Effects of Orengedoku-to and Senkanmeimoku-to, traditional herbal medicines, on the experimental elevation of aqueous flare in pigmented rabbits

We investigated the effects of Orengedoku-to (Huanglian-Jie-Du-Tang in Chinese) and Senkanmeimoku-to (Xygan-Ming-Mu-Tang in Chinese), traditional herbal medicines, on experimantal elevation of aqueous flare in pigmented rabbits. To produce the elevation of aqueous flare in rabbits, prostaglandin E2 (PGE2) was applied to the cornea with use of a glass cylinder, or lipopolysaccharides (LPS) were injected into the ear vein. Animals were pretreated by the oral administration of 150 g/day of food containing 0.7%, 0.2% or 0.07% (w/w) Orengedoku-to, or 2%, 0.6% or 0.2% (w/w) Senkanmeimoku-to for 5 days. Aqueous flare was measured with a laser flare-cell meter. Pretreatment with 0.7% or 0.2% Orengedoku-to and 2% Senkanmeimoku-to did suppress significantly (P < 0.05) elevation of aqueous flare induced by PGE2. Pretreatment with 0.7% or 0.2% Orengedoku-to and 2% or 0.6% Senkanmeimoku-to significantly suppressed (P < 0.001) elevation of aqueous flare induced by LPS. It is possible that Orengedoku-to and Senkanmeimoku-to may migrate some forms of uveitis.     

San-Huang-Xie-Xin-Tang reduces lipopolysaccharides-induced hypotension and inflammatory mediators

San-Huang-Xie-Xin-Tang (SHXT) is a traditional Chinese medicinal formula containing Coptidis rhizoma, Scutellariae radix and Rhei rhizoma. The present study aimed to determine the preventive effects of standardized SHXT on lipopolysaccharides (LPS)-induced arterial hypotension, protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), cytokines formation and prostaglandin E2 (PGE2) production. LPS-induced activation of iNOS has been recognized to increase cytokines and nitric oxide, some of them play predominant roles in sepsis. Intravenous injection of LPS (10 mg/kg) caused a marked decrease of the mean arterial pressure in normotensive rats. However, the LPS-induced arterial hypotension was inhibited by SHXT (0.01 and 0.03 g/kg), when it was given 30 min before LPS. Moreover, plasma level of cytokines and PGE2 were lowered by SHXT. In RAW 264.7 cells, SHXT (20-200 microg/ml) dose-dependently inhibited LPS (1 microg/ml)-induced iNOS and COX-2 expression, and it also significantly decreased LPS-induced cytokines in a dose-dependent manner. In conclusion, our data suggest that SHXT prevented LPS-induced arterial hypotension, which might be mediated through its inhibition activities on the expression of iNOS and COX-2, cytokines formation and PGE2 production. Therefore, its protection activity against LPS-induced arterial hypotension and inflammatory mediators release might be beneficial in the treatment of endotoxin shock and/or associated inflammation.     

不同相对截留分子量聚醚砜超滤膜精制黄连解毒汤效果的研究

目的 以黄连解毒汤(黄连、黄柏、黄芩和栀子)为研究对象,探讨采用不同相对截留分子量聚醚砜超滤膜处理后高分子物质和指标性成分变化规律以及药理作用差异,为优选黄连解毒汤超滤工艺研究提供依据.方法 逐级用pes-5w、pes-3w、pes-2w、pes-6k的超滤膜处理黄连解毒汤离心液,测定不同膜处理后渗透液和离心液中高分子物质(果胶和蛋白质)和药用指标性成分(栀子苷、黄芩苷、巴马汀和小檗碱)的质量分数及其对嗜铬细胞瘤(PC-12细胞)缺血缺氧的保护和改善作用.结果 随着膜相对截留分子量的降低.各级渗透液的高分子物质的质量分数不同程度地降低;指标性成分的质量分数除黄芩苷逐级降低外,其他都呈升高趋势;pes-3w的综合指标性成分质量分数最高;药理实验证明pes-5w渗透液对PC-12细胞缺氧缺血有很好的改善作用.结论 pes-Sw超滤膜既能有效去除非药用成分或药用性较差的物质,又能保留有效成分,适合于黄连解毒汤的精制.     

