虎杖解毒颗粒抗病毒的药效物质探究

目的探讨虎杖解毒颗粒防治新型冠状病毒肺炎的药效物质及作用机制。方法以“虎杖”“抗病毒”“冠状病毒机制”等为关键词,检索国内外相关文献,总结虎杖解毒颗粒抗病毒的药效物质、抗冠状病毒的药效物质、抗新型冠状病毒的潜在药效物质,并运用Cytoscape3.7.2软件进行分析。结果虎杖解毒颗粒抗病毒的药效物质包括板蓝根多糖、大黄素、野鸢尾苷元等53个成分,抗冠状病毒的药效物质包括白藜芦醇、大黄素、芦荟大黄素等89个成分,抗新型冠状病毒的潜在药效物质包括白藜芦醇、青蒿素、大黄素等19个成分。抗新型冠状病毒的潜在作用机制包括促进Ⅰ型干扰素抗病毒、抑制NF-κB、胞外信号调节激酶(ERK)/促分裂原活化的蛋白激酶(MAPK)、磷脂酰肌醇3激酶(PI3K)/AKT信号通路等。结论虎杖解毒颗粒中的多种成分具有抗病毒作用,其抗病毒和抗冠状病毒的机制可能与促进Ⅰ型干扰素抗病毒,以及抑制NF-κB,ERK/MAPK,PI3K/AKT信号通路有关,但需通过相关试验进行验证。     

儿童新型冠状病毒肺炎药物治疗研究进展

新型冠状病毒(severe acute respiratory syndrome corona virus,SARS-CoV)-2感染在全球暴发,目前尚无明确有效的抗病毒药物治疗SARS-CoV-2感染。结合以往临床一线治疗新型冠状病毒肺炎(corona virus disease 2019,COVID-19)的经验,从核苷类似物、蛋白酶抑制剂等抗病毒药物、免疫相关药物及恢复期血浆治疗等方面,本文就儿童COVID-19药物治疗研究进展作一综述。     

2019新型冠状病毒感染潜在抗病毒治疗药物

2019新型冠状病毒(2019 novel coronavirus,2019-nCoV)感染是一种新发、突发传染性疾病,传染性强[1],2019-nCoV与严重急性呼吸综合征相关冠状病毒(SARS-CoV)和中东呼吸综合征相关冠状病毒(MERS-CoV)近缘,均可引起重症肺炎、呼吸衰竭和多器官功能障碍。由该病毒感染引起的疾病被称为2019冠状病毒肺炎(corona virus disease 2019,COVID-19),目前针对2019-nCoV尚无特异抗病毒药物。基因组研究表明,2019-nCoV与SARS-CoV、MERS-CoV分别有79%和50%的基因序列相似性[2],推测SARS-CoV、MERS-CoV中的抗病毒治疗经验及证据对于2019-nCoV有一定借鉴意义。为更好地协助一线临床医师开展救治工作,本文针对2019-nCoV的防控方案及既往SARS-CoV、MERS-CoV的诊疗方案、专家共识和指南,对目前6种可供选择的抗病毒药物(干扰素α、利巴韦林、洛匹那韦/利托那韦、瑞德西韦、阿比多尔及氯喹/羟氯喹)研究进行综述,其中瑞德西韦在我国正展开Ⅲ期临床试验,另外5种已在国内上市的药物针对2019-nCoV的抗病毒疗效尚未明确。     

新型冠状病毒性肺炎临床特征及抗病毒药物治疗方案进展

2019年12月,湖北省武汉市出现多例新型冠状病毒肺炎病例。2020年2月,世界卫生组织(WHO)将该病毒正式命名为严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2),SARS-CoV-2所导致的感染被命名为新型冠状病毒肺炎(corona virus disease 2019,COVID-19)。冠状病毒(coronavirus,CoV)属冠状病毒科,是一组具有外套膜的正链单股RNA病毒,可导致动物和人类不同程度的呼吸道、肠道、肝脏和神经系统疾病[1-3]。包括4属:α-CoV、β-CoV、γ-CoV、δ-CoV。短短20年来,冠状病毒已引发了包括严重急性呼吸综合征冠状病毒(severe acute respiratory syndrome coronavirus,SARS-CoV)感染、中东呼吸综合征冠状病毒(middle east respiratory syndrome coronavirus,MERS-CoV)感染和目前的SARS-CoV-2感染在内的3次传染病大流行[4-6]。三种冠状病毒均属于β-CoV,传播速度快,重症可导致严重呼吸综合征和死亡。目前,COVID-19已成为全球关注的突发公共卫生事件,但仍缺乏直接抗病毒治疗药物。     

