Background: Alzheimer's disease (AD) is a neurological disorder. There is a considerable unmet medical need among those suffering from it. Hypothesis and purpose: Given the link between type-2 diabetes mellitus (T2DM) and AD, hypoglycemic traditional Chinese medicine formulas (TCMFs) may be a treatment for AD. We investigated the possibility of identifying anti-AD medicines in hypoglycemic TCMFs and presented another option for the screening of AD medications. Study design and methods: Paralysis of the transgenic Caenorhabditis elegans (C. elegans) strain CL4176 (caused by amyloid beta (AO)1-42 aggregates) was used to evaluate the anti-AD effect. The toxicity and neurodegeneration induced by neuronal expression of AO in the transgenic C. elegans strain CL2355 were determined using a 5-hydroxytryptamine (5-HT) assay. The transgenic AO-expressing strain CL 2006 and transgenic tau-expressing strain BR5270 were used to explore the effect of TCMFs on protein expression in C. elegans using ELISAs. Then, network pharmacology was used to determine the mechanism of action. The Traditional Chinese Medicine Inheritance Support System platform was used to investigate prescription patterns, core drugs, and optimum combinations of hypoglycemic TCMFs for AD. Results: Sixteen hypoglycemic TCMFs prolonged the PT50 (half paralysis time) of the CL4176 strain of C. elegans, reduced the percentage of worms paralyzed. The results of network pharmacology showed that prostaglandinendoperoxide synthase 2 (PTGS2) and acetylcholine esterase (AChE) are main targets of hypoglycemic TCMFs. Enriched pathway analysis showed that the cholinergic receptor-related pathway was the core pathway of hypoglycemic TCMFs. According to the "four qi and five flavors" system of TCM theory, the main pharmacological qualities were "cold" and "sweet." Through the analysis by TCMISS, we found that Huangqi-Gegen drug pair as the significant Chinese herbs of hypoglycemic TCMFs. The Huangqi-Gegen pairing had the most robust therapeutic effect when delivered at a 2:1 (v/v) ratio. It reduced the paralysis caused by 5-HT, decreased protein expression of AChE and PTGS2, and reduced AO deposition in the brain of the CL2006 strain of C. elegans.

阿霉素属蒽环类抗生素,作为广谱抗肿瘤药,广泛应用于临床.但阿霉素具有剂量依赖性,并呈现出明显的心脏毒性,使得临床应用受到限制.目前针对阿霉素致心脏毒性的作用机制尚未完全阐明,减少心脏毒性提高临床应用范围,成为近几年研究的热点.本文从阿霉素的心脏毒性机制、中药防治阿霉素心脏毒性两个方面进行综述,以期为阿霉素联合应用提供参考.

探讨7味药食同源中药水提取物及其联用对大肠杆菌、金黄色葡萄球菌、白色念珠菌的体外抑菌效果,并将其应用于抑菌喷雾剂.采用水提法提取药液,用纸片扩散法测得单药最低抑菌浓度(MIC)及最小杀菌浓度(MBC),同时以"棋盘法+中药互配"筛选对上述致病菌具有较强协同抑制作用的药物组合,并确定适宜的药物配伍制备抑菌喷雾剂.结果显示,7味药食同源中药对3种供试病原菌均具有不同程度的抑菌效果,五味子、金银花、牡丹皮、肉桂、白芍和山楂的抑菌作用较强,其对大肠杆菌的抑菌圈直径为12.50～26.50 mm,最低抑菌浓度(MIC)＜250.00 mg/mL,最小杀菌浓度(MBC)＜500.00 mg/mL;其中,五味子的抑菌作用最显著,对大肠杆菌、金黄色葡萄球菌、白色念珠菌的MIC分别为31.25 mg/mL、15.62 mg/mL、250.00 mg/mL.互配试验结果表明,10种不同的药物组合对3种供试菌的联合抑菌作用各不相同,牡丹皮和肉桂的配伍组合对大肠杆菌以及肉桂和五味子的配伍组合对金黄色葡萄球菌的联合抑菌指数(FICI)均≤0.50,表现为协同作用,其中肉桂和白芍、牡丹皮和白芍的配伍组合对致病菌也有协同或相加作用.因此,选择牡丹皮、肉桂、五味子、白芍4味药食同源中药制备抑菌喷雾剂.同时初步确定药食同源中药抑菌喷雾制剂的制备工艺流程为在40℃水浴中,向中药提取液中依次搅拌加入0.2％苯甲酸、1.0％吐温-80和5.0％1,2-丙二醇.多种药食同源中药具有抗菌作用,且合理的配伍可以产生协同增效的效果,为无毒副作用抗菌喷雾剂的开发奠定了基础.

