Hypoglycemic Effect of Forsythia suspensa Leaves on Diabetic Mice

[Objective] This study aimed to investigate the hypoglycemic effect of Forsythia suspensa leaves in diabetic mice. [Method] The model of hyperglycemia mice were obtained by injecting streptozotocin intraperitoneally to study the effect of F. suspensa leaves on lowering blood sugar of hyperglycemia mice and normal ani- mals. [Result] F. suspensa leaves could antagonize the streptozotocin-reducing mice hyperglycemia and significantly reduce the fasting blood glucose level of diabetic mice. [Coaclusion] F. suspensa leaves exhibits a good therapeutic effect on diabetic mice and has a good development prospect.

A Novel Lignan Glucoside from Forsythia suspensa Vahl

从连翘果实中分离得到了五个单体化合物，根据理化性质和光谱分析鉴定为：对－羟基苯乙酸［ｐ－ｈｙｄｒｏｘｙｐｈｅｎｙｌａｃｅｔｉｃａｃｉｄ］（１），（＋）松脂素－β－Ｄ－葡萄糖甙［（＋）ｐｉｎｏｒｅｓｉｎｏｌ－β－Ｄ－ｇｌｕｃｏｓｉｄｅ］（２），（＋）表松脂素－４－β－Ｄ－葡萄糖甙［（＋）ｅｐｉｐｉｎｏｒｅｓｉｎｏｌ－４－β－Ｄ－ｇｌｕｃｏｓｉｄｅ］（３），（＋）松脂素单甲基醚－β－Ｄ－葡萄糖甙［（＋）ｐｉｎｏｒｅｓｉｎｏｌｍｏｎｏｍｅｔｈｙｌｅｔｈｅｒ－β－Ｄ－ｇｌｕｃｏｓｉｄｅ］（４），连翘甙［ｐｈｉｌｙｒｉｎ］（５）。其中３未见文献报道。

A new forsythenside from Forsythia suspensa

A new forsythenside, 4-hydroxy-4-[8-[[1-[（4-hydroxyphenyl）acetyl]-β-D-glucopyranosyl-6-]oxy]ethy1]-2,5-cyclohexadien-1- one, named forsythenside F, was isolasted from the plant of Forsythia suspensa （Thunb.） Vahl. The structure of the new compound was established on the basis of various spectroscopic analysis, including ^1H NMR, ^13C NMR, 2D NMR techniques （HMBC and HSQC）, and HR-ESI-MS.

Establishment and Verification of An Efficient Virus-induced Gene Silencing System in Forsythia

To understand the functional identification of large-scale genomic sequences in Forsythia,tobacco rattle virus(TRV)-mediated virus-induced gene silencing(VIGS),suitable for the plant,was explored in this study.The results showed that the TRV-mediated VIGS system could be successfully used in Forsythia for silencing the reporter gene FsPDS(Forsythia phytoene desaturase)using stem infiltration and leaf infiltrationmethods.All the treated plants were pruned below the injection site after 7–15 d infection;the FsPDS was silenced and typical photobleaching symptoms were observed in newly sprouted leaves at the whole-plant level.Meanwhile,this system has been successfully tested and verified through virus detection and qRT-PCR analysis.After the optimization,Forsythia magnesium chelatase subunit H(FsChlH)was silenced successfully in Forsythia using this system,resulting in yellow leaveswith decreased chlorophyll content.The system was stable,highly efficient and had greater rapidity and convenience,which made it suitable to study the function of genes related to physiological pathways such as growth and development,and metabolic regulation in Forsythia.

The updated weeping forsythia genome reveals the genomic basis for the evolution and the forsythin and forsythoside A biosynthesis

Weeping forsythia (Forsythia suspensa,Oleaceae) is a deciduous broad-leaved tree species distributed in the warm temperate zone of China.However,the species still lacks a chromosome-level genome.In this study,the former draft genome (Accession No.WIPI00000000) of weeping forsythia was assembled into 14 chromosomes with a 712.9 Mb genome size.Weeping forsythia underwent a and b whole-genome duplication events.After the divergence between weeping forsythia and Olea europaea,1 453 gene families had a significant expansion,and 1 146 gene families had a significant contraction.The enrichment pathways and ontologies of expanded genes suggested that the tillering,photosynthesis and growth capacity of weeping forsythia were enhanced after the divergence of weeping forsythia and O.europaea.The contracted genes suggested that the resistance of weeping forsythia to cold and drought was weakened.The last glacial period led to a significant decline in the effective population size of weeping forsythia.Forty-six candidate genes were identified for the synthesis of the forsythin and forsythoside A by genomic and transcriptomic data.In this study,we improved the previous draft genome of weeping forsythia.Our genome will provide genomic resources for the subsequent evolution and breeding research of weeping forsythia.