瑞德西韦(remdesivir)抗冠状病毒应用前景

瑞德西韦是腺苷类似的氨基磷酸酯前体药,RNA依赖性的RNA聚合酶(RNA-dependent RNA-polymerases,RdRp)抑制剂,在细胞试验和动物试验中,它对RNA病毒(如MERS和SARS)具有广谱抗病毒活性,且毒性低。作为治疗2019新型冠状病毒(2019 novel coronavirus,2019-nCoV)感染的潜在药物,目前已在中国开展III期临床试验。本文就该药物抗病毒机制、体外抗病毒活性、动物实验、毒理实验、药动学和已进行的临床研究情况等进行全面综述,供临床参考。     

新型冠状病毒肺炎潜在治疗药物——洛匹那韦/利托那韦

新型冠状病毒即严重急性呼吸综合征冠状病毒2(severe acute respiratory syndrome coronavirus2,SARS-CoV-2)是2019年12月在中国首次发现的一种新型病毒,其在全国范围内快速传播,造成了严重的新型冠状病毒肺炎(corona virus disease 2019,COVID-19)疫情。目前尚没有针对性的药物或疫苗可用于临床防治。洛匹那韦/利托那韦复方制剂(lopinavir and ritonavir compound,LPV/r;商品名:克力芝)是由艾伯维公司研发的一种临床已用于治疗人类免疫缺陷病毒1型感染的蛋白酶抑制剂,有临床研究证明其可显著降低SARS冠状病毒感染患者的死亡率。研究表明LPV/r可通过结合冠状病毒的3C样蛋白酶发挥抗冠状病毒作用。《新型冠状病毒肺炎诊疗方案》(试行第六版)已推荐将其作为COVID-19治疗的试用药物,目前有13项基于LPV/r的干预治疗临床试验正在开展。本文就LPV/r的基本信息、作用机制和临床试验等情况作一概述。     

某院治愈的首例新型冠状病毒(2019-n CoV)肺炎病例分析

新型冠状病毒肺炎( COVID-19 )是一种全新的、突发的、传染性强,传播力广的疫病.2019新型冠状病毒( Novel coro-navirus pneumonia ,2019-nCoV )与严重急性呼吸综合征病毒(SARS-CoV)和中东呼吸综合征病毒(MERS-CoV)高度同源,但又截然不同〔1〕.与SARS-...     

氯喹抗冠状病毒的作用及其安全性研究进展

冠状病毒作为一种人畜共患病毒,可引起肺部感染,严重的会引起死亡甚至肆虐传播。2019年12月底陆续出现了新型冠状病毒——严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染引起的新型冠状病毒肺炎(COVID-19)患者。针对冠状病毒,目前并无特效药。氯喹作为一种经典抗疟药,可通过改变内吞体pH值、自噬反应以及改变病毒包膜的糖基化模式等途径发挥抗病毒效应。在细胞水平上,氯喹对SARS-CoV、中东呼吸综合征冠状病毒(MERS-CoV)和SARS-CoV-2均有抑制作用。近期临床研究初步表明,氯喹可以提高COVID-19患者成功救治率,改善预后。由于氯喹副作用较多,近些年已经较少用于临床,氯喹用于治疗COVID-19的安全性需要深入评估。本文结合氯喹的药理学特点,针对氯喹抗冠状病毒感染的作用及其安全性作一概述,以期为其临床合理应用提供参考。     

抗病毒颗粒的临床研究现状

抗病毒颗粒是根据经典名方研制而成的,用于治疗上呼吸道感染及流行性感冒的独家中药复方制剂。本文综述了抗病毒颗粒在新发传染性疾病和新型冠状病毒肺炎(COVID-19)等疾病领域的临床应用潜在价值。     

