Recent advances in the antiviral activity of Forsythiae Fructus

Forsythiae Fructus,a well-known traditional Chinese medicine preparation derived from the dried fruits of Forsythia suspensa(Thunb.)Vahl,has been historically utilized for its heat-clearing and detoxification properties.Forsythiae Fructus has been reported to exhibit antiviral activity such as against SARS-CoV-2 and influenza virus.This review highlights the recent updates on the effects and underlying action mechanisms of compounds in and active fractions from Forsythiae Fructus and Chinese formulae containing Forsythiae Fructus.

Microwave assisted-semi bionic extraction of lignan compounds from Fructus Forsythiae by orthogonal design

Microwave assisted-semi bionic extraction (MASBE) process for lignans from Fructus Forsythiae was studied. The influences of solvent pH value, microwave power, dosage of solvent and irradiation time were investigated. Optimum extracting parameters were determined by orthogonal experiments as follows: pH value of solvent at first extraction is 5.5-6.0, that at the second extraction is 7-8; microwave power is 700 W; mass ratio of Fructus Forsythiae to water is 1-12; irradiation time is 10 min, and extracting times is two. Under these optimal conditions, the yield of lignans reaches 0.364%. Compared with the conventional extraction methods, the MASBE process has the advantages of high extraction rate, high extraction selectivity.

Forsythiae Fructus inhibits melanoma growth through activating MAPKs/Nrf2/HO-1 signaling and modulating glycerophospholipid metabolism

OBJECTIVE Forsythiae Fructus(Lianqiao)is a typical heat-clearing and detoxicating traditional Chinese medicine(TCM)herb,which has been traditionally used for treating cancer according to TCM theory.However,the underlying mechanism has not been fully explained.METHODS In this study,we investigated the antitumor effect of Forsythiae Fructus aqueous extract(FAE)on B16-F10 melanoma.RESULTS FAE strongly inhibited the tumor growth and metastasis formation in B16-F10 melanoma transplanted mice.The survival time of tumor-bearing mice was also significantly prolonged by FAE.The levels of ROS,MDA,TNF-αand IL-6 decreased,while GSH increased in the FAE treatment group,indicating FAE possesses strong anti-oxidative and anti-inflammatory activity.Western blotting analysis demonstrated that antioxidant proteins Nrf2 and HO-1,tumor suppressors P53 and p-PTEN,and the MAPK pathways in tumor tissues were upregulated by FAE treatment.Serum metabolomics analysis further uncovered that 17 metabolites mostly involving in glycerophospholipid metabolism were correlated with the antitumor effect of FAE.Notably,several lysophosphatidylcholines(LysoPCs)significantly decreased in tumor model group,while FAE treatment restored the changes of these phospholipids to about normal condition.LysoPC acyltransferase 1(LPCAT1)and autotaxin(ATX)highly expressed in melanoma and markedly downregulated by FAE were believed to be responsible for this modulation.CONCLUSION FAE exhibites strong antitumor activity against B16-F10 melanoma through activating MAPKs/Nrf2/HO-1 mediated anti-oxidation and anti-inflammation and modulating glycerophospholipid metabolism via downregulating LPCAT1 and ATX.Besides,it is suggested that serum LysoPCs could be potential biomarkers for the diagnosis and prognosis of melanoma.

Study on the mechanism of Fructus Forsythiae and Folium Nelumbinis on acute pharyngitis based on network pharmacology