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.

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.

Three New Compounds from Forsythia Suspensa (Thunb.) Vahl

Three new compounds, suspenolic acid (1), forsythenside A (2), and forsythenside B (3) have been isolated from the fruits of Forsythia suspensa. Their structures were elucidated by spectral methods including IR, H-1- and C-13-NMR, DEPT, H-1-H-1 COSY, H-1-C-13 COSY, NOE difference, HMBC, FABMS, CIMS, and chemical reactions.

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.

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(Forsythia suspensa(Thunb.)Vahl)的试管苗快速繁殖

【目的】连翘是中国常用中草药,也是庭院绿化的常用树种,需求量较大。建立连翘（Forsythia suspensa（Thunb.）Vahl）的试管苗快速繁殖体系,以期为连翘的大规模栽培育种奠定基础。【方法】以MS为基本培养基,添加不同浓度的6-BA与NAA诱导连翘幼茎外植体再生芽的发生;以1/2 MS为基本培养基,添加IAA、IBA或NAA等单一激素,诱导再生芽生根。【结果】结果表明,BA与NAA的比例对于新芽发生有重要影响,NAA的存在通常不同程度导致愈伤组织的发生,当NAA与6-BA比例达到2︰1时,茎段外植体完全脱分化形成愈伤组织。而不含有NAA,即仅含有6-BA单一激素情况下,更有利于芽的发生。对于生根诱导,低浓度IAA或NAA（0.1mg/L）均不能诱导连翘试管苗生根,高浓度（0.5mg/L）会导致茎基部先发生愈伤化,之后才有根从愈伤组织处长出。IBA在0.1~0.5mg/L范围内,均可以诱导90%以上的再生小芽生根。【结论】以连翘的幼茎为外植体诱导连翘的试管苗快速繁殖,MS＋6-BA 0.5 mg/L为最佳的芽诱导培养基;1/2 MS＋IBA 0.2mg/L为最佳的试管苗生根培养基,生根率达到90%以上。

Pharmacokinetic interaction of Forsythia suspensa extract and azithromycin injection after single and co-intravenous administration in rats

Azithromycin and Chinese medicine forsythia are often used together to treat pediatric mycoplasma infections in China. We aimed to investigate the pharmacokinetic interaction of Forsythia suspensa extract and azithromycin after single and co-intravenous administration in rats. Male Sprague-Dawley rats received single(Forsythia suspensa extract or azithromycin) treatment or co-administration of Forsythia suspensa extract and azithromycin. Blood samples were collected at scheduled times, and drug concentrations were determined by HPLC-UV or HPLC-MS/MS methods. Both non-compartmental analyses and nonlinear mixed-effects modeling approaches were applied to fit pharmacokinetic data and evaluate the impact of co-administration. Pharmacokinetic analysis showed that the area under the curve of azithromycin and forsythiaside increased, and clearance decreased significantly(P < 0.05),after co-administration. The in vivo behavior of both azithromycin and forsythiaside could be appropriately described by the two-compartmental model. The final population pharmacokinetic model indicated that co-administration decreased the central volume of azithromycin and forsythiaside clearance significantly. Co-administration of Forsythia suspensa extract and azithromycin significantly decreased the clearance and increased exposure for both drugs. Pharmacokinetic data suggest that drug co-administration may increase efficiency.