妊娠合并新型冠状病毒肺炎的临床特点及管理策略

新型冠状病毒肺炎是一种新型的、具有高度传染性的病毒性肺炎,它已被确定为人畜共患病,导致此次疾病的病原体类似于严重急性呼吸综合征冠状病毒（SARS-CoV）和中东呼吸综合征冠状病毒,在人群之间具有强大的传染性,被命名新型冠状病毒（2019-nCoV）,对全球公共卫生构成了巨大威胁。随着2019-nCoV疫情的展开,孕期感染新型冠状病毒的临床特点、妊娠结局以及垂直传播的潜在风险已成为产科医生需重点考虑的问题。病毒核酸检测联合影像学检查是新冠肺炎快速标准的诊断方法,对防止随后的继发性传播至关重要。对2019-nCoV疾病特点及流行病学的掌握有助于制定有效的预防和管理策略。对高危孕产妇进行专案管理,普及防疫相关知识,对确诊患者进行多学科诊治,规范的个体化治疗有利于良好的母婴结局。     

黄丹结肠透析液的质量标准

目的建立黄丹结肠透析液的质量标准.方法用薄层色谱法时大黄、川芎、丹参进行定性鉴剐,用高效液相色谱法测定制剂中大黄素的含量.结果薄层色谱鉴定方法专属性强.大黄素平均回收率为98.6%,RSD为0.98%.结论本法简便、准确、灵敏、重现性好,可用于该制剂的质量控制.     

大黄素衍生物的合成及其应用研究进展

大黄素拥有利尿、引起血管舒张、抗菌、抗病毒、抗肿瘤等多种生物活性。但由于大黄素本身水溶性差、毒副作用大等缺点．近年来对大黄素的结构修饰得到了广泛的关注。本文综述了近年来国内外大黄素衍生物的最新合成进展,重点介绍一些具有较高生物活性的大黄素衍生物的合成报道。     

安太胶囊质量标准的提升研究

目的： 完善和提高安太胶囊的质量标准。方法： 采用薄层色谱法（TLC）对安太胶囊中大豆异黄酮、大黄、肉桂进行定性鉴别；采用高效液相色谱法（HPLC）对安太胶囊中大黄素进行含量测定，色谱柱为Kromasil C₁₈（250 mm×4.6 mm，5 μm），流动相为甲醇-0.1%磷酸溶液（97：3），检测波长为290 nm，流速为1.0 mL·min^-1，柱温为室温，进样量为20 μL。结果： 在TLC图谱中，斑点清晰，分离度好，阴性样品无干扰。大黄素在4.4~22 μg·mL^-1范围内与峰面积呈良好线性关系（r=0.999 9），平均加样回收率为97.87%（RSD=1.8%，n=6），精密度、稳定性和重复性试验的RSD分别为0.32%、0.26%和0.19%（n=6），大黄素的平均含量为0.115 mg/粒（n=3）。结论： 该方法快速、准确、专属性强，可作为安太胶囊质量控制的方法，并初步拟定其有效成分大黄以大黄素（C₁₅H₁₀O₅）计，每粒含大黄素不低于0.05 mg。     

Emodin is a novel alkaline nuclease inhibitor that suppresses herpes simplex virus type 1 yields in cell cultures

Background and purpose:Most antiviral therapies directed against herpes simplex virus (HSV) infections are limited to a small group of nucleoside analogues that target the viral polymerase. Extensive clinical use of these drugs has led to the emergence of resistant viral strains, mainly in immunocompromised patients. This highlights the need for the development of new anti-herpesviral drugs with novel targets. Herein the effects of a plant anthraquinone, emodin, on the HSV-1 alkaline nuclease activity and virus yields were investigated.Experimental approach:HSV-1 alkaline nuclease activity was examined by nuclease activity assay. Inhibition of virus yields was measured by plaque reduction assay and immunohistochemical staining. Interaction between emodin and alkaline nuclease was analysed by docking technology.Key results:Emodin specifically inhibited the nuclease activity of HSV-1 UL12 alkaline nuclease in a biochemical assay. Plaque reduction assay revealed that emodin reduced the plaque formation with an EC(50) of 21.5+/-4.4 muM. Immunohistochemical staining using the anti-nucleocapsid protein antibody demonstrated that emodin induced the accumulation of viral nucleocapsids in the nucleus in a dose-dependent manner. Docking analysis further suggested that the inhibitory effect of emodin on the UL12 activity may result from the interaction between emodin and critical catalytic amino acid residues of UL12.Conclusions and implications:Our findings suggest that emodin is a potent anti-HSV agent that inhibits the yields of HSV-1 via the suppression of a novel target, UL12.British Journal of Pharmacology (2008) 155, 227-235; doi:10.1038/bjp.2008.242; published online 16 June 2008.     