Effects of Orengedoku-to and Scutellariae radix extract on aqueous flare elevation induced by intravitreal IL-1alpha in pigmented rabbits

We investigated the effects of Orengedoku-to (huanglian-jie-du-tang in Chinese) and Scutellariae radix extract on experimental aqueous flare elevation in pigmented rabbits. To produce the elevation of aqueous flare in rabbits, interleukin-1 alpha (IL-1alpha) was injected intravitreally. Animals were pretreated with oral administration of 150 g/day of food containing 0.07%, 0.2% or 0.7% (w/w) Orengedoku-to; or 0.02%, 0.07% or 0.2% Scutellariae radix extract for 5 days. The animals were further treated with the same food for 7 days after intravitreal injection of IL-1alpha. Aqueous flare was measured with a laser flare-cell meter. Treatment with 0.2% or 0.7% Orengedoku-to and 0.07% or 0.2% Scutellariae radix extract significantly (p < 0.05) suppressed elevation of aqueous flare induced by IL-1alpha. Thus, orengedoku-to and Scutellariae radix extract have an inhibitory effect on experimental elevation of aqueous flare induced by IL-1alpha in rabbits.     

黄连解毒汤半仿生提取法提取药材组合方式的优选

目的:优选黄连解毒汤药效物质提取时方药最佳组合方式。方法:将方药排列组合成15组,用半仿生提取法提取;以小檗碱、黄芩素、栀子苷、总生物碱、总黄酮、HPLC总面积、≤1 000提取物为指标,将各指标测得值进行标准化处理,并经加权求和后得综合评价Y值,Y值大者为优。结果:7个指标综合评价Y值以AD+BC最大。结论:黄连解毒汤的提取,以黄连和栀子、黄芩和黄柏分别合提,再将提取液合并为最佳。     

黄连解毒汤及其不同配伍组方成分溶出变化研究

目的利用高效液相色谱法建立了黄连解毒汤(黄连、黄芩、黄柏、栀子)水提物的指纹图谱分析方法,结合黄连解毒汤16个全排列,评价不同配伍组方对黄连解毒汤成分溶出的影响。方法 HPLC法,反相C18柱,体积流量为1.0 mL/min,UV检测器(λ=254 nm),流动相为甲醇-水(含0.1%醋酸),梯度洗脱。结果分析、比较黄连解毒汤及其不同配伍组方的高效液相图谱,黄芩与黄连、黄柏配伍产生沉淀使生物碱溶出降低;黄芩与栀子配伍使环烯醚萜类成分溶出降低,但四药配伍溶出增加为112.6%;不同配伍组合黄酮类成分溶出增加降低不尽相同,但四药配伍增加为480.7%。结论 方法全面准确可靠,可作为黄连解毒汤体外成分分析研究的依据。     

Traditional Japanese herbal (kampo) medicines and treatment of ocular diseases: a review

Herbal medicines have been used clinically in Eastern Asia, and traditional Japanese herbal (Kampo) formulas are approved as ethical drugs. The Kampo formulas are mixtures of the crude extracts of several herbs, each of which contains multiple components. Numerous investigators have reported that some herbal medicines are efficacious for treating several human diseases. We reviewed the literature on traditional herbal medicines and treatment of ocular diseases. Oral Orengedoku-to and Kakkon-to inhibit postoperative uveitis in humans. Oral Goshajinki-gan improved ocular surface disorders in patients with type 1 diabetes mellitus. Oral Hachimijio-gan increased retinal blood flow. Keishi-bukuryo-gan Sho might be associated with vitreoretinopathy in patients with type 2 diabetes mellitus. Oral Hachimijio-gan and Goshajinki-gan delayed lens opacification in rats and mice. Oral Sairei-to, Orengedoku-to, Senkanmeimoku-to, Scutellariae radix extract, Gardeniae fructus extract, topical Liguisticum wallichii rhizoma extract, and intravenous injection of tetramethylpyrazine, baicalin, baicalein, wogonin, and crocetin inhibited some forms of experimental uveitis in rabbits. Topical glycyrrhizinate improved allergic conjunctivitis in humans and rats. Oral crocetin improved eyestrain in humans. Oral berberine diminished experimental uveitis in rats. Baicalein, wogonin, berberine, and berberrubine inhibited in vitro expression of several cytokines in cultured retinal pigment epithelial cells. Some Kampo formulas are efficacious for treating several ocular diseases in humans and animals. Some herbal extracts and their components inhibit some forms of experimental uveitis.     

