In vitroantioxidant properties of dantrolene sodium

Dantrolene sodium is a skeletal muscle relaxant, which inhibits intracellular Ca2+ release from the sarcoplasmic reticulum. The aim of this study is to examine possible in vitro antioxidant effects of dantrolene sodium. For this reason, the in vitro antioxidant effects of dantrolene sodium were studied using thiocyanate methods. Additionally, the reducing power and free radical scavenging activity were determined. Dantrolene sodium showed strong antioxidant activity in the linoleic acid emulsion system. The antioxidant activity increased with an increasing amount of dantrolene sodium (50, 100, 250 microg). The 50, 100 and 250 microg samples of dantrolene sodium showed 55%, 70% and 82% inhibition on peroxidation of linoleic acid, respectively. On the other hand, the 250 microg sample of alpha-tocopherol showed 62% inhibition of peroxidation of linoleic acid. Like antioxidant activity, the reducing power of dantrolene sodium increased in a dose-dependent manner. The reducing power of dantrolene was statistically significant vs control, but lower than butylated hydroxytoluene (BHT) and quercetin. Although dantrolene sodium had free radical scavenging activity this was not statistically significant. In contrast to dantrolene sodium, quercetin and butylated hydroxyanisole (BHA) had highly potent free radical scavenging activities and those were statistically significant. According to the these results, it may be said that antioxidant effect of dantrolene sodium is more related to its antioxidant activity in linoleic acid emulsion and reducing power, than to its free radical scavenging activity. These properties may be major reasons for the inhibition of lipid peroxidation.     

Relationship between plasma concentration and effect of dantrolene sodium in man

Summary Dantrolen sodium is a muscle relaxant, which is used in the treatment of spasticity. Although it is given chronically, little is known about its pharmacokinetic behaviour. The relationship between the effect of a single oral dose of dantrolene sodium and its plasma concentration in healthy volunteers was studied by measuring the effect on the twitch tension, and in spastic patients on the decrease in muscle hypertonia. On the twitch tension dantrolene gave a depression of 49.1±9.4% (±SD) within 1.15 and 3.45 h after ingestion of 100 mg. The mean maximal plasma concentration was 1.24±0.32 µg/ml (±SD). The effect and the plasma concentration were correlated. No relationship between the plasma concentration of dantrolene sodium and its effect could be established in patients, although definite activity in 6 out of 7 patients was observed after a single oral dose of 100 mg, and plasma concentration of dantrolene sodium greater than 0.3 µg/ml were consistently associated with better results than placebo treatment in 6 out of 7 patients.     

伤痛贴的抗炎镇痛作用研究

目的研究伤痛贴的抗炎镇痛作用。方法采用大鼠角叉菜胶性足跖肿胀、小鼠琼脂肉芽肿法观察伤痛贴的抗炎作用;采用大鼠局部伤口电刺激和大鼠辐射热甩尾法观察伤痛贴的镇痛作用。结果伤痛贴能有效地对抗小鼠琼脂肉芽肿作用,抑制大鼠角叉菜胶性足跖肿胀作用,对大鼠局部伤口电刺激和辐射热甩尾法致痛均有较强的镇痛作用。结论伤痛贴具有明显的抗炎、镇痛作用。     

雷公藤内酯醇贴剂抗炎、镇痛作用研究

目的 研究雷公藤内酯醇贴剂的抗炎、镇痛作用。方法 通过小鼠耳廓肿胀、毛细血管通透性、肉芽肿以及大鼠角叉菜胶致炎实验,观察贴剂的抗炎效果;通过热板法、扭体法和电刺激法,观察贴剂的镇痛效果。结果 贴剂在雷公藤内酯醇含量为3.72,7.44,14.88 mg·m^-2内能有效抑制由二甲苯诱发的小鼠耳廓肿胀、腹部皮肤毛细血管通透性增高现象,抑制纸片引起小鼠肉芽组织增生以及角叉菜胶致大鼠足趾肿胀;并对醋酸所致小鼠腹痛扭体有抑制作用,提高鼠尾电刺激痛阈值。结论 雷公藤内酯醇贴剂对急、慢性炎症有良好抑制作用,对化学性刺激有一定镇痛效果。     

苯甲酰青藤碱的镇痛抗炎作用

目的:考察青藤碱衍生物苯甲酰青藤碱的镇痛、抗炎作用.方法:用小鼠扭体法、小鼠热板法、小鼠耳肿胀法、大鼠足跖肿胀法等试验观察.结果:苯甲酰青藤碱可抑制冰醋酸致小鼠疼痛的作用,提高小鼠热板痛阈值,抑制由二甲苯引起的小鼠耳肿胀,对角叉菜所致的足肿胀有抑制作用.结论:苯甲酰青藤碱具有镇痛、抗炎作用,且呈量效关系.     

