histamine induced relaxation at low concentrations and contractions at high concentrations. Veins were more sensitive to the relaxant effect of histamine than arteries. Mepyramine eliminated the dual action of 2-methyl-histamine and histamine and unveiled a mepyramine resistant relaxation at the highest histamine concentrations used which was resistant to the effect of cimetidine and metiamide. The H₂ receptor agonist dimaprit (10–400 μM) induced a slight relaxation in both arteries and veins that could be eliminated by metiamide (100 μM). The results show that histamine has a dual action in human pulmonary vessels which includes a contractile effect mediated via H₁ receptors and a relaxant response partly mediated through H₁ receptors and partly via unspecific mechanisms. However, an H₂ mediated relaxant effect cannot be excluded.     

罗氟司特和齐留通对哮喘大鼠气道平滑肌收缩功能的影响

目的 通过观察磷酸二酯酶4抑制剂罗氟司特和5-脂氧酶抑制剂齐留通对哮喘气道平滑肌收缩功能的影响,探讨罗氟司特和齐留通对气道平滑肌的药理作用。方法 取正常及哮喘大鼠的气道平滑肌条,采用乙酰胆碱（acetylcholine,Ach）梯度累积给药进行肌条收缩功能研究,并进行罗氟司特或齐留通梯度累积给药的肌条舒张功能研究,同时设置药物预孵处理,利用张力换能器和计算机生物信号采集系统观察和记录各种方式处理下其收缩功能的变化。结果 采用累积剂量给药法加入收缩剂Ach（10^-8~10^-3 mol·L^-1）后,正常大鼠和哮喘模型大鼠气道平滑肌收缩无显著性差异。由Ach诱发平滑肌条收缩达到最大程度,采用累积剂量给药法加入罗氟司特或齐留通（10^-8~10^-3 mol·L^-1）后,哮喘大鼠气道平滑肌对罗氟司特的敏感性高于正常大鼠,而对齐留通的敏感性低于正常大鼠。使用罗氟司特预孵,并采用累积给药法加入收缩剂Ach（10^-8~10^-3 mol·L^-1）,哮喘大鼠气道平滑肌和正常大鼠对Ach的反应性无明显差异,而齐留通预孵后,累积给药法加入Ach（10^-8~10^-3 mol·L^-1）,哮喘大鼠平滑肌对Ach的反应性明显高于正常健康大鼠。结论 罗氟司特能抑制哮喘气道平滑肌的收缩功能,同时不诱导气道的高反应性,而齐留通对哮喘气道平滑肌的收缩抑制作用不明显,且可能诱导气道高反应性。     

Modulation of rat macrophage function by the Mangifera indica L. extracts Vimang and mangiferin

Vimang is an aqueous extract of Mangiferia indica L., traditionally used in Cuba as an anti-inflammatory, analgesic and antioxidant. In the present study, we investigated the effects of Vimang and of mangiferin (a C-glucosylxanthone present in the extract) on rat macrophage functions including phagocytic activity and the respiratory burst. Both Vimang and mangiferin showed inhibitory effects on macrophage activity: (a) intraperitoneal doses of only 50-250 mg/kg markedly reduced the number of macrophages in peritoneal exudate following intraperitoneal injection of thioglycollate 5 days previously (though there was no significant effect on the proportion of macrophages in the peritoneal-exudate cell population); (b) in vitro concentrations of 0.1-100 microg/ml reduced the phagocytosis of yeasts cells by resident peritoneal and thioglycollate-elicited macrophages; (c) in vitro concentrations of 1-50 microg/ml reduced nitric oxide (NO) production by thioglycollate-elicited macrophages stimulated in vitro with lipopolysaccharide (LPS) and IFNgamma; and (d) in vitro concentrations of 1-50 microg/ml reduced the extracellular production of reactive oxygen species (ROS) by resident and thioglycollate-elicited macrophages stimulated in vitro with phorbol myristate acetate (PMA). These results suggest that components of Vimang, including the polyphenol mangiferin, have depressor effects on the phagocytic and ROS production activities of rat macrophages and, thus, that they may be of value in the treatment of diseases of immunopathological origin characterized by the hyperactivation of phagocytic cells such as certain autoimmune disorders.     