SVM算法用于黄连解毒汤3种指标性成分配伍浓度与药效作用相关性的研究

目的 将支持向量机算法用于中药复方物质基础研究,探讨建立能反映黄连解毒汤中指标性成分质量浓度与药效作用相关性的数学模型.方法 根据数学组合原理,将黄连解毒汤君(黄连)、臣(黄芩)、佐(黄柏)、使(栀子)4味药组合为11组,每组分别采用膜分离、大孔吸附树脂进行分离,得到22个部位.选用鼠性肾上腺髓质嗜铬细胞瘤PC-12细胞活性跟踪筛选,MTT法测定黄连解毒汤及各分离部位对过氧化氢(H2O2)、氯化钾(KCl)、连二亚硫酸钠(Na2S2O4)诱导的PC-12细胞损伤的影响.应用支持向量机(Support Vector Machine)算法考察标识黄连解毒汤的3种指标性成分小檗碱(以盐酸小檗碱计)、黄芩苷、栀子苷量与保护率之间的相关性,寻找3种成分浓度的优化配比关系.结果 小檗碱-黄芩苷-栀子苷的浓度比为1∶13∶12时,样品对过氧化氧致细胞损伤的保护率最高;小檗碱-黄芩苷-栀子苷的浓度比为13∶1∶3时,样品对连二亚硫酸钠造模的保护率最高;而对于氯化钾造成的损伤,未能得出最优浓度.结论 不同造模机制下得到的黄连解毒汤中指标性成分的最佳浓度比不同,该汤剂中指标成分适宜的浓度范围及比例需要进一步药理实验研究确定.     

黄连上清片质量控制方法的研究

 目的建立黄连上清片有效的质量控制方法。方法采用薄层色谱法鉴别黄连、黄柏、大黄、白芷、栀子和黄芩；运用高效液相色谱法测定大黄素和大黄酚的含量。结果薄层色谱方法简便、专属性强、重复性好；含量测定结果准确，大黄素与大黄酚平均回收率分别为99.5%(RSD＝1.64%，n＝5)和97.9%(RSD＝1.32%，n＝5)。结论本方法可有效地控制黄连上清片的质量。     

交泰丸中肉桂对黄连小檗碱在大鼠体内药动学的影响

目的 考察肉桂挥发油和水提液对黄连小檗碱在大鼠体内药动学的影响.方法 将20只大鼠随机分为4组,分别灌服黄连提取物、黄连提取物加肉桂总提物、黄连提取物加肉桂挥发油、黄连提取物加肉桂水提液,采用HPLC测定大鼠血浆中小檗碱的质量浓度.结果 黄连配伍肉桂总提物后小檗碱的Cmax和AUC均明显增大,达蜂时间提前;肉桂水提液对黄连小檗碱的药动学参数影响不显著,而肉桂挥发油使小檗碱的Cmax和AUC显著增大,但增加的幅度小于肉桂总提物.结论 交泰丸中黄连、肉桂配伍,肉桂能提高黄连小檗碱的的生物利用度,其中肉桂挥发油是小檗碱药动学参数变化的影响因素之一.     