愈伤灵膏的抗炎镇痛作用

目的研究愈伤灵膏的抗炎镇痛作用。方法采用血管通透性实验、小鼠耳肿胀实验、大鼠角叉菜胶性足跖肿胀实验、小鼠光热法及醋酸所致小鼠扭体反应等炎症、疼痛模型考察愈伤灵膏的抗炎镇痛作用。结果愈伤灵膏可明显抑制烫伤部位毛细血管通透性 ;对角叉菜胶致大鼠足肿胀和二甲苯致小鼠耳肿胀有明显的抑制作用 ;对光热致小鼠足部疼痛、醋酸致小鼠扭体均有明显的镇痛效果。结论愈伤灵膏具有明显的抗炎、镇痛药效     

溶石冲剂抗炎、镇痛、利尿作用的药效学试验

目的考察溶石冲剂在抗炎、镇痛、利尿方面的药效作用.方法抗炎作用采用小鼠耳肿胀法,镇痛作用采用醋酸扭体法,利尿作用采用大鼠代谢笼法.结果溶石冲剂高、中、低剂量能明显降低二甲苯所致小鼠耳廓肿胀度,明显抑制醋酸致小鼠的扭体反应,6h内能明显增加大鼠排尿量,与空白组比较具有显著性差异(P<0.05).结论溶石冲剂具有明显的抗炎、镇痛、利尿的作用.     

紫杉醇脂质体凝胶剂的制备及其镇痛抗炎作用

目的制备紫杉醇脂质体凝胶剂,对其镇痛抗炎作用进行初步研究。方法薄膜分散法制备紫杉醇脂质体,用透射电镜观测其形态,用激光纳米粒度仪测定粒径大小及分布,用HPLC测定其包封率。脂质体进一步制成凝胶剂后,体外透皮实验测定其不同时间的体外透皮量,考察其体外透皮情况。大鼠角叉菜胶致足肿胀模型及小鼠甲醛致痛模型,考察紫杉醇脂质体凝胶剂的镇痛抗炎作用。结果制得的紫杉醇脂质体形态规则、分布均匀,平均包封率为(73.6±0.3)%(n=3),所得凝胶呈半透明状;体外透皮实验中,紫杉醇脂质体凝胶剂符合一级动力学方程,起到较好的缓释作用。抗炎实验中,与模型组比较,各给药组在一定时间内均能显著性减轻致炎足趾的肿胀程度(P<0.05),并呈现明显的量效关系。甲醛致痛实验中,给药组与模型组比较,小鼠舔足次数明显减少(P<0.05)。结论紫杉醇脂质体凝胶具有明显镇痛抗炎作用。     

Anti-inflammatory and antinociceptive effects of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine in mice