大鼠胸主动脉舒缩反应节段性差异的等效转换

目的: 通过相关分析消除离体动脉不同节段反应差异对实验结果的影响.方法: 以生理多道记录仪记录离体大鼠胸主动脉环从下到上4节段舒缩张力反应,用回归方程对舒缩反应节段性差异作等效转换.结果: 大鼠胸主动脉下段对苯肾上腺素收缩反应高于次下段、次上段和上段,次下段高于次上段、上段 (P<0.05);下段对乙酰胆碱舒张反应高于次下段、次上段和上段,次下段高于次上段和上段(P<0.05).相关分析显示节段间收缩反应呈直线相关;舒张反应上段对下段呈曲线相关,余呈直线相关.按相关方程等效转换各动脉节段的舒缩反应,可消除反应的节段差异(P>0.05).结论: 通过回归方程作等效转换可消除动脉舒缩反应的节段性差异.     

Effect of intravenous magnesium sulphate on airway calibre and airway reactivity to histamine in asthmatic subjects

In a randomized, double-blind, placebo controlled cross-over study we have investigated the effect of intravenous magnesium on airway calibre and airway reactivity to histamine in 20 subjects with mild to moderate asthma. After baseline measurements of forced expiratory volume in one second (FEV₁), subjects received 100 ml normal saline with or without 2 g of magnesium sulphate by infusion over 20 min. Measurements of FEV₁ were repeated at 5 min intervals throughout the infusion, and the provocative dose of histamine required to drop the FEV₁ by 20% from baseline ( PD ₂₀FEV₁) was determined at 20 min. The area under the curve (AUC) in litre minutes for change from baseline in FEV₁ between 0 and 20 min was significantly higher on the magnesium study day (mean difference in AUC (95% CI) 1.71 (0.02-3.4), P = 0.049). The increase in FEV₁ from baseline with magnesium relative to saline was maximal at 20 min (mean difference (95% CI) 0.13 (0.02-0.23) 1, P = 0.01). Log P D ₂₀FEV₁ to histamine was not significantly different after magnesium and saline (mean difference in log P D ₂₀FEV₁ (95% CI) 0.04 (-0.19 to 0.27), P = 0.7). We conclude that intravenous magnesium is a weak bronchodilator but does not alter airway reactivity at this dose in stable asthmatic subjects.     

Histamine Release Induced by Compound 48/80 from Isolated Rat Mast Cells: Dependence on Endogenous ATP

Abstract: Antimycin A (0.2 μM) reduced the ATP content in isolated rat mast cells to 25–30 % of the original value. Pyruvate (4.9 mM) did not restore the ATP content in antimycin A-treated cells, indicating a complete block of oxidative ATP production. 82–97 % of the glucose which disappeared from suspensions of mast cells in the presence of antimycin A was recovered as lactate. Therefore, the rate of lactate accumulation in suspensions of antimycin A-treated cells was used as a measure of the cellular ATP production rate. Maximal accumulation occurred with 1.1 mM glucose. Incubation with glucose (0.51 mM) for 2.5 min. completely restored the ability of mast cells pretreated with antimycin A to release histamine when exposed to compound 48/80. Concomitantly, the ATP content in the cells was restored to a steady-state level of about 75 % of the original value. 0.29 mM glucose partially restored the histamine release as well as the ATP level whereas 0.13 mM glucose did not affect either of these parameters. The turnover time of ATP at steady-state was about 30 sec. with all three concentrations of glucose, which indicates that the rate of ATP utilization by the cells is directly proportional to the ATP content. The present study supports the view that histamine release induced by compound 48/80 is dependent on the ATP content in the mast cells at the time of exposure to compound 48/80.     