目的 探究五倍子、黄芩、金银花、板蓝根、连翘、薄荷、山楂七味中药及其组方的抑菌作用.方法 使用水煎煮法提取各单味中药及其组方的活性成分;采用琼脂平板打孔法、纸片扩散法和平板培养法测定其抑菌圈直径、最小抑菌浓度(MIC)和最小杀菌浓度(MBC);设计7因素2水平的正交试验,初步确定最优抑菌配比.选择对抑菌活性影响最小的脱色方法.结果 7味中药中五倍子对金黄色葡萄球菌的抑菌作用最强,抑菌圈直径(30.3±0.81)mm;山楂对大肠埃希菌的抑菌作用最强,抑菌圈直径(17.7±1.03)mm;黄芩对白色念珠菌的抑菌作用最强,其抑菌圈直径为(14.5±1.38)mm.正交试验结果表明,连翘、山楂、板蓝根、五倍子、金银花、黄芩、薄荷按质量比为2:1:2:2:1:2:1组成的中药组合物抑菌效果最好.75％水提醇沉法脱色对抑菌作用影响小.结论 五倍子、山楂和黄芩分别对金黄色葡萄球菌、大肠埃希菌、白色念珠菌的抑菌作用最强,7味中药的配伍可以产生协同增效的效果,可使用75％水提醇沉法对药液脱色.

目的:建立LPS(脂多糖)诱导的急性肺损伤小鼠模型,探究麻杏石甘汤对急性肺损伤的保护作用及机制.方法:将C57BL/6雄性小鼠随机分为正常对照组、模型对照组、麻杏石甘汤5.4、54、108 g/kg组和哌非尼酮200 mg/kg组,每组10只,连续灌胃给予相应药物或去离子水7 d,第8 d注射LPS建立急性肺损伤模型,从肺功能检测、肺部CT检测、脏器指数、肺组织病理学检查、肺组织湿/干质量比(W/D)、血清及肺灌注洗液(BLAF)中肿瘤坏死因子α(TNF-α)、白介素1 β(IL-1 β)、IL-6含量测定、肺组织氧化应激指标变化等综合探讨麻杏石甘汤对LPS诱导的急性肺损伤小鼠的保护作用机制.结果:与正常对照组比较,模型对照组肺灌洗液和血清中TNF-α、IL-1 β、IL-6含量,肺组织病理学产生变化,肺功能指标明显改变、CT异常、肺指数显著增加,炎症因子明显增加,氧化指标明显异常,成功建立急性肺损伤模型(P＜O.05或P＜0.01);麻杏石甘汤能明显或部分改善模型小鼠肺部炎性细胞浸润,改善肺功能和肺部CT,能明显降低LPS诱导的急性肺损伤模型小鼠中肺组织的丙二醛(MDA)的含量,同时也能增强急性肺损伤小鼠肺组织中的超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)的活力,还能降低血清和BLAF中IL-1 β、IL-6以及TNF-α等细胞炎症因子的含量,下调肺组织p38MAPK、JNK、ERK1/2、TNF-α、IL-6蛋白的表达(P＜0.05或P＜0.01).结论:麻杏石甘汤可能通过抗氧化应激、抑制相关炎症因子、调节炎症MAPK/NF-kB通路等多种途径有效预防急性肺损伤.