BackgroundQUAN-0808 (6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine), a new phthalazine tetrazole derivative, was evaluated for the anti-inflammatory and analgesic effects.MethodsXylene-induced ear edema, carrageenan (Carr)-induced paw edema, and acetic acid-induced capillary permeability hyperactivity in mice were used to assess the anti-inflammatory effect; acetic acid-induced writhing and hot plate responses for the analgesic activity.ResultsIn the present study, QUAN-0808 (100, 200, 400 mg/kg) and indomethacin (Indo) significantly decreased xylene-induced ear edema by 33.3, 37.5, 46.6, and 45.1%, respectively, decreased Carr-induced paw edema at 1, 2, 4 h after Carr injection, and decreased the prostaglandin E2 (PGE2) and nitric oxide (NO) levels on the edema paw at 4 h after Carr injection; QUAN-0808 (100, 200, 400 mg/kg), and aspirin (Asp, 200 mg/kg) significantly decreased Evans blue exudation in acetic acid-induced capillary permeability hyperactivity model by 26.7, 28.7, 32.3 and 29.1%, respectively, and decreased the numbers of acetic acid-induced writhing response in 15 min by 40.4, 53.6, 66.4, and 64.5%, respectively. Morphine (10 mg/kg) significantly increased the latency of the hot plate response by 136.5,117.4,67.5, and 22.7%, respectively, at 30, 60, 90, 120 min after intraperitoneal injection of morphine; however, QUAN-0808 (100, 200 and 400 mg/kg) did not produce significantly antinociceptive effects in the hot plate test, suggesting that its antinociceptive action occurs via peripheral rather than a central-acting mechanism.ConclusionsThese results show that QUAN-0808 produced potential anti-inflammatory and peripheral antinociceptive effects, and indicated that the antinociceptive effects of QUAN-0808 were related to its anti-inflammatory activity in a dose-dependent manner. Therefore, as inflammation is a peripheral process, it is suggested that QUAN-0808 exerted peripheral effects. The peripheral effect mechanisms of QUAN-0808 may be related to a decrease in the production of PGE₂, NO, bradykinin and other inflammatory mediators.     

黄金菊药效组分中抗炎镇痛的生物效应研究

目的:探究和验证黄金菊中抗炎镇痛的药效组分,比较注射用黄金菊粉针剂与口服黄金菊药效组分在抗炎镇痛上的生物等效性。方法:通过小鼠血管通透性试验、二甲苯致小鼠耳缘肿胀、醋酸扭体和热板实验,比较黄金菊药效组分对口服组和注射组抗炎镇痛的生物等效性,确定黄金菊的抗炎镇痛药效组分。结果:小鼠血管通透性实验中,阳性组的伊文思兰含量为(4.823±0.158)μg/mL,黄金菊口服组和注射用黄金菊组分别为(6.323±0.172)μg/mL和(5.959±0.134)μg/mL,两组间比较(P>0.05),其与阳性组相比(P<0.05);二甲苯致小鼠耳缘肿胀实验中,阳性组肿胀度为(0.8125±0.5489)mg,黄金菊口服组和注射用黄金菊组分别为(1.05±0.466)mg和(1.3±1.234)mg,两组间比较(P>0.05),其与阳性组相比(P<0.05);醋酸扭体实验中,阳性组扭体次数为(33.5±2.121)次,黄金菊口服组和注射用黄金菊组分别为(35.5±3.535)次和(29±1.421)次,两组间比较(P>0.05),其与阳性组相比(P<0.05);热板实验中,阳性组的痛阈提高百分率为(56.38±1.418)%,黄金菊口服组和注射用黄金菊组分别为(64.92±2.421)%和(78.85±3.682)%,两组间比较(P>0.05),其与阳性组相比(P<0.01)。结论:黄金菊的药效组分中黄芩苷、绿原酸、荭草苷和牡荆苷可以作为黄金菊的抗炎镇痛有效组分,注射用黄金菊粉针剂与口服黄金菊的药效组分中抗炎和镇痛作用上具有生物等效性。     

Synthesis and Anti-inflammatory Evaluation of New Sulfamoylheterocarboxylic Derivatives

A series of new sulfamoylthiophene and sulfamoylpyrazole carboxylic acid derivatives was synthesized. Some of these compounds show interesting analgesic properties and significant nonsteroidal anti-inflammatory activities in several models of inflammation.     

尼美舒利解热镇痛抗炎作用比较研究

目的研究尼美舒利的解热、镇痛、抗炎作用的量效关系,比较尼美舒利3种药理作用的ED50为临床合理使用尼美舒利提供依据。方法分别采用热灭活大肠埃希菌制备家兔发热模型、冰醋酸制备小鼠疼痛模型、角叉菜胶诱发大鼠足跖肿胀模型,观察尼美舒利的解热、镇痛、抗炎作用,并计算ED。结果尼美舒利能显著降低家兔体温,减少小鼠扭体次数,明显减轻大鼠足关节肿胀程度,其解热、镇痛、抗炎作用的ED50分别为0.85～1．95,2.56,3.15～4.05mg·kg^-1,根据体表面积比例换算成人ED50分别为0．50～0.60,2.72,0.26～0.59mg·kg^-1。结论尼美舒利发挥解热、镇痛和抗炎作用的ED,n存在差异,其中解热最低。     