Differences in pharmacokinetics and ex vivo antioxidant activity following intravenous and oral administrations of emodin to rats

Emodin, a natural anthraquinone polyphenol, has been reported to possess promising in vitro antioxidation, anticancer and anti-inflammatory activities. Whether the in vitro bioactivities can predict in vivo effects remained an unanswered question without understanding emodin pharmacokinetics in animals. To fill this blank, this study investigated the biological fate of emodin in rats. Emodin was intravenously (5.0 mg/kg) and orally (20.0 and 40.0 mg/kg) administered to rats. Blood samples were assayed by HPLC before and after hydrolysis with sulfatase and β-glucuronidase. It is observed that after intravenous bolus of emodin, the parent form of emodin declined rapidly, and emodin glucuronides, ω-hydroxyemodin (ω-OHE) and ω-OHE sulfates/glucuronides all emerged instantaneously. In contrast, when emodin was given orally, emodin glucuronides were exclusively present in serum, whereas emodin, ω-OHE and ω-OHE sulfates/glucuronides were not detected. In order to evaluate the in vivo antioxidation activity, the serum metabolites of emodin following intravenous and oral administrations were prepared from rats and characterized, followed by investigating the effects on 2,2′-azobis(2-amidinopropane hydrochloride)-induced hemolysis. The results suggested that the serum metabolites of oral emodin exhibited more promising free radical scavenging activity than those of intravenous emodin and emodin parent form. We suggest biologists to redirect their targets to emodin glucuronide. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2185–2195, 2010     

复方止痛湿敷剂的制备及疗效观察

目的 对复方止痛湿敷剂的制备与质量控制进行研究并进行临床疗效观察。方法 对主要成份大黄素、大黄酸、三七总皂苷等进行定性鉴别；进行动物皮肤刺激皮肤过敏试验；设立对照组进行临床疗效观察。结果 本制剂质量稳定，主要有效成份的鉴别特征性强，对皮肤刺激性小，临床疗效佳。结论 此制剂对急慢性扭伤、关节炎等引起的疼痛疗效良好。     

Emodin induces embryonic toxicity in mouse blastocysts through apoptosis

Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a major constituent of rhubarb, has a wide range of therapeutic applications. Previous studies have established that emodin inhibits cell proliferation and induces caspase 3-dependent apoptosis. However, its side-effects, particularly those on embryonic development, have not been well characterized as yet. In the current study, we examined the cytotoxic effects of emodin on mouse embryos at the blastocyst stage, subsequent embryonic attachment and outgrowth in vitro, and in vivo implantation by embryo transfer. Blastocysts treated with 25-75 μM emodin exhibited significantly increased apoptosis and a corresponding decrease in total cell number. Notably, the implantation success rate of blastocysts pretreated with emodin was lower than that of their control counterparts. Moreover, in vitro treatment with 25-75 μM emodin was associated with increased resorption of post-implantation embryos and decreased fetal weight. With the aid of an in vivo mouse model, we showed that consumption of drinking water containing emodin led to apoptosis and decreased cell proliferation, and inhibited early embryonic development to the blastocyst stage. Our findings support a degree of selective inhibition of retinoic acid receptors in blastocysts treated with emodin. In addition, emodin appears to induce injury in mouse blastocysts through intrinsic apoptotic signaling processes to impair sequent embryonic development. These results collectively indicate that emodin has the potential to induce embryonic cytotoxicity.     

The effects of emodin on the expression of cytokines and functions of leukocytes from Sprague-Dawley rats

Emodin has been reported to induce apoptosis in many human cancer cell lines, although its effects on leukocyte functions in vitro have not been demonstrated Therefore, the purpose of this study was to assess the effect of emodin on the phagocytosis of macrophages, the activity of natural killer cells and the expression of cytokines in leukocytes from Sprague-Dawley rats. Leukocytes, isolated from rats, were placed into culture plates for incubation with or without various concentrations of emodin for 1-6 hours and the functions of macrophages and natural killer cells were evaluated by flow cytometric analysis. The results indicated that emodin caused a decrease in phagocytosis of macrophages after treatment for up to 4 hours but 6-hour treatments led to an increase in the phagocytosis of macrophages. Further, emodin increased the activity of natural killer cells, both effects being dose-dependent. The levels of cytokines from the examined leukocytes were evaluated by ELISA and the results indicated that emodin increased the levels of IL-1beta and TNF-alpha, results which were confirmed by PCR assay for the mRNA expressions of the examined cytokines.