KRAS is a biomarker for non-small cell lung cancer-targeted therapy, but there is currently no effective KRAS-targeting medication. Realgar is an impelling anti-cancer drug, however its significance in KRAS mutant lung cancer is uncertain. According to our findings, the IC50 of H23 (KRAS mutant) cells is 2.99 times lower than that of H1650 (non-KRAS mutant) cells. Flow cytometry and the Hoechst 33258 staining assay revealed that H1650 cells treated with 4 µg/ml realgar had an apoptotic rate of 8.2%, while H23 cells had a rate of 21.46%. Accordingly, realgar was more sensitive to KRAS mutant cells. Transcriptome sequencing test indicated that there were 481 different expression genes in H23 cells treated with realgar. In H23 cells treated with realgar, mitochondria shrank, inner membrane folding was disturbed, and mitochondrial membrane potential crushed. Realgar boosted intracellular Fe2+, reactive oxygen species, malondialdehyde and glutathione levels, which were all reversed by ferroptosis inhibitor Fer-1. Realgar decreased phosphorylated p-Raf, p-ERK1/2 and increased p-p38 and p-JNK, whereas only p-Raf was abolished by Fer-1. Raf inhibitor Sorafenib accelerated the realgar-induced ferroptosis. On H23 cells treated with realgar, the expression of GPX4, SCL7A11 decreased while ACSL4 expression increased; this effect could also be amplified by Sorafenib. In conclusion, the present study indicated that realgar may induce ferroptosis by regulating the Raf, and hence plays a role in anti-KRAS mutant lung cancer.

目的 探究五倍子、黄芩、金银花、板蓝根、连翘、薄荷和山楂7味"药食同源"中药及其组方在大肠杆菌、金黄色葡萄球菌及白色念珠菌中的抑菌作用,筛选"药食同源"中药组方的最佳配比并初步确定该中药组方的脱色方法.方法 使用水煎煮法提取各单味中药及其组方的活性成分,采用琼脂平板打孔法、纸片扩散法和平板培养法测定其抑菌圈直径、最小抑菌浓度(MIC)和最小杀菌浓度(MBC);设计7因素2水平的正交试验,采用抑菌圈的直径作为评判指标初步确定最优抑菌配比.以最佳配方水提液为原料,用活性炭吸附法、大孔树脂脱色法、H2O2氧化脱色法及水提醇沉法4种方法对其脱色效果进行综合评价.以脱色后药液的气味及颜色变化,以3种供试菌的抑菌圈直径和MIC等作为评价指标.结果 7味中药对3种供试病原菌均具有不同程度的抑菌效果,五倍子、黄芩、金银花和山楂对大肠杆菌和金黄色葡萄球菌的抑菌作用较强,其抑菌圈直径达到14.5～30.3 mm,MIC<250 g·L-1,MBC<500 g·L-1,且对白色念珠菌也有一定的抑制作用;板蓝根、连翘和薄荷对3种供试菌的抑菌效抑菌活性很弱甚至无抑菌效果.正交试验结果表明,7味不同配比的中药组合对大肠杆菌、金黄色葡萄球菌的联合抑菌作用具有协同作用.由连翘、山楂、板蓝根、五倍子、金银花、黄芩和薄荷的质量比为2:1:2:2:1:2:1组成的中药组合物对大肠杆菌和金黄色葡萄球菌的MIC为1.95和3.90 g·L-1;MBC为7.81和31.25 g·L-1,在增强抑菌效果的同时又降低了MIC和MBC;脱色结果表明75％水提醇沉法对药液的脱色效果最佳.结论 多种"药食同源"中药具有抗菌作用,且其合理的配伍可以产生协同增效的效果,这将为无毒副作用和无刺激性抗菌剂的开发奠定了基础.

