A network pharmacology-based strategy for predicting anti-inflammatory targets of ephedra in treating asthma

Asthma, the most common chronic respiratory disease in the world, is involved in a sustained inflammatory response caused by a variety of immune cells. Ephedra with multi-target, multi-pathway functions is an effective treatment for asthma. However, the ingredients and anti-inflammatory targets of ephedra in treating asthma are unclear. Therefore, there is a need for further research. Ephedra-related and anti-inflammatory targets were found and then combined to get intersection, which represented potential anti-inflammatory targets of ephedra. Moreover, compound-anti-inflammatory target and asthma-target protein-protein interaction network were merged to get the protein-protein interaction network intersection and core genes in asthma-target protein-protein interaction network. For the anti-inflammatory targets of ephedra in treating asthma, Gene Ontology and pathway analysis were executed to confirm gene functions of ephedra in antagonizing inflammation of asthma. Finally, molecular docking, qRT-PCR, WB and ELISA were performed to assess the binding activities between the compounds and anti-inflammatory targets of ephedra in treating asthma. Critical compounds and anti-inflammatory targets of ephedra in treating asthma were identified, including quercetin, luteolin, kempferol, naringenin, beta-sitosterol, SELE, IL-2 and CXCL10. The biological processes of anti-inflammatory targets of ephedra in treating asthma were involved in immune response, inflammatory response, cell-cell signaling and response to lipopolysaccharide. Moreover, 22 pathways were obtained and we proved that critical compounds inhabited the expression of SELE, IL-2 and CXCL10 at mRNA and protein levels.     

浅谈仲景辛凉解表法

辛凉解表法虽首创于刘完素,完善于温病,但却溯源于仲景,仲景四方大青龙汤、越婢汤、麻杏石甘汤、白虎汤完整的体现了辛凉解表的思想。表热的根本在于卫气的阻滞,解表法最在意使卫气恢复流通,辛温、辛凉解表均不离辛者,以辛味发散或透达,邪气可随之出表,若单着眼于出汗者,已然失其本意。辛热开通气机,本不在发汗,汗液乃是随同郁热的开通一同从腠理而出,不同于西药单纯以发汗带出热量,而郁热并未解除。所以,纵使辛温解表,热如麻黄、桂枝也非为单纯发汗而设,乃取其辛散开通之意,汗液自蒸蒸而协同邪热一并而出。     

基于平喘生物效价的麻黄品质评价研究

目的研究37个不同产地麻黄平喘作用及其生物效价的差异。方法取豚鼠离体气管平滑肌建立平喘药效模型,按累积计量法于麦氏浴槽中加入不同质量浓度梯度(剂间距1:0.5)的麻黄水煎液,计算不同产地麻黄解痉率;按照《中国药典》2010年版二部附录XIV生物检定统计法项下"量反应平行线法"(2,2)法计算生物效价值;采用HPLC法测定麻黄药材中麻黄碱和伪麻黄碱的量;对不同产地麻黄生物效价值进行聚类分析。结果麻黄对磷酸组胺(His)引起的豚鼠离体气管平滑肌收缩有解痉作用,与麻黄对照药材相比,有20个产地的麻黄达显著水平(P0.05),麻黄解痉作用与给药质量浓度呈剂量依赖性,草麻黄与中麻黄种间解痉率无显著差异(P0.05);37个产地的麻黄药材与对照药材相比平喘效价值存在显著差异(P0.05、0.01),平喘效价值为22.35~489.04 U/g,可信限率(FL)13.15%~38.97%,效价相差近21.88倍,麻黄平喘生物效价与麻黄碱及伪麻黄碱总量之间相关不显著;采用聚类分析法能够将不同平喘生物效价值的麻黄区分开来,37份麻黄药材中有24份生物效价值高于对照药材,占麻黄样品总数的64.86%。结论平喘生物效价值可以定量评价不同产地麻黄的质量。     

HPLC测定麻黄及其制剂中3种生物碱含量

目的 建立HPLC同时测定麻黄及其制剂中3种生物碱含量。方法 以乙腈-甲醇-0.1%磷酸溶液(1.5∶4∶94.5)为流动相,同时测定麻黄、金麻杏止咳片和麻杏止咳片中3种生物碱的含量。结果 盐酸麻黄碱、盐酸伪麻黄碱、盐酸甲基麻黄碱的进样量分别为0.102 9~0.686,0.025?11~0.167 4,0.022 23~0.148 2 μg,分别与峰面积呈良好的线性关系;平均回收率分别为100.56%,97.84%和98.42%,RSD分别为0.20%、0.94%和1.31%(n=6)。结论 所建立的HPLC可通过测定3种生物碱的含量综合评价麻黄及其制剂的质量。     

The Severity of Toxic Reactions to Ephedra: Comparisons to Other Botanical Products and National Trends from 1993–2002