Objective:To explore the mechanism of Lianqiao-Heye(Fructus Forsythiae and Folium Nelumbinis,FF-FN)drug pair in treating acute pharyngitis(AP)by network pharmacology.Methods:The chemical components and potential therapeutic targets of FF-FN drug pair were obtained from TCMSP firstly,and databases GeneCards,DrugBank,OMIM and PharmGKB were utilized to get the genes related to AP and the intersection of the results was obtained.Then Cytoscape software was used to construct drug-component-target network diagram to screen out the key compounds.Protein interaction network(PPI)was established using String database,and the core targets were screened by CytoNCA topology analysis.R language software was used for GO biological function analysis and KEGG pathway analysis.Finally,the docking verification of key compounds and core target molecules was carried out by AutoDock software.Results:A total of 38 active compounds and 917 potential therapeutic targets were obtained from FF-FN drug pair,while a total of 1534 targets were screened out for AP,among which,the number of intersection targets was 117.7 core targets were screened out from PPI core network,with JUN,TP53,CXCL8 and RELA included.A total of 2487 biological processes were involved in GO enrichment analysis,and 157 related pathways were screened out by KEGG.Based on results of molecular docking verification,the key compounds such as quercetin,luteolin and wogonin in FF-FN drug pair were proved capable of binding to the core targets and a good affinity was shown.Conclusion:FF-FN pair can intervene AP through multiple targets and multiple pathways,including PI3KAkts signaling pathway,AGE-RAGE signaling pathway and IL-17 signaling pathway.The combination of quercetin,luteolin,wogonin,kaempferol andβ-sitosterol with JUN,RELA,MAPK1,TNF and MYC can possibly be one of the mechanisms regarding to the therapeutic effect.

连翘与陈皮混合挥发油提取与包合工艺优化

目的优选保和颗粒组方中连翘、陈皮混合挥发油提取工艺及β-环糊精(β-CD)包合工艺。方法以饮片粉碎粒度、提取时间、加水倍数为考察因素,挥发油收率为评价指标,采用L_(9)(3^(4))正交试验法优选。以β-CD与挥发油比例(g∶m L)、包合时间、包合温度为考察因素,挥发油包合率、包合物收率、包合物含油量的综合评分为评价指标,同上法优选包合工艺并验证。结果最佳提取工艺,将饮片粉碎至20目,加10倍水提取3 h。最佳包合工艺,β-CD∶挥发油为7∶1(g∶m L),45℃下包合反应3 h;紫外光谱扫描、X射线衍射、扫描电镜、薄层色谱等结果均证明形成了稳定的包合物。制成的包合物中连翘及陈皮混合挥发油的包合率为95.13%,包合物收率为87.84%,包合物含油量为10.29%,综合评分为76.70分。结论优化后的连翘及陈皮混合挥发油提取、包合工艺稳定可行。

银翘的本草考证

银翘是金银花和连翘的合称。两者都是清热解毒药物,相须为用起到协同作用,提高疗效。作者通过对历代古籍及权威药学专著的收集、整理、比较、分析,分别对连翘和金银花的名称、性味归经、功效主治以及用药部位进行考证,结果发现历代本草著作对连翘、金银花记载不尽相同。连翘早期名为异翘,性味由“苦、平”转为“味苦性寒或微寒”,用药部位由根部发展为全叶,具有消肿排脓、清热解毒、疏散风热的功效。忍冬为金银花早期用名,只采用茎叶作为用药部位到茎、叶、花均可入药,属“寒”性药物,具有清热解毒之功效。考证结果可为今后成方制剂开发及临床应用提供重要参考。

不同产地连翘质量的研究现状分析

目的总结不同产地连翘质量控制的研究现状。方法通过收集连翘中主要化学成分的研究文献资料,对不同产地连翘中主要化学成分(总挥发油、连翘酯苷A、连翘酯苷B、连翘苷和微量元素钠、锰、锌、铁、镁、钾、钙、铬、锗、硒及重金属铅、镉、砷、汞、铜)的含量研究结果进行数据收集和比较。结果由统计分析结果可知,陕西、湖北、安徽的样本挥发油质量分数均值约为1.7%,为最高;河南、陕西和山西的连翘酯苷A含量排名靠前,分别为5.47%、4.90%、4.83%;山西连翘中的连翘酯苷B样本量最高且含量均值高于其他产地;山西连翘微量元素优势较大,山西运城、太原、临汾、晋中产地的连翘中的Mn、Fe、Mg、K、Ca、Cr、Ge、Se质量分数居于前列,Na、Zn分别是河南三门峡、河北邯郸产地较优;各产地连翘的重金属含量均未超标。结论山西、河南、陕西、河北作为连翘的主要产区,多种化学成分的质量分数普遍高于其他产区,品质更为优良。本文为开展不同产地连翘的共性和个性特征研究提供了数据支撑,为各产地连翘的质量控制提供了参考。