Anti-inflammatory properties of Bridelia ferruginea stem bark. Inhibition of lipopolysaccaride-induced septic shock and vascular permeability

The anti-inflammatory activity of the aqueous extract of Bridelia ferruginea stem bark was further evaluated in models which are mediated by tumour necrosis factor-alpha (TNFalpha). The effect of the extract on lipopolysaccharide (LPS)-induced septic shock was evaluated by measuring the number of deaths and the levels of serum alanine and aspartate aminotransferases following intraperitoneal injection of LPS (1 microg/kg) into D-galactosamine-primed mice. LPS-induced vascular permeability on the back skin of mice was measured by the local accumulation of Evan's blue after subcutaneous injection of LPS. Pre-treatment with Bridelia ferruginea extract (10-80 mg/kg) produced a dose-dependent inhibition of the septic shock syndrome in mice, with 80 mg/kg of the extract exhibiting comparable activity as pentoxifylline (100 mg/kg). LPS-induced dye leakage in the skin of mice was also suppressed by the extract (10-80 mg/kg). Our study suggests that one of the mechanisms of the anti-inflammatory effects of Bridelia ferruginea possibly involve the suppression of TNFalpha up-regulation.     

Aqueous garlic extract attenuates hepatitis and oxidative stress induced by galactosamine/lipoploysaccharide in rats

Injection of D-galactosamine and lipopolysaccharide (DGaIN/LPS) is useful as an experimental model of acute hepatic damage. Juvenile rats were used for investigation. The hepatoprotective activity of aqueous garlic (Allium sativum) extract (AGE) at a dose of 300 mg/kg body weight for 14 days, intraperitoneal (i.p.) prior to the induction of DGalN/LPS, was investigated against DGalN/LPS-induced hepatitis in rats. DGalN/LPS (300 mg/kg body weight/30 microg/kg body weight, i.p.), induced hepatic damage that was manifested by a significant increase in the activities of marker enzymes [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (gamma GT)], bilirubin, lipid peroxides (LPO), tumor necrosis factor (TNF-alpha) and myeloperoxidase (MPO) activity level in serum. Also, the lipid profile in serum and liver homogenate including total cholesterol, triglycerides, free fatty acids and phospholipids were significantly deteriorated. The antioxidant enzyme activities (superoxide dismutase, SOD; reduced glutathione, GSH; catalase, CAT and glutathione peroxidase, GPX) in liver homogenate were significantly decreased in the DGalN/LPS. Pretreatment of rats with AGE reversed these altered parameters near to normal control values. Results of this study revealed that AGE could afford a significant protection in the alleviation of DGalN/LPS-induced hepatic damage.     

Supercritical carbon dioxide extract exhibits enhanced antioxidant and anti-inflammatory activities of Physalis peruviana

Physalis peruviana L. (PP) is a medicinal herb widely used in folk medicine. In this study, supercritical carbon dioxide (SFE-CO2) method was employed to obtain three different PP extracts, namely SCEPP-0, SCEPP-4 and SCEPP-5. The total flavonoid and phenol concentrations, as well as antioxidant and anti-inflammatory activities of these extracts were analyzed and compared with aqueous and ethanolic PP extracts. Among all the extracts tested, SCEPP-5 demonstrated the highest total flavonoid (234.63+/-9.61 mg/g) and phenol (90.80+/-2.21 mg/g) contents. At concentrations 0.1-30 microg/ml, SCEPP-5 also demonstrated the strongest superoxide anion scavenging activity and xanthine oxidase inhibitory effect. At 30 microg/ml, SCEPP-5 significantly prevented lipopolysaccharide (LPS; 1 microg/ml)-induced cell cytotoxicity in murine macrophage (Raw 264.7) cells. At 10-50 microg/ml, it also significantly inhibited LPS-induced NO release and PGE2 formation in a dose-dependent pattern. SCEPP-5 at 30 microg/ml remarkably blocked the LPS induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Taken together, these results suggest that SCEPP-5, an extract of SFE-CO2, displayed the strongest antioxidant and anti-inflammatory activities as compared to other extracts. Its protection against LPS-induced inflammation could be through the inhibition of iNOS and COX-2 expression.     