A new lignan glycoside from Forsythia suspensa

Phytochemical investigation on Forsythia suspensa(Thunb.) Vahl afforded ten compounds, including five lignan glycosides and five phenylethanoid glycosides. The compounds were isolated by using HP-20 macroporous resin, silica gel, octadecyl silica gel(ODS), size exclusion chromatography resin HW-40 chromatography, and preparative HPLC. The structures were established through application of extensive spectroscopic methods, including ESI-MS, 1D- and 2D-NMR spectroscopy. They were identified as forsythialanside E(1), 8′-hydroxypinoresinol-4′-O-β-D-glucoside(2), 8′-hydroxypinoresinol(3), lariciresinol-4′-O-β- D-glucoside(4), lariciresinol-4-O-β-D-glucoside(5), forsythoside H(6), forsythoside I(7), forsythoside F(8), plantainoside B(9), and plantainoside A(10). Compound 1 was a new lignan glycoside.

连翘生物保鲜剂对冬枣采后链格孢菌的抑菌机理

为了探究连翘生物保鲜剂对冬枣采后链格孢菌的抗菌活性及其机制,通过体外抑菌实验测定最小抑菌浓度(minimum inhibitory concentration,MIC)和最小杀菌浓度(minimum bactericidal concentration,MBC),同时结合连翘生物保鲜剂对链格孢菌细胞成分的释放、细胞膜通透性、胞内酶活力及菌丝形态等的影响,进一步阐明连翘生物保鲜剂对链格孢菌的抑菌机理。结果表明,连翘生物保鲜剂对链格孢菌的MIC是25 mg/L,MBC是100 mg/L;经100 mg/L连翘生物保鲜剂处理后,增强了链格孢菌细胞膜通透性,导致核酸、可溶性蛋白、丙二醛(malondialdehyde,MDA)的含量和相对电导率显著上升;不仅抑制了链格孢菌Na^(+)/K^(+)-ATPase及谷胱甘肽还原酶(glutathione reductase,GR)活力,使其活力分别降低了0.58倍、1.8倍;而且显著降低了麦角甾醇的含量和呼吸抑制率。综上所述,连翘生物保鲜剂对链格孢菌具有良好的抑菌效果,通过破坏链格孢菌细胞膜结构、改变膜通透性、干扰能量代谢等途径发挥抑菌作用。

基于网络药理学及分子对接探讨麻黄连翘赤小豆汤治疗湿热型哮喘与湿疹的作用机制

目的:基于网络药理学及分子对接探讨麻黄连翘赤小豆汤治疗湿热型哮喘与湿疹的作用机制。方法:使用中药系统药理学数据库与分析平台获取麻黄连翘赤小豆汤组方中药的活性成分及其靶点;通过在线人类孟德尔遗传数据库(online mendelian inheritance in man, OMIM)、GeneCards和DisGeNET数据库筛选哮喘和湿疹的相关靶点;取活性成分相关靶点与疾病靶点的交集,得到麻黄连翘赤小豆汤治疗哮喘与湿疹的潜在靶点。使用Cytoscape建立“中药-活性成分-疾病-共有靶点”网络,拓扑分析筛选核心成分。将潜在靶点导入STRING构建蛋白质互作(protein-protein interaction, PPI)网络,并用Cytoscape评估拓扑参数以确定关键靶点。使用DAVID数据库进行基因本体(Gene Ontology, GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)信号通路富集分析。采用AutoDock Vina对核心成分和靶点进行分子对接。结果:麻黄连翘赤小豆汤组方中药活性成分有157个,相关靶点952个。通过GeneCards、DisGeNET和OMIM数据库得到903个哮喘与湿疹的共同靶点。取交集得到麻黄连翘赤小豆汤治疗哮喘及湿疹的潜在靶点143个。“中药-活性成分-疾病-共有靶点”网络拓扑分析显示,刺果甘草查尔酮、荷包牡丹碱、芫花素等为核心成分。PPI网络分析显示,原癌基因酪氨酸蛋白激酶(proto-oncogene tyrosine-protein kinase, SRC)、信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)、白细胞介素-6(interleukin-6,IL-6)为核心靶点。核心靶点主要涉及Th17细胞分化、C型凝集素受体信号通路、松弛素信号通路、T细胞受体信号通路及Th1和Th2细胞分化等生物过程。分子对接显示:核心成分与靶点对接良好,其中荷包牡丹碱与核心蛋白的结合活性最强。结论:麻黄连翘赤小豆汤治疗湿热型哮喘和湿疹具有多成分、多靶点和多通路的特点。