连翘化学成分、药理作用及安全性评价的研究进展

连翘为临床常用的清热解毒类中药,主要含有苯乙醇苷类、木脂素类、萜类及挥发油、黄酮类等化学成分。大量研究证实连翘具有抗炎、抗菌、抗病毒、抗癌等多种药理作用,且安全性较高。该文系统综述了连翘的化学成分、药理作用及安全性的研究进展,以总结连翘的相关研究成果,并为其进一步的开发研究和临床应用提供思路。

连翘抗猪繁殖与呼吸综合征病毒的机制分析

【目的】用网络药理学方法探明连翘抗猪繁殖与呼吸综合征病毒(PRRSV)的潜在有效成分和作用机制。【方法】在TCMSP数据库收集连翘的潜在活性成分与作用靶点,在CTD数据库和GeneCards数据库收集PRRSV疾病靶点,获取两者的交集靶点后构建蛋白-蛋白互作网络,并进行基因本体(GO)功能富集分析和KEGG通路分析,之后对筛选出的主要活性成分和核心靶点进行分子对接验证。【结果】连翘有24种潜在活性成分和243个潜在作用靶点,PRRSV疾病有3368个作用靶点,两者有122个交集靶点。GO功能富集得到890个条目,主要涉及基因表达的正向调控、对外源性刺激的反应、细胞外空间、胞外区等、酶的结合及相同蛋白的结合等。KEGG通路分析共获得176个条目,主要涉及磷脂酰肌醇-3-激酶-蛋白激酶B(PI3K-Akt)、丝裂原活化蛋白激酶(MAPK)、白介素-17(IL-17)和肿瘤坏死因子(TNF)等信号通路。进一步分析显示,连翘抗PRRSV的主要潜在活性成分有槲皮素、山奈酚、木犀草素及连翘酯苷A等,核心靶点有TNF、白细胞介素6、白细胞介素1β、肿瘤蛋白p53、基质金属蛋白酶9、半胱氨酸天冬氨酸蛋白酶3、前列腺素内过氧化物合成酶2和表皮生长因子受体。分子对接结果显示连翘的潜在主要活性成分与核心靶点之间均能实现良好结合。【结论】连翘抗PRRSV主要活性成分可能为槲皮素、山奈酚、木犀草素及连翘酯苷A,可能主要通过PI3K-Akt、MAPK、IL-17和TNF等信号通路发挥作用。

高效液相色谱法测定家种连翘中山柰酚含量

目的建立测定家种连翘中山柰酚含量的高效液相色谱(HPLC)法。方法色谱柱为Shim-pack VP-ODS柱(250 mm×4.6 mm,4.6μm),流动相为甲醇-0.4%磷酸水溶液(50∶50,V/V),流速为1.0 mL/min,检测波长为365 nm,柱温为30℃,进样量为10μL。结果山柰酚质量浓度在0.01~0.5 mg/mL范围内与峰面积线性关系良好;精密度、稳定性、重复性试验结果的RSD均小于5%;平均加样回收率为97.30%,RSD为2.13%(n=6);湖北省十堰市郧西县8个村家种连翘中山柰酚含量为0.0377~1.0887 mg/g。结论该方法灵敏、可重复,测定结果准确,可用于家种连翘中山柰酚含量的测定。