新癀片抗炎镇痛作用机制的蛋白组学研究

目的分析新癀片抗炎镇痛作用机制,通过蛋白组学方法寻找其作用的蛋白靶点。方法大鼠随机分成对照组、模型组、吲哚美辛(2 mg/kg)组以及新癀片23.8、47.5、95.0 mg/kg组。给药组均ig给药10 m L/kg,对照组及模型组ig给予同体积去离子水。1次/d,连续3 d。于末次给药后30 min,除对照组外,在大鼠右后足垫部sc 1%角叉菜胶0.05 m L/只致炎。在致炎前和致炎后1、2 h,记录大鼠抬足潜伏期。剖杀大鼠取肝脏,肝组织蛋白经提取、双向电泳、染色和图谱分析,确定差异表达蛋白,进行蛋白质质谱分析。结果与模型组比较,新癀片23.8、47.5、95 mg/kg组差异表达蛋白个数依次为67、71、94,其中上调个数为10、11、33,下调个数为57、60、61;新癀片95 mg/kg组与吲哚美辛(2 mg/kg)组比较,差异表达蛋白89个,其中上调27个,下调62个。共鉴定出11个差异蛋白质。与模型组比较,新癀片组均可以抑制Shank3、ANXA5、TPI、PSMA2表达,增强PAH、LZTS1表达。结论新癀片可调节的蛋白明显增多,能够抑制多种相关炎症因子和肿瘤因子,增强抗炎因子及抑癌因子的表达,为新癀片"增效"作用机制提供重要理论依据。     

白术醇提物的抗炎镇痛活性研究

目的 探讨白术醇提物的抗炎镇痛活性,为进一步研究白术抗炎镇痛的作用机制提供基础。方法 采用热板法测定白术不同剂量组小鼠的痛阈值,腹腔注射0.6%醋酸刺激致痛模型(扭体法)观察白术3个不同剂量的镇痛作用;采用二甲苯致小鼠耳廓肿胀实验和角叉菜胶致大鼠足肿胀实验观察白术3个不同剂量的抗炎作用。结果 高、中剂量的白术醇提物可显著增加小鼠的热板痛域值(P<0.01,P<0.01),减少腹腔注射醋酸引起的小鼠扭体反应次数(P<0.01,P<0.01),而白术低剂量组不能有效的提高小鼠的痛阈值(P>0.05)和减少扭体反应次数(P>0.05)。在抗炎试验中,高、中剂量的白术醇提取可显著抑制小鼠耳廓肿胀度(P＜0.01,P＜0.01),而低剂量组对小鼠耳廓肿胀抑制效果不明显(P＞0.05);高剂量组在2h后能显著抑制大鼠足跖肿胀,中剂量组(除6h时间点)与白术低剂量组(除3h时间点)在药后0.5-6h之间与模型组比较均无显著性差异(P＞0.05)。结论 白术醇提物具有较好的抗炎、镇痛作用,并且随着剂量的增大,抗炎镇痛活性增强。     

Inhalation carcinogenicity of 1,1,1-trichloroethane in rats and mice

Abstract

Carcinogenicity of 1,1,1-trichloroethane (TCE) was examined by an inhalation exposure of F344 rats and BDF1 mice of both sexes to TCE at 0, 200, 800 or 3200?ppm for 6?h/d, 5?d/week for 104 weeks. In male rats, the incidences of bronchiolo-alveolar adenomas and peritoneal mesotheliomas were significantly increased in the 800 and 3200?ppm-exposed groups, respectively. The incidence of bronchiolo-alveolar adenomas in the 3200?ppm-exposed groups exceeded the range of historical control data in the Japan Bioassay Research Center. In female rats, the tumor incidences were not increased in any organs of the TCE-exposed groups. In male mice, a significant positive trend with dose was shown for incidences of bronchiolo-alveolar carcinomas, combined incidences of bronchiolo-alveolar adenomas/carcinomas and hepatocellular adenomas. The incidence of Harderian gland adenomas was significantly increased in the 3200?ppm-exposed group, and malignant lymphomas of spleen at this highest dose exceeded the range of historical control data. In female mice, the combined incidence of bronchiolo-alveolar adenomas/carcinomas was significantly increased in the 3200?ppm-exposed group, and the incidences of hepatocellular adenomas and combined incidences of hepatocellular adenomas/carcinomas were significantly increased in the 200, 800 and 3200?ppm-exposed groups with dose dependence except the combined incidence of hepatocellular adenomas/carcinomas in the 200?ppm-exposed group. The incidences of bronchiolo-alveolar adenomas in the 3200?ppm-exposed group and combined incidences of hepatocellular adenomas/carcinomas in the 200?ppm-exposed groups exceeded the ranges of historical control data. Thus, this study provided clear evidence of inhalation carcinogenicity for TCE in both rats and mice.     