Objective. Ephedra is a botanical product widely used to enhance alertness, as a weight loss aide, and as a decongestant. Its reported adverse effects led the Food and Drug Administration (FDA) to ban ephedra-containing products in the United States in 2004. This study's purpose was to compare toxicity from botanical products containing ephedra to nonephedra products. Methods. The Toxic Exposure Surveillance System (TESS), a national poison center database, was utilized to determine the number and outcomes of cases involving botanical products reported from 1993–2002. Cases listing both a botanical product and any other drugs or chemicals were excluded a priori. Ten-year hazard rates (moderate outcomes + major outcomes + deaths per 1000 exposures) were used to compare botanical product categories. Results. There were 21,533 toxic exposures with definitive medical outcomes reported over the 10 yrs where a botanical product was the only substance involved. Of these, 4,306 (19.9%) had moderate or major medical outcomes and there were two deaths, for an overall hazard score of 200 per 1000 exposures. The number of ephedra reports to poison centers increased 150-fold over the 10-yr period. The hazard rate for products that contained only ephedra was 250 per 1000 exposures and 267 per 1000 exposures for products that contained ephedra and additional ingredients; whereas the hazard score for only nonephedra botanical products was 96 per 1000 exposures. The rate ratios for multibotanical products with ephedra (RR 1.33; 95% C.I. 1.27–1.40) and for single-ingredient ephedra products (RR 1.25; 95% C.I. 1.11–1.40) were both two to six times higher than those of other common botanical products. Yohimbe-containing products had the highest hazard score (417) and rate ratio (2.08; 95% C.I. 1.59–2.80). Conclusion. Ephedra-containing botanical products accounted for a significant number of toxic exposures with severe medical outcomes reported to poison centers. Hazard rate analysis suggests poison center–reported events involving ephedra-containing botanical products were much more likely to result in severe medical outcomes than those involving nonephedra-containing botanical products. These data support recommendations by policymakers that the sale of ephedra should be prohibited to protect consumers. Our data suggest that the botanical product, yohimbe, may also be associated with unacceptably high risks of toxicity and should receive close scrutiny from health policymakers.     

草麻黄化学成分的研究

目的：研究麻黄科植物草麻黄（Ephedra sinica Stapf.）草质茎的化学成分。方法：运用多种色谱方法,对草麻黄草质茎的n-正丁醇提取部位分离、纯化,并结合波谱方法鉴定其结构。结果：从提取部位分离与鉴定10种化合物,分别是l-麻黄碱（l-Ephedrine,1）,d-伪麻黄碱（d-Pseudoephedrine,2）,N-甲基麻黄碱（N-Methylephedrine,3）,苯丙醇胺（Phenylpropanolamine,4）,4-O-β-D-葡萄糖苷苯甲酸（4-O-β-D-glucopyranosi-debenzoic acid,5）,杜鹃醇-4＇-O-β-D-葡萄糖苷（Rhododendrol-4＇-O-β-D-glucopyranoside,6）,cis-丁香甙（cis-Syringin,7）,Pseudolaroside B（8）,腺苷（Adenosine,9）,黄嘌呤（Xanthine,10）。结论：从提取部位分离与鉴定的化合物7,8,9为首次从该植物分得。     

麻黄和五味子对肺纤维化大鼠肺组织病理形态的影响

目的：研究麻黄、五味子对大鼠肺纤维化病理形态的影响及其作用机制。方法：90只Wistar大鼠随机分为假手术组、模型组、氢化可的松组、麻黄组、五味子组以及麻黄＋五味子组,其中假手术组10只,其余各组均16只。采用博莱霉素A5气管滴入法建立大鼠肺纤维化模型。分别于治疗7和28d时观察各组肺组织病理切片,测量肺小动脉血管内径（inner diameter,ID）、中膜核密度（nuclear density,ND）,免疫组织化学法染色后检测微血管密度（microvessel density,MVD）。结果：7和28d时与假手术组比较,模型组肺泡炎等级明显增高（P〈0.01）。与模型组比较,7d时氢化可的松组肺泡炎等级明显降低（P〈0.05）,28d时麻黄＋五味子组、氢化可地松组肺纤维化等级明显降低（P〈0.05）。与假手术组比较,模型组大鼠ND增高,ID降低（P〈0.05）;与模型组比较,五味子组、麻黄＋五味子组、氢化可的松组ND降低（P〈0.05）,麻黄组、麻黄＋五味子组、氢化可的松组ID增高（P〈0.05）。与假手术组比较,模型组大鼠MVD显著增高（P〈0.05）;与模型组比较,麻黄＋五味子组、氢化可的松组MVD降低（P〈0.05）。结论：麻黄和五味子联合应用对肺纤维化的肺部小动脉损伤有保护作用,可抑制肺微小血管增生。五味子可降低ND,减少微血管计数,麻黄可增高ID。     

麻黄之再认识

麻黄作为传统中药材,应用历史悠久。近代对其药理作用和副作用的研究和报道颇多,引起人们的注意。就麻黄的传统功效主治、近代药理作用及副作用研究作一综述。     

基于454 ESTs的麻黄转录组研究

该研究应用454 GS FLX Titanium高通量测序技术对5年生草麻黄Ephedra sinica的草质茎进行转录组测序,共获得48 389条表达序列标签(express sequence tags,ESTs),序列平均长度为373 bp。所得序列与Gen Bank中麻黄的EST合并拼接,获得18 801条一致性序列(unigene)。通过与公共数据库中的序列进行同源性比较分析对所得转录本进行功能注释,结果表明其中56.0%(10 531条)的unigenes与其他生物的已知基因具有一定程度的同源性。进一步分析获得了19条可能参与麻黄生物碱生物合成的序列(共编码9个关键酶),97条细胞色素P450序列,以及大量转录因子序列。该研究为麻黄生物碱类化合物的生物合成研究奠定了基础,同时为麻黄转录组学的研究提供了海量数据,对于麻黄的功能基因组学研究具有重要意义。     

酸碱对药麻黄与甘草在麻杏石甘汤中的配伍化学研究

目的:考察麻黄与甘草酸碱对药在麻杏石甘汤中配伍前后麻黄碱与甘草酸提取量的变化规律.方法:采用高效液相色谱法对麻黄,甘草单味药提取液,麻黄甘草对药提取液及全方提取液中麻黄碱和甘草酸提取量进行测定.结果:各样品液中麻黄碱变化不明显,全方中甘草酸提取量较单味药及对药提取药液降低.结论:酸碱对药麻黄、甘草在配伍后麻黄碱与甘草酸基本不形成大分子复合物.