目的 运用网络药理学方法分析荆防败毒散治疗儿童新型冠状病毒肺炎(COVID-19)的可能作用机制.方法 通过中药系统药理学数据库与分析平台(TCMSP)和中药分子机制的生物信息学在线分析工具(BATMAN-TCM),筛选荆防败毒散各中药的主要化学成分及靶点;采用GeneCards、NCBI、CTD及OMIM数据库检索COVID-19相关靶点;通过STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络;采用Omic-share平台对共有靶点进行基因本体(GO)及京都基因与基因组百科全书(KEGG)分析;检索多脏器损伤、免疫损伤的疾病靶点,将荆防败毒散与之做映射,计算交集靶点占荆防败毒散靶点的百分比.结果 荆防败毒散由12味中药组成,包含599个化合物,相对应的靶点有2290个.荆防败毒散的靶点与COVID-19有12个相同的炎症因子,每个炎症因子对应多个化合物.荆防败毒散与COVID-19有166个交集靶点,40个关键靶点.KEGG信号通路富集分析得到152条信号通路(P＜0.05);GO分析得到生物过程结果有1906个,细胞组成有32个,分子功能有73个(P＜0.05).荆防败毒散与各脏器损伤靶点和免疫损伤靶点的共有靶点较多,且共有靶点占疾病靶点的百分比均高于20％.结论 荆防败毒散可能通过抗炎、保护脏器损伤、免疫调节等作用治疗COVID-19.

目的 探讨SIRT1/FOXO1通路在三氧化二砷(ATO)诱导的心脏毒性机制,以及黄芪甘草汤的防护作用.方法 以ATO 5 mg·L-1诱导H9c2细胞损伤模型,采用MTT法、流式细胞术测定不同浓度黄芪甘草汤对心肌细胞存活率、凋亡率以及ROS的影响;Western印迹法测定细胞中SIRT1,FOXO1,Akt和P53的蛋白表达.结果 不同浓度的ATO作用于H9c2细胞24 h后,细胞存活抑制率呈浓度依赖性.ATO处理后心肌细胞凋亡率和ROS水平显著升高,SIRT1显著降低,FOXO1水平显著升高(P<0.05),而加入黄芪甘草汤后均发生逆转.ATO增强EX257对SIRT1的抑制作用,说明ATO引起的心脏毒性部分是通过SIRT1介导.结论 ATO引起的心脏毒性与SIRT1密切相关,并且黄芪甘草汤可防治ATO引起的心肌细胞氧化应激与凋亡,该过程可能与SIRT1/FOXO1通路密切相关,为黄芪甘草汤联合ATO用药的开发及临床应用提供理论依据.

目的 阿尔茨海默病(AD)是世界第一的神经退行性疾病,目前缺乏有效的治疗药物.研究发现,AD与2型糖尿病(T2DM)之间存在密切联系.课题组系统分析了19种糖尿病治疗复方,从中筛选出具有AD治疗作用的黄芪葛根汤,并通过网络药理学以及现代药理学基础分析探讨黄芪葛根汤治疗AD的潜在靶点及信号通路,阐述其可能的作用机制.方法 采用Aβ1-42基因诱导的秀丽隐杆线虫作为AD病理模型,探讨黄芪葛根汤的抗AD作用.从TCMSP和BATMAN-TCM数据库搜索黄芪葛根汤中2味中药的化合物及靶点,使用GeneCards、NCBI、CTD以及OMIM数据库检索AD和T2DM的靶点;通过STRING数据库构建蛋白质相互作用网络;通过cytoHubba,选择MCC对关键靶点进行分析;采用Metascape数据库对关键靶点进行聚类分析;采用Omicshare平台对关键靶点进行KEGG分析及GO分析,以获取潜在靶标与机制.结果 黄芪葛根汤共包含2味中药,14种化合物,相对应的药物靶标有113个,黄芪葛根汤、AD、T2DM共同交集靶点共31个.对交集靶点进行MCC聚类分析获得JUN,PTGS2和SIRT1等核心靶点.交集靶点可以聚类为3类,分别与过氧化物酶体增殖剂激活受体信号传导途径、发育生长和凋亡信号通路有关,这些途径和AD密切相关.通过KEGG信号通路富集筛选所得排名前三的信号通路分别为钙信号通路、神经活性配体-受体相互作用和cAMP信号通路.GO分析得到主要的生物过程聚类分析包括氮化合物的细胞反应、血液循环和神经递质水平的调节;细胞组成聚类分析主要有突触后膜、突触后、突触膜;核心分子功能聚类分析包括神经递质受体活性、核糖核酸聚合酶Ⅱ特异性脱氧核糖核酸结合转录因子结合,以及乙酰胆碱结合.另外,秀丽隐杆线虫实验结果表明,黄芪葛根汤可以延缓线虫肌肉组织因过度表达Aβ1-42导致麻痹表型的AD样病理特征,其中0.5 g·L-1的抗AD活性最优.进一步实验证明黄芪葛根汤还可显著减缓泛神经元过度表达Aβ1-42导致的线虫对外源5-羟色胺超敏感的AD样病理特征.结论 黄芪葛根汤可能通过对钙离子稳态失衡、线粒体氧化应激、炎症等的调节治疗AD,且实验研究证明黄芪葛根汤对AD线虫有治疗作用.

