Matrine,oxymatrine, and compound Kushen injection from the roots of Sophora flavescens: an overview of their anticancer activities

In the present review, we updated current information on the chemistry, contents, and anticancer properties of matrine (MT), oxymatrine (OMT), and compound Kushen injection (CKI). The anticancer properties were focused on lung, breast, and liver cancer cells because they are most susceptible. Sources of information were from Google, Google Scholar, PubMed, PubMed Central, Science Direct, PubChem, J-Stage, Directory of Open Access Journals (DOAJ), and China National Knowledge Infrastructure (CNKI). Reference was also made on botanical websites, such as Flora of China and World Flora Online. MT and OMT are dominant quinolizidine alkaloids from the roots of Sophora flavescens (Kushen) of the family Fabaceae. Against lung, breast, and liver cancer cells, MT and OMT inhibit cell proliferation; induce cell cycle arrest, apoptosis, and autophagy; restrict angiogenesis; and inhibit cell metastasis, invasion, and migration. The processes involve various molecular targets and signaling pathways. CKI is a traditional Chinese medicine (TCM) composed of root extracts of S. flavescens and Smilax glabra (Baituling) of the family Smilacaceae. With MT and OMT as major components, CKI has been approved for the treatment of cancer in China more than 20 years ago. In recent years, systematic reviews and meta-analysis have been undertaken to evaluate the anticancer effects of CKI. When CKI is used alone and in combination with chemotherapy of western medicine, there is much to be learned concerning their interactions besides their individual and integrated efficacy. Some perspectives of MT, OMT, and CKI are discussed, and their suggestions for future research are provided.     

基于网络药理学和分子对接法探索复方一枝蒿颗粒治疗新型冠状病毒肺炎的潜在分子机制

目的 通过网络药理学及分子对接技术探寻复方一枝蒿颗粒治疗新型冠状病毒肺炎的作用机制。方法 应用TCMSP数据库、BATMAN-TCM数据库及文献收集复方一枝蒿颗粒活性成分及潜在靶点。通过TTD、GeneCards和OMMI数据库检索新型冠状病毒肺炎相关的靶点。将复方一枝蒿颗粒药物靶点和新型冠状病毒肺炎相关基因取交集，使用String数据库构建靶蛋白相互作用（PPI）网络。通过Cytoscape构建“药物–活性成分–靶点基因–疾病”网络。对交集靶点进行GO功能、KEGG通路富集分析。利用Autodock_vina软件对活性成分和靶点进行分子对接。结果 共筛选92个活性成分，1 627个靶点，新型冠状病毒肺炎疾病靶点464个，两者取交集筛选出87个潜在靶点。GO功能富集得到2 040个条目（P＜0.05），与病毒过程、参与共生相互作用的生物过程、活性氧代谢过程的调节、与宿主相互作用的生物过程、病毒生命周期、炎症反应的调节等生物学过程有关。KEGG通路分析共得到150条通路，与新冠肺炎密切相关的有人巨细胞病毒感染、结核、COVID-19、IL-17信号通路等。分子对接结果证实，筛选的靶点受体蛋白与活性成分可以较好地结合。结论 复方一枝蒿颗粒可通过多组分、多靶点和多途径的方式对新型冠状病毒肺炎产生治疗作用。     

Repurposing of parenterally administered active substances used to treat pain both systemically and locally

Pain is a constant in our lives. The efficacy of drug therapy administered by the parenteral route is often limited either by the physicochemical characteristics of the drug itself or its adsorption–distribution–metabolism–excretion (ADME) mechanisms. One promising alternative is the design of innovative drug delivery systems that can improve the pharmacokinetics |(PK) and/or reduce the toxicity of traditionally used drugs. In this review, we discuss several products that have been approved by the main regulatory agencies (i.e., nano- and microsystems, implants, and oil-based solutions), highlighting the newest technologies that govern both locally and systemically the delivery of drugs. Finally, we also discuss the risk assessment of the scale-up process required, given the impact that this approach could have on drug manufacturing.Teaser: The management of pain by way of the parenteral route can be improved using complex drug delivery systems (e.g., micro- and nanosystems) which require high-level assessment and shorten the regulatory pathway.     

多指标综合加权评分法优选复方夏枯草洗剂提取工艺研究

[目的] 优选复方夏枯草洗剂的提取工艺。[方法] 采用L₉（3⁴）正交设计，以迷迭香酸、丹酚酸B的含量及出膏率的综合评分为指标，考察料液比、提取时间、提取次数对提取效果的影响，优选复方夏枯草洗剂的最佳提取工艺。[结果] 根据综合评分的结果，优选出最佳提取工艺为加8倍水，提取3次，每次0.5 h。[结论] 该工艺准确可靠，可行性好。     

益气养阴解毒方联合环磷腺苷葡胺注射液治疗病毒性心肌炎35例

目的:探讨益气养阴解毒方联合环磷腺苷葡胺注射液对病毒性心肌炎患者心功能及外周血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)和干扰素-γ(interferon-γ,IFN-γ)水平的影响。方法:将70例病毒性心肌炎患者按照随机数字法分为对照组和观察组,每组各35例。两组患者均给予常规治疗,对照组在常规治疗的基础上给予环磷腺苷葡胺注射液静脉滴注,观察组在对照组的基础上联合益气养阴解毒方治疗。比较两组患者的临床疗效及治疗前后左室短轴缩短分数(left ventricular shortening fraction,LVFS)、左心室射血分数(left ventricular ejection fraction,LVEF)、心脏指数(cardiac index,CI)、TNF-α、TGF-β1和IFN-γ水平。结果:观察组有效率为88.57%,对照组有效率为68.57%,两组患者有效率比较,差异有统计学意义(P<0.05)。两组患者治疗后LVEF、LVFS高于本组治疗前,且观察组高于对照组,差异具有统计学意义(P<0.05)。两组患者治疗后TGF-β1、TNF-α水平低于治疗前比较,IFN-γ高于治疗前,且观察组TGF-β1、TNF-α低于对照组,IFN-γ高于对照组,差异均有统计学意义(P<0.05)。两组患者不良反应发生率比较,差异无统计学意义(P>0.05)。结论:益气养阴解毒方联合环磷腺苷葡胺注射液治疗病毒性心肌炎疗效更显著,可减轻机体的炎症反应,恢复患者心功能。     