基于网络药理学研究黄连-黄柏药对治疗溃疡性结肠炎的作用机制

目的:运用网络药理学技术研究黄连-黄柏药对治疗溃疡性结肠炎的主要活性成分,预测活性成分的作用靶点、建立"药对-活性成分-疾病-作用靶点"网络,探讨黄连-黄柏药对治疗溃疡性结肠炎的潜在作用机制.方法:运用中药系统药理学数据库与分析平台(TCMSP)筛选黄连-黄柏药对的化学成分,借助人类基因数据库获取溃疡性结肠炎的相关靶点...     

Hepatoprotective activity of Tridax procumbens against d-galactosamine/lipopolysaccharide-induced hepatitis in rats

The hepatoprotective activity of aerial parts of Tridax procumbens was investigated against d-Galactosamine/Lipopolysaccharide (d-GalN/LPS) induced hepatitis in rats. d-GalN/LPS (300 mg/kg body weight/30 microg/kg body weight)-induced hepatic damage was manifested by a significant increase in the activities of marker enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase and gamma glutamyl transferase) and bilirubin level in serum and lipids both in serum and liver. Pretreatment of rats with a chloroform insoluble fraction from ethanolic extract of Tridax procumbens reversed these altered parameters to normal values. The biochemical observations were supplemented by histopathological examination of liver sections. Results of this study revealed that Tridax procumbens could afford a significant protection in the alleviation of d-GalN/LPS-induced hepatocellular injury.     

The pharmacological effects of an aqueous extract from Acacia nilotica seeds

An aqueous extract of the seed of Acacia nilotica was investigated for its pharmacological profile. On the isolated guinea-pig ileum, the extract displayed sustained dose-related contractile activity. The contractions which were reduced by hexamethonium, promethazine or atropine were completely abolished by nifedipine. The intravenous (i.v.) administration of the extract (11, 22, 44, 55 microg/kg) to anaesthetized cats produced a dose-related significant elevation of blood pressure. The mechanisms of the spasmogenic and vasoconstrictor actions of the extract have not been determined, however, the results suggest the involvement of calcium.     

黄连及黄连解毒汤对小鼠的急性毒性实验研究

 目的 探讨黄连单味药及其复方黄连解毒汤对小鼠的急性毒性,摸索半数致死量（LD₅₀）或最大耐受量,并确定其毒性靶器官。方法 采用灌胃给药的方法,给予不同剂量黄连水煎液或黄连解毒汤水煎液,连续观察7 d,检测药物对小鼠的急性毒性作用,用加权回归几率法（Bliss）计算LD₅₀,对死亡小鼠进行主要脏器的病理学观察。结果 黄连水煎液的小鼠LD₅₀剂量（以含黄连生药量计）为18.826 g·kg-1,95%可信限为16.923~21.314 g·kg-1,LD₅为12.407 g·kg-1,LD₉₅为28.565 g·kg-1。病理结果提示,黄连对小鼠的主要毒性靶器官为脑、肝、脾、肺、肾。黄连解毒汤未引起小鼠死亡,其最大耐受量（以含黄连生药量计,黄连-黄芩-黄柏-栀子=20∶6∶6∶9）为80 g·kg-1。结论 单味黄连水煎液具有毒性,其小鼠LD₅₀剂量（以含黄连生药量计）为18.826 g·kg-1,毒性靶器官为脑、肝、脾、肺、肾;经配伍后的黄连解毒汤则较为安全。     

栀子对大鼠肝毒性的实验研究

目的：探讨栀子不同化学部位的肝毒性作用。方法：灌胃给药3 d后,观察大鼠外观、行为及体重变化；称量肝脏重并计算肝指数；测定大鼠血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）活性及总胆红素（TBIL）含量；对肝脏组织进行光镜的病理学观察。结果：3.08 g·kg^-11的水提物、1.62 g·kg^-1的醇提物、0.28 g·kg^-1的栀子苷导致肝重增加,肝指数增大,与空白比较P<0.05,P<0.001；ALT,AST活性增高,TBIL含量增加,与空白比较P<0.05,P<0.001；光镜下可见明显的肝细胞肿胀、坏死,大量炎症细胞浸润等形态改变。结论：栀子水提物、醇提物、栀子苷具有肝毒性,栀子苷是栀子肝毒性的主要物质基础。