目的 基于蛋白质组学以秀丽隐杆线虫为模式生物探究鸦胆子油的急毒性及抗肿瘤机制.方法 提取、制备鸦胆子油乳,稀释成不同浓度后加入96孔板,置于恒温摇床中分别培养1 d观察线虫的死亡比率;培养5 d后观察野生型线虫的比率,分析鸦胆子油乳的急毒性与抗肿瘤活性.提取线虫总蛋白,运用串联质谱标签定量蛋白质组学研究药物干预前后的差异蛋白情况.结果 鸦胆子油的毒性较小,浓度为25 mg·L-1时,线虫的死亡率为46％;与对照组相比,给药组均对Ras基因突变的线虫多阴门表型有不同程度的抑制作用,且随着浓度的增大,其对秀丽隐杆线虫的多阴门表型的抑制作用增强;蛋白质组学数据分析筛选出127个差异蛋白,其中上调蛋白97个,下调蛋白30个;GO功能富集显示,主要与DNA复制、DNA链延伸、染色质沉默的负调控、单链DNA解旋酶活性、氧化还原酶活性等功能有关.KEGG富集显示主要与TGF-β信号通路、Wnt信号通路、Hedgehog信号通路、MAPK信号通路等多条信号通路相关.结论 鸦胆子油毒性较小,且能够明显下调Ras/MAPK通路,具有较好的抗肿瘤活性.

Background To explore the mechanism of Maxing Shigan Decoction in the treatment of myocardial injury and lung injury through network pharmacology and molecular docking technology. Methods In Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) and the Comparative Toxicogenomics Database, National Center for Biotechnology Information database, Online Mendelian Inheritance in Man database, the compounds and targets of each drug in Maxing Shigan Decoction and the targets of “acute lung intervention” and “myocardial injury” diseases were searched. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed by the DAVID database. GOLD 5.1 was used for molecular docking. Results Maxing Shigan Decoction includes 327 compounds and 2722 targets, including 30 key targets. 2125 items were obtained by GO enrichment analysis, including 2047 items of Biological Process, 28 items of Cell Composition and 50 items of Molecular Function. The KEGG pathway was enriched to obtain 149 pathways. The results of molecular docking showed that Gancaonin H and Licorice Glycoside E were well combined with Angiotensin-Converting Enzyme 2-A (ACE2-A) and Angiotensin-Converting Enzyme 2-B (ACE2-B), respectively, and Licorice was well combined with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Interleukin 6 (IL-6). Supraene is an active compound of Ephedra . It has good binding with ACE2-A, ACE2-B, GM-CSF and IL-6, respectively. (6Z, 10E, 14E, 18E)-2, 6, 10, 15, 19, 23- hexamethyletracosa-2, 6, 10, 14, 18, 22- hexaene are the active compounds of Almond , which are well combined with ACE2-A, ACE2-B, GM-CSF and IL-6. Conclusion Maxing Shigan Decoction may act on ACE2, GM-CSF and IL-6 targets through the active compounds Supraene of Ephedra , and Almond (6Z, 10E, 14E, 18E)-2, 6, 10, 15, 19, 23-hexamethyletracosa-2, 6, 10, 14, 18, 22-hexaene. Gancainin H and licorice Glycide E are the active compounds of Licorice , act on A and B sites of ACE2 respectively, and Glycyrin acts on GM-CSF and IL-6 targets, coordinating multiple signal pathways to play anti-inflammatory and antiviral roles to prevent and treat lung and heart injury caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