苗药了哥王不同部位提取物的肾毒性研究

目的研究苗药了哥王不同部位提取物对健康大鼠的肾毒性作用,为了哥王的毒性作用机制及临床用药提供参考。方法以70%乙醇为溶剂,采用渗漉法提取,得了哥王乙醇总提取物;将上述提取物用水分散后,依次用石油醚、乙酸乙酯、正丁醇萃取得相应部位提取物,剩余为水部位提取物。将SD大鼠随机分为乙醇总提取物组、石油醚部位组、乙酸乙酯部位组、正丁醇部位组、水部位组和空白组,每组12只(雌雄各半)。给药组大鼠灌胃相应剂量的药液(乙醇总提取物317.520 mg/kg、石油醚部位7.875 mg/kg、乙酸乙酯部位78.435 mg/kg、正丁醇部位53.865 mg/kg、水部位76.545 mg/kg),每天1次,连续给药2周,再停药恢复2周;空白组大鼠灌胃等体积1.0%羧甲基纤维素钠溶液。实验期间观察大鼠的一般情况,取尿液(第14、28天)、血清和双肾组织(第15、29天),计算其肾脏指数,检测血清和尿液中的肾功能指标水平并观察肾组织的病理形态学变化。结果给药期间,与空白组比较,乙醇总提取物组、乙酸乙酯部位组大鼠出现精神萎靡、活动量和饮食量减少、大便稀薄、体质量下降等中毒行为活动特征;石油醚部位组、正丁醇部位组和水部位组大鼠精神状态较空白组稍差,活动量和饮食量稍减少,大便稀薄,体质量增长缓慢;但各组大鼠肛温无较大变化。给药2周后,乙醇总提取物组大鼠的肾脏指数,乙醇总提取物组、乙酸乙酯部位组大鼠血清中N-乙酰氨基葡萄糖苷酶(NAG)、尿素氮(BUN)、肌酐(Cr)水平,正丁醇部位组大鼠血清中NAG水平,水部位组大鼠血清中Cr水平,以及乙醇总提取物组、石油醚部位组大鼠尿液中NAG水平,乙酸乙酯部位组大鼠尿液中NAG、尿蛋白水平均显著升高(P<0.05或P<0.01);在病理形态学观察中,乙醇总提取物组、石油醚部位组和乙酸乙酯部位组大鼠有不同程度的肾小管结构不清、细胞肿胀、少数细胞坏死,伴有肾小球固缩、肾小管硬化、炎症细胞浸润。停药后,大鼠以上症状逐渐好转,精神状态有明显改善,活动量和饮食量增加,大便趋于正常。停药恢复2周后,各给药组大鼠血清和尿液中上述指标水平均恢复至与空白组接近(P>0.05);各给药组大鼠的肾小球结构逐渐恢复清晰,乙醇总提取物组、石油醚部位组和乙酸乙酯部位组大鼠少见细胞肿胀和炎症细胞浸润。结论苗药了哥王乙醇总提取物、石油醚部位和乙酸乙酯部位均具有一定的肾毒性,且具有一定的可逆性。其毒性成分可能为脂溶性成分。     

菠棱子提取液对组胺-乙酰胆碱诱发豚鼠咳喘的影响

目的观察菠棱子提取液抗动物咳喘的作用。方法幼年豚鼠随机分成4组，超声雾化法吸入不同制剂。空白对照组吸入0.9 %氯化钠溶液；低、高剂量实验组吸入100 %，200 %菠棱子提取液；阳性对照组吸入0.05 %异丙肾上腺素。各组超声雾化吸入0.01 %组胺和0.2 %乙酰胆碱诱发咳喘，观察各组动物致喘的潜伏期。结果高、低剂量实验组及阳性对照组均可延长组胺/乙酰胆碱诱发豚鼠咳喘的潜伏期，与空白对照组比较差异有极显著性(P＜0.01)。结论菠棱子提取液具有对抗组胺/乙酰胆碱诱发豚鼠咳喘作用。     

Acetylcholine Transmission in Nucleus Accumbens and VTA on Heroin- Seeking Elicited by Contextual and Conditioned Cues

The involvement of cholinergic transmission in heroin self - administration and the reinstatement of heroin - seeking was examined in rats trained to nose - poke for intravenous heroin. Systemic treatment with physostigmine modestly reduced the acquisition and rate of heroin self-administration. Following 10 -14 days of self-administration, rats were left in the home environment for 14 days. Withdrawn animals were evaluated for context-induced nosepokes during the first hour after being returned to the self-administration apparatus. One hr later a conditioned stimulus （ house light, light in the nose-poke hole, sound of the infusion pump） was presented to initiate cue-induced reinstatement.     