基于R语言的专利中药复方防治呼吸道传染病的用药规律研究

【目的】挖掘专利中药复方防治呼吸道传染病的遣方用药规律,为呼吸道传染病的防治提供参考。【方法】在国家专利数据库中收集防治呼吸道传染病的中药复方,经数据筛选与规范化后,利用R语言进行数据挖掘。【结果】共纳入429首中药专利复方,涉及中药846味;高频中药有26味,使用频次居前10位的药物分别为甘草、金银花、黄芩、连翘、桔梗、百部、苦杏仁、黄芪、柴胡、薄荷。高频中药主要为清热解毒药和补气药;所涉中药药性以寒为主,药味多为苦、甘、辛,主归肺经;关联规则分析得到19条核心关联规则、多个药物组合;聚类分析得到3个药物聚类。【结论】专利中药复方防治呼吸道传染病时注重寒温相配、宣降相伍,着重宣散肺邪、清热解毒,同时不忘益气和中、滋阴润燥,使祛邪不伤正、扶正不敛邪。

Metabolomics Analysis of Metabolites in Forsythia suspense Fruit Using UPLC/ESI-Q TRAP-MS/MS

Forsythiae Fructus,the fruit of Forsythia suspense is a traditional Chinese hebal medicine that has the antiviral and antioxidant effects in China.Modern analytical chemistry studies showed that the extracts of Forsythiae Fructus contain many bioactive components,such as flavonoids,lignans,phenolic acids,and terpenoids,which can be used to anti-inflammatory and treat toxicity,tonsillitis,ulcers,pharyngitis and acute nephritis.In order to study the types and quantities of metabolites in Forsythiae Fructus,we isolated,identified and analysed metabolites between two varieties of Forsythiae Fructus using UPLC/ESI-Q TRAP-MS/MS.The results showed that a total of 407 metabolites were identified in Forsythiae Fructus using UPLC/ESI-Q TRAP-MS/MS,including 21 terpenoids,68 phenolic acids,63 flavonoids,43 amino acids and derivatives,22 alkaloids,55 lipids,24 lignans and coumarins,31 nucleotides and derivatives,29 organic acids,and 51 other metabolites.Among,lignans and coumarins,terpenoids,organic acids,lipids,and phenolic acids were rich in Forsythiae Fructus,which accounted for more than 60%of the total metabolite content.Differential metabolite analysis revealed that 80 metabolites differed significantly between the two types of Forsythiae Fructus.Our results greatly enrich the Forsythiae Fructus phytochemical composition database and provide valuable information for further study of the metabolites of Forsythiae Fructus.

中国不同地区连翘精油成分比较分析

为了探讨连翘生长环境和采收时间的影响,对我国主产区连翘精油进行了系统评价。采用GC-MS技术对不同产地的青翘(green Forsythiae Fructus,GF)和老翘(ripe Forsythiae Fructus,RF)中的精油成分进行了分析,为连翘的资源化利用提供参考。共鉴定出54种化合物,其中常见化合物12种,烯烃和醇类是最丰富的两种成分,且结构多样。基于主成分分析(PCA)的质量评价表明,湖北武汉RF、陕西洛南RF和安徽六安RF的综合评价得分较高;PCA和聚类分析(CA)能够区分样品中的GF和RF,也表明,采收期和区域环境共同影响连翘精油的成分。从精油成分角度考虑,应优先选用老翘进行开发和利用。应用精油的特性作为连翘采收期和区域环境的化学分类标志是可行的。

麻黄连翘赤小豆汤加减治疗湿热咳嗽临床研究

目的:观察麻黄连翘赤小豆汤加减治疗湿热咳嗽的临床疗效及其对患者临床症状评分及炎症反应的影响。方法:将136例湿热咳嗽患者按照随机数字表法分为对照组和观察组,每组各68例。对照组给予常规治疗,观察组在对照组治疗的基础上加用麻黄连翘赤小豆汤加减。比较两组患者的临床疗效及治疗前后临床症状评分、生活质量综合评定问卷-74(generic quality of life inventory-74,GQOLI-74)评分变化情况,采用酶联免疫法检测两组患者治疗前后肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、超敏C反应蛋白(hs-C reactive protein, hs-CRP)及白细胞介素-8(interleukin-8,IL-8)。结果:观察组有效率为95.59%,对照组有效率为83.82%,两组患者有效率比较,差异具有统计学意义(P<0.05)。两组患者治疗后咳嗽、咳痰、饮食、大便、小便、睡眠等临床症状评分低于本组治疗前,且观察组低于对照组(P<0.05)。两组患者治疗后TNF-α、IL-6、IL-8、hs-CRP水平低于本组治疗前,且治疗后观察组低于对照组(P<0.05)。两组患者治疗后GQOLI-74评分高于本组治疗前,且治疗后观察组高于对照组(P<0.05)。结论:麻黄连翘赤小豆汤加减治疗湿热咳嗽,可缓解患者的临床症状,减轻炎症反应,提高生活质量。

