Molecular mechanism of treatment of pneumonia in children with Mori cortex-Lycii cortex based on network pharmacology

Objective:To study the molecular mechanism of Mori cortex-Lycii cortex in the treatment of pneumonia in children based on network pharmacology. Methods:TCMSP and BATMAN-TCM online prediction database were used to screen and collect the active ingredients and targets of Mori cortex-Lycii cortex based on oral bioavailability and drug-like. Predictive analysis of disease targets was conducted through PubMed,GeneCards and DrugBank databases. The component-target regulation network was constructed by using Cytoscape 3.7.2 software,and the network topology of the core target was analyzed. Finally,the Bioconductor platform and R language were used for GO function analysis and KEGG pathway enrichment analysis,and the target-key pathway network diagram was constructed. Results:A total of 43 active components,including quercetin,kaempferol,acacetin,and beta-sitosterol,were identified with 242 potential targets. There were 3 271 pneumonia targets in children,among which the key targets were IL-6,AKT1,MAPK8,etc. There were 31 common targets of MMP9,TNF,AKT1 and so on. GO biological processes included the response to lipopolysaccharides,molecule of bacterial origin,metal ions,regulation of apoptotic signaling pathway,and T cell activation. The KEGG signaling pathways involved mainly included TNF,PI3 K/AKT and MAPK signaling pathway. Conclusion:Quercetin,kaempferol,beta-sitosterol and acacetin in Mori cortex-Lycii cortex may act on several signal transduction pathways such as TNF,PI3 K/AKT,MAPK signal pathways through AKT1,MAPK8,IL-6 and MMP9 targets,then treat children pneumonia via antiinflammation action. The results can provide references for the further study on the treatment of pneumonia in children with Mori Ccortex-Lycii cortex.

The Mechanism of the combination of radix paeoniae rubra-cortex moutan in treating cerebral hemorrhage based on network pharmacology

Objective:To clarify the material basis of Chinese medicine pair“Radix Paeoniae Rubra-Cortex Moutan”(Chishao-Mudanpi)and explore their mechanism in the treatment of ICH with network pharmacology.Methods:The active ingredients contained in Radix Paeoniae Rubra and Cortex Moutan were searched and selected based on the oral bioavailability prediction and drug-likeness