Forsythosides as Essential Components of Forsythia-based Traditional Chinese Medicines Used to Treat Inflammatory Diseases and COVID-19

The dried fruits of the plant Forsythia suspensa(Forsythia Fructus: Lianqiao in Chinese) are used in many herbal preparations to treat various diseases or the associated symptoms. Forsythia extracts contain phenylethanoid glycosides(Ph Gs) such as the forsythosides(Fst A-to-P). The leading products, Fst-A,-B and-F(arenarioside), can be found also in >90 other plants inventoried here. The pharmacological properties of Fst are reviewed, with emphasis on their anticancer, antiviral, and antibacterial activities, which essentially derive from their anti-inflammatory and antioxidant effects. Fst-B functions as a potential binder of the repressor protein Kelch-like ECH-association protein 1(Keap 1), thus promoting the nuclear translocation of the transcription factor Nuclear factor erythroid 2-related factor 2(Nrf2) implicated in the subsequent activation of the production of antioxidant enzymes and repression of the oxidative stress. The regulation of the Nrf2/Heme oxygenase-1 pathway is the central piece of the multifaceted mechanism of action of Fst-A/B. Their prominent antioxidant and anti-inflammatory effects support the use of these compounds in different inflammation-related diseases and conditions, from sepsis to neuroprotection and many other pathologies discussed here. In addition, these properties contribute to the antiviral action of the compounds. Fst-A/B displays activities against the influenza A virus and different Fst-containing traditional Chinese medicinal(TCMs) have revealed beneficial effects to combat the current COVID-19 pandemic. The mechanisms whereby Fst-A/B could inhibit viral multiplication are discussed. Ph Gs likely contribute to the anti-COVID-19 activities reported with several TCM such as Shuang-Huang-Lian oral liquid, Lianhua-Qingwen capsules, and others. This review highlights the pharmacological profile of Fst and illustrates health benefits associated with the use of Forsythia Fructus.

晚花耐寒大果高产连翘品种‘莘翘2号’的选育

目前我国的连翘良种选育研究有待加强,生产中种植的连翘主要来源于野生资源,种类混杂,果实整齐度差,大小不一,产量低而不稳,直接影响到药材质量和经济效益。‘莘翘2号’(Forsythiasuspensa‘Xinqiao No.2’)连翘是野生连翘实生选优中发现的优株,与普通野生连翘相比具有进入结果期早、开花晚、耐寒性强、果实个大、产量高的优点,平均单果质量2.1g,最大单果质量5.6g,定植当年开始结果,第2年平均单株鲜果产量0.5kg,第3~4年进入盛果期,盛果期平均株产鲜果2.2kg;经多年的无性繁殖、集中栽培、苗木推广种植和区域试验,植株生长发育正常,特异性状保持稳定,具有新品种的遗传稳定性和一致性,可作为连翘良种种植发展。

连翘总黄酮提取工艺优化及抗炎活性研究

通过单因素试验和响应面试验设计,评价浸泡时间、料液比、乙醇浓度、提取温度和提取时间对连翘(Forsythia suspensa)总黄酮提取率的影响,建立数学模型,得出二次回归方程,预测连翘总黄酮提取的最佳工艺条件,并对新工艺提取的连翘总黄酮进行小鼠耳廓急性炎症肿胀抑制效果评价,测试连翘总黄酮提取物的抗炎活性。结果表明,最佳工艺条件为料液比1∶20、浸泡时间30 min、提取温度58℃、乙醇浓度60%、提取时间79 min。经验证,新工艺的平均提取率为14.54%。新工艺提取的连翘总黄酮提取液处理二甲苯急性致炎的小鼠耳廓的肿胀值为(15.61±2.73)mg,低于生理盐水处理后的肿胀值(17.21±2.65)mg,体外抗炎试验表明连翘总黄酮提取物可抑制小白鼠耳廓的炎症肿胀。引入浸泡环节的连翘总黄酮提取工艺具有提取率较高、稳定可靠的特点,新工艺提取的连翘总黄酮具有一定的抗炎效果。