参附注射液对猪创伤性心脏骤停复苏后肾损伤的保护作用研究

目的探讨参附注射液对猪创伤性心脏骤停复苏后肾损伤的保护作用。方法国产健康雄性白猪21头,采用随机数字表法分为假手术组(Sham组,n=5)、创伤性心脏骤停复苏(TCA组,n=9)和参附组(SFI组,n=7)。Sham组只经历气管插管及动静脉置管,不经历放血、复苏等过程。TCA组匀速释放总血容量的40%,然后经电刺激法室颤5 min,心肺复苏5 min后常规液体复苏治疗。SFI组在TCA组基础上于复苏后5 min进行参附注射液的干预。于放血前10 min、复苏后1、3、6、24 h检测血清TNF-α、IL-6、肌酐(Cr)、尿素氮(BUN)水平。复苏后24 h经右侧耳缘静脉注射10%氯化钾液20 mL处死猪,迅速获取肾组织标本,应用原位末端标记法(TNUEL法)检测细胞凋亡情况,免疫组织化学法检测半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)的蛋白表达水平。结果TCA组中有8头猪复苏成功,SFI组和Sham组中所有猪复苏成功。与Sham组比较,TCA组血清Cr水平在复苏后24 h、BUN水平在复苏后1、3、6、24 h均明显增高(均P<0.05),TNF-α、IL-6水平在复苏后3、6、24 h明显增高(均P<0.05),复苏后24 h后肾组织细胞凋亡指数及Caspase-3表达增加(均P<0.05)。与TCA组比较,SFI组BUN水平复苏后3、6 h明显降低(均P<0.05),TNF-α、IL-6水平在复苏后3、6、24 h明显降低(均P<0.05),肾组织细胞凋亡指数和Caspase-3蛋白表达有所降低,但差异无统计学意义(均P>0.05)。结论在猪TCA复苏模型中,早期应用参附注射液能够明显减轻复苏后肾损伤。其机制可能与抑制系统炎症反应、减轻细胞凋亡有关。     

基于网络药理学和分子对接技术探讨生脉注射液抗新型冠状病毒肺炎的作用机制

目的采用网络药理学与分子对接技术探讨生脉注射液的活性成分和治疗新型冠状病毒肺炎(COVID-19)的潜在作用机制。方法利用TCMSP及BATMAN-TCM数据库筛选生脉注射液的活性化合物,通过TCMSP及Targetnet在线数据库预测作用靶点,通过Cytoscape3.7.1构建活性成分-作用靶点网络图;在GeneCards及OMIM数据库中以"coronavirus pneumonia"为关键词搜索冠状病毒肺炎相关疾病靶点,与生脉注射液化合物靶点进行交集筛选出共同靶点作为研究靶点,将共同靶点导入STRING数据库获取数据后在Cytoscape 3.7.1软件中构建蛋白质-蛋白质相互作用网络图;利用R语言进行GO(gene ontology)功能、KEGG(Kyoto encyclopedia of genes and genomes)通路富集分析,预测其作用机制,并构建"成分-靶点-通路"网络图;通过DiscoveryStudio 2.5软件对关键靶点进行分子对接分析。结果生脉注射液筛选得到22个活性化合物,分别为邻苯二甲酸二辛酯、β-谷甾醇、当归酰基戈米辛O、戈米辛A、戈米辛R、五味子丙素、内南五味子酯乙、长南酸、南五味子内酯、香蒲木脂素B、新杜松烷酸A、新杜松烷酸B、新杜松烷酸C、新南五味子木脂宁、五味子内酯A、五味子内酯E、五味子酸、尿苷、薯蓣皂苷元、鸟嘌呤核苷、N-反式阿魏酰酪胺、豆甾醇。相应作用靶点224个,与COVID-19的共同靶点16个,分别为CASP3、CASP8、PTGS2、BCL2、BAX、PRKCA、PTGS1、PIK3CG、F10、NOS3、DPP4、NOS2、TLR9、ACE、ICAM1、PRKCE,关键靶点涉及CASP3、PTGS2、NOS2、NOS3、ICAM1。GO功能富集分析得到生物过程(BP)条目771个,细胞组成(CC)条目11个,分子功能(MF)条目79个。KEGG通路富集分析筛选得到67条(P0.05)信号通路,主要涉及糖尿病并发症AGE-RAGE信号通路、凋亡通路、P53信号通路、小细胞肺癌通路等。分子对接结果显示与关键靶点对接较好的成分有五味子内酯E、豆甾醇、N-反式阿魏酰酪胺。结论生脉注射液中的活性化合物五味子内酯E、豆甾醇、N-反式阿魏酰酪胺等能作用于CASP3、PTGS2、NOS2、NOS3等靶点调节多条信号通路发挥抗炎、免疫调节、抗休克、增加血氧饱和度等作用,从而可能发挥对COVID-19的治疗作用。