Effect of Trypan Blue on the Action of Acetylcholine,Histamine and Salbutamol in the Isolated Guinea-Pig Ileum

Abstract: It has been reported that trypan blue, a diazo dye with polyamphipatic structure, can inhibit the coupling of receptors to G-proteins. This inhibition of G-protein coupling has been investigated in isolated guinea-pig ileum. It was found that trypan blue could elicit a slight but dose-dependent contractile response in isolated guinea-pig ileum (4.5% of maximum contractile response induced by acetylcholine). While trypan blue potentiated the effect of histamine and shifted its dose-response curve to the left, it did not affect the contractile effects of acetylcholine. Furthermore, the relaxation which has been induced by salbutamol, a β₂ agonist, was inhibited by trypan blue. It is concluded that trypan blue, as shown in biochemical studies, act selectively and can uncouple G_s-protein from β₂ receptors. However, the effect of trypan blue on the whole tissue preparation depends on the type of G-protein involved and post G-protein processes which are stimulated after receptor activation. Trypan blue and similar agents could provide useful tools for further investigations of the mechanism of receptor-G protein coupling in the whole tissue preparation.     

Effect of Ethanol on the Pharmacokinetics of Penicillin in the Rat

Abstract: The effect of a single intraperitoneal dose of ethanol (2 g/kg) given 30. min. prior to intravenous administration of benzylpenicillin (20, 40 and 80 mg/kg) was studied in rats. Ethanol pretreated animals showed lower blood and brain tissue levels of penicillin, 15 and 30 min. after the administration of the two lower penicillin doses. This difference was not observed when the penicillin dose was raised to 80 mg/kg. The quotient between brain and serum concentrations was increased 45 min. after the injection of 20 mg/kg of penicillin. Urine collection during the following 2 days showed an increased urine volume during the first 4-hour period in animals pretreated with ethanol. During the same time period they excreted less benzylpenicillin than the controls.     

HPLC法同时测定了哥王中罗汉松脂酚和牛蒡子苷元的含量

目的建立同时测定了哥王中罗汉松脂酚和牛蒡子苷元含量的方法。方法采用HPLC法。色谱柱:依利特C18柱(200 mm×4.6 mm,5μm),流动相:甲醇-水(体积比为45∶55),流速:1.0 mL.min-1,检测波长:280 nm,柱温:30℃。结果罗汉松脂酚和牛蒡子苷元质量浓度分别在10.0~200.0(r=0.999 8)、5.00~100.0 mg.L-1(r=0.999 7)内与峰面积呈良好的线性关系,平均回收率分别为99.6%(RSD=2.3%)和100.6%(RSD=2.6%)。结论该方法适用于了哥王药材的质量控制。     

盐酸氮(艹卓)斯汀对豚鼠实验性哮喘的作用及其机理研究

目的 :观察盐酸氮 艹卓 斯汀 (azelastinehydrochlo ride ,AZ)对豚鼠实验性哮喘的作用 ,并探讨其作用机制。方法 :采用组胺和乙酰胆碱诱发在体豚鼠实验性哮喘模型 ,观察AZ的整体作用 ;采用豚鼠离体气管螺旋条 ,观察AZ对组胺所致的豚鼠离体气管螺旋条痉挛的拮抗作用。结果 :AZ能够剂量依赖性地拮抗组胺和乙酰胆碱的引喘作用 ,明显延长引喘潜伏期 ,显著减少抽搐动物发生率 ,其ED50 为 0 .2 16mg·kg-1,95 %可信限为 0 .2 14～ 0 .2 19mg·kg-1。AZ可剂量依赖性地拮抗组胺对离体气管平滑肌的收缩作用 ,使组胺量效曲线平行右移 ,其pA2 值为 8.99。结论 :预先给予AZ能显著拮抗组胺和乙酰胆碱所诱发的在体豚鼠实验性哮喘 ,抑制组胺所致的气管螺旋条收缩