不同产地、不同炮制方式连翘的主要化学成分含量及抗菌活性比较评价

目的对不同产地、不同炮制方式连翘的主要化学成分含量及抗菌活性进行比较评价。方法选取不同产地、不同炮制方式的连翘,通过超高效液相色谱法(ultra performance liquid chromatography,UPLC)测定连翘苷、(+)松脂素-β-D-吡喃葡萄糖苷、芦丁、连翘酯苷A的含量;通过测定连翘煎煮液对金黄色葡萄球菌的最小抑菌浓度(minimum inhibitory concentration,MIC),比较抗菌活性。结果相同产地清蒸连翘的(+)-松脂素-β-D-吡喃葡萄糖苷、芦丁、连翘酯苷A及连翘苷的含量均显著高于生晒连翘;在清蒸连翘中,陕西产地连翘的4种主要化学成分含量均最高;在生晒连翘中,陕西产地连翘的松脂素-β-D-吡喃葡萄糖苷和芦丁含量最高,而山东产地的连翘酯苷A和连翘苷含量最高。不同产地、不同炮制方式连翘煎煮液的MIC值明显不同,清蒸连翘的MIC值显著低于生晒连翘。结论利用UPLC测定连翘主要化学成分含量的方法简便、准确,可用于不同产地、不同炮制方式连翘药材的区分及质量评价;连翘煎煮液对金黄色葡萄球菌的抑制作用的测定,也为其进一步抗菌作用机制研究提供参考。

不同采收期连翘HPLC指纹图谱建立及质量标志物预测分析、网络药理学研究

目的建立不同采收期连翘HPLC指纹图谱,并进行质量标志物预测分析、网络药理学研究。方法该药材50%甲醇提取液的分析采用ODS-2 HYPERSIL C_(18)色谱柱(250 mm×4.6 mm,5μm);流动相甲醇-0.2%冰醋酸,梯度洗脱;体积流量1.0 mL/min;柱温30℃;检测波长235 nm。采用主成分分析、正交偏最小二乘分析筛选青翘、老翘差异性成分,通过Swiss Target Prediction、Metascape等数据库分析差异性成分对应靶点和通路,在Cytoscape3.7.2软件中绘制“成分-靶点-通路”图,预测潜在质量标志物。结果36批样品HPLC指纹图谱中有14个共有峰,相似度大于0.97,筛选出9个差异性色谱峰(峰8、9、1、10、3、7、2、12、6)。5种差异性成分(松脂醇-β-D-葡萄糖苷、连翘酯苷A、芦丁、连翘苷、连翘酯苷I)通过TNF、HIF1A、PTGS2等49个靶点及AA、IL-17、mTOR等52条信号通路治疗相关疾病,可作为区分青翘、老翘的质量标志物。结论该方法稳定可行,可为连翘质量控制提供参考。