2019年12月以来,武汉首先发现新型冠状病毒肺炎,其他城市随后出现此类病例。由新型冠状病毒导致的疾病由世界卫生组织正式命名为COVID-19（coronavirus disease 2019）。国家卫健委以及其他省市先后对COVID-19进行辨证分型,并提供对应的中医药治疗方案。中医认为该疫病属"湿毒之邪",治疗的最佳原则为早发现早治疗,中医和西医各有优势,可以优势互补,不能互相取代。因此全面收集中医药治疗COVID-19的中医药用药方案,进行系统分析,尤其是对中医药治疗COVID-19的药理学基础进行分析,为中药处方治疗COVID-19的合理性提供参考以及为各省市更新诊疗方案提供依据。

新型冠状病毒肺炎(COVID-19)严重危害着我国人民的生命健康.目前尚无针对COVID-19的特效药物,因此,预防对本病的防控意义重大.国家及各省市卫生管理部门针对此次疫情相继发布的《新型冠状病毒感染的肺炎中医药诊疗方案》,其中大部分包含预防用药处方,显示了传统中医药“治未病”的理论特色,亦显示了各省区的用药特色.为此,搜集了全国中医诊疗方案中66个预防方,挖掘各省区的中医药预防方案的规律,统一用药思维,为COVID-19的预防提供参考.

目的:通过网络药理学以及现代药理学基础分析探讨宣肺化浊方治疗新型冠状病毒肺炎(COVID-19)的作用靶点及信号通路,阐述其可能的作用机制.方法:从TCMSP和BATMAN-TCM数据库搜索宣肺化浊方各中药的化合物及靶点,使用GeneCards,NCBI以及CTD数据库检索COVID-19靶点;通过STRING数据库构建蛋白质相互作用网络.采用Cytoscape3.7.0软件构建中药-归经网络图以及中药-化合物-关键靶点-疾病网络,利用Omicshare平台对共有靶点进行京都基因与基因组百科全书(KEGG)分析及基因本体(GO)分析.除此之外,检索多脏器损伤、免疫损伤以及重症急性呼吸综合征(SARS)的疾病靶点,将宣肺化浊方与之做映射,计算交集靶点占宣肺化浊方靶点的比例.结果:宣肺化浊方共10味中药,其中有6味归肺经,5味归脾经,5味归胃经.化合物共409个,相对应的靶标2 271个.宣肺化浊方的靶点与新冠肺炎有8个相同的炎症因子,每个炎症因子对应多个化合物.宣肺化浊方与COVID-19有135个交集靶点,筛选得到36个关键靶点.KEGG通信号通路富集筛选得到172条信号通路(P＜0.05),GO分析得到生物过程结果有4 000个,细胞组成有254个,分子功能有408个(P＜0.05)).宣肺化浊方与各脏器损伤靶点和免疫损伤靶点的共有靶点较多,且共有靶点/XFHZP靶点的比例在7.6％～97.8％,宣肺化浊方与SARS有173个交集靶点.结论:宣肺化浊方可能通过发挥抗炎、保护脏器损伤、免疫等作用治疗新冠肺炎,这将为治疗新冠肺炎药物的开发提供一定的理论依据.