臭牡丹提取物抗炎镇痛抗过敏作用的实验研究

目的：探讨臭牡丹提取物的抗炎、镇痛、抗过敏作用。方法：以醋酸致小鼠腹腔毛细血管通透法、二甲苯致小鼠耳肿胀法观察其抗炎作用；以小鼠醋酸扭体法观察其镇痛作用；以2，4-二硝基氟苯（DNFB）致敏法观察其抗过敏作用。结果：臭牡丹提取物显著抑制小鼠腹腔毛细血管炎性渗出，抑制二甲苯所致小鼠耳廓肿胀。减少醋酸致小鼠扭体次数；并降低DNFB诱导的小鼠过敏反应。结论：臭牡丹提取物具有较好的抗炎、镇痛及抗过敏作用，与其相关的中医临床疗效相符。     

对氯芬酸的钠盐与锌盐抗炎镇痛作用比较

目的：比较双氯芬酸锌盐和钠盐的抗炎镇痛作用。方法：以等剂量的双氯芬酸钠为对照,用小鼠耳廓炎症法,大鼠足肿胀法和大鼠肉芽组织增生法对双氯芬酸锌的抗炎作用进行了比较。用热板法和扭体法对锌盐的镇痛作用进行了考察。结果：对小鼠耳廓炎症,锌盐与阴性对照组之间有显著性差异,锌盐在60min时对小鼠热板镇痛作用最强,在扭体法镇痛作用上锌盐与钠盐相当;20mg.kg^-1的剂量对大鼠足肿胀,锌盐作用强于钠盐;锌盐在抑制大鼠肉芽增生作用上明显优于阴性对照组。结论：从整体上来说,钠盐与锌盐抗炎镇痛作用相当。     

基于网络药理学对茵连痛风颗粒抗炎镇痛作用的机制研究

目的 通过网络药理学的研究方法探讨茵连痛风颗粒抗炎镇痛作用的可能作用机制。方法 利用中药系统药理学数据库与分析平台(TCMSP)收集茵连痛风颗粒主要活性成分,预测其作用靶点;利用蛋白质互作网络信息建立药物与抗炎镇痛相关靶基因之间的相互作用关系,进行KEGG与GO功能富集分析。结果 茵连痛风颗粒中与抗炎镇痛密切相关的靶点共有37个,主要包括前列腺素过氧化物合酶 2（PTGS2）、白介素-6(IL-6)、IL-10、肿瘤坏死因子（TNF）等潜在作用靶点,这些靶点的作用机制主要与调节核转录因子B信号(NF-κB) 等通路相关。结论 该研究从多维度预测了茵连痛风颗粒多靶点抗炎镇痛的作用机制,为进一步验证该制剂临床作用机制提供理论依据。     

祖师麻不同提取部位的抗炎镇痛作用研究

目的 研究祖师麻叶与祖师麻皮抗炎镇痛作用.方法 采用二甲苯所致小鼠耳肿胀和大鼠角叉菜胶足肿胀方法,研究祖师麻叶与祖师麻皮的抗炎作用;采用热板法、醋酸扭体法、光照甩尾法,研究祖师麻叶与祖师麻皮的镇痛作用.结果 祖师麻叶与祖师麻皮对小鼠耳肿胀和大鼠足肿胀均有显著的抑制作用,能明显延长热板所致的小鼠舔后肢的时间,显著减少小鼠扭体反应的次数,显著提高光电引起的痛阈值.结论祖师麻叶与祖师麻皮均具有较强的抗炎、镇痛作用,祖师麻叶作用更强.