连翘的免疫调节活性成分及作用机制研究进展

连翘为临床常用中药,其活性成分包括苯乙醇苷类、木脂素类、酚酸类、黄酮类、萜类等,药理学研究表明连翘具有抑菌、抗炎、免疫调节等作用。总结连翘及其主要活性成分的免疫调节作用,揭示连翘及其主要活性成分通过作用于免疫器官脾脏和胸腺,T、B淋巴细胞、NK细胞、巨噬细胞等,缓解机体炎性反应,维持免疫系统的稳定性。其作用机制可能是通过降低肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)、白细胞介素(interleukin,IL)-1、IL-4、IL-6、IL-10和IL-18等炎症因子水平以及下调核转录因子-κB(nuclear factor kappa-B,NF-κB)等的表达,抑制促炎因子,并提高抗炎因子表达,发挥免疫调节作用。体外实验表明,连翘及其提取物可直接作用于大肠埃希菌等常见的革兰氏阴性菌,具有抑菌作用。此外,连翘对于由Th1/Th2细胞因子失衡所引起的类风湿性关节炎、系统红斑狼疮等自身免疫系统疾病也具有良好的免疫调节作用。系统地总结了连翘具有免疫调节作用的主要成分以及其免疫调节的作用机制,以期为连翘的临床应用和进一步的基础研究提供依据。

伤寒黄疸方“麻黄连轺赤小豆汤”证候分析、方中连轺考证及对连翘药用价值和研究的启示

麻黄连轺赤小豆汤是伤寒黄疸三方之一,但未受重视,方中连轺来源不明,地位作用难辨。本文首先对方中麻黄功用和全方证候进行剖析,确定了本方主要用来“清利湿热”以退黄;在此基础上考证“连轺”为“连翘之根”,而非“翘根”,今人以连翘代连轺使用效果相当;接着分析了方中“连翘”的重要地位,并根据连翘作用广泛但缺乏主治病证的特点对连翘药用、研究开发指出了一些有价值的方向,为深入开展连翘理论和实践研究提供了借鉴启示。

不同配伍比例金银花-连翘药对合煎颗粒与单煎颗粒混合的化学成分比较

目的:比较不同配伍比例金银花-连翘药对合煎颗粒与单煎颗粒混合后的化学成分差异。方法:采集不同配伍比例金银花-连翘药对(1∶2、1∶1、3∶2、2∶1、3∶1)合煎颗粒及单煎颗粒混合后样品的高效液相色谱指纹图谱,并采用SPSS 26.0对指纹图谱各共有峰的峰面积/称样量值进行独立样本t检验分析。结果:指纹图谱中确定了15个共有峰,并对其中9个特征峰进行了指认。独立样本t检验结果显示,当金银花、连翘配伍比例为1∶2、1∶1时,合煎颗粒与单煎颗粒混合样品中各色谱峰峰面积/称样量值的差异无统计学意义;当金银花、连翘配伍比例为3∶2时,合煎颗粒与单煎颗粒混合样品中峰3、8、10、12的峰面积/称样量值差异有统计学意义(P<0.05);当金银花、连翘配伍比例为2∶1时,合煎颗粒与单煎颗粒混合样品中除峰8外,其余14个特征峰的峰面积/称样量值差异无统计学意义;当金银花、连翘配伍比例为3∶1时,合煎颗粒与单煎颗粒混合样品指纹图谱的差异最大,除峰4、6、8外,其余12个特征峰的峰面积/称样量值差异有统计学意义(P<0.05)。结论:不同配伍比例金银花-连翘药对合煎颗粒与单煎颗粒混合的化学成分存在差异。

Box-Behnken响应面法优化连翘挥发油的胶体磨包合工艺

目的:优化连翘挥发油胶体磨包合工艺。方法:以连翘挥发油的包合率和包合物收率及综合评分为指标比较饱和水溶液法、超声法、胶体磨研磨法对连翘挥发油的包合效果。在单因素试验的基础上,采用Box-Behnken响应面法进行优化,以挥发油(mL)与β-环糊精(g)的投料比、β-环糊精(g)与水的投料比和研磨时间为考察因素,确定连翘挥发油胶体磨包合的最佳工艺条件。结果:胶体磨研磨法的包合率、包合物得率及综合评分均高于饱和水溶液法和超声法。最佳的包合工艺为挥发油与β-环糊精的投料比为1∶10,β-环糊精与水的投料比为1∶6,研磨时间为20 min。3次试验结果显示,包合率平均值为89.52%,包含物得率平均值为93.98%,综合得分为90.41%,RSD为1.21%。结论:优选的连翘挥发油胶体磨包合工艺操作简便,包合效果好,适合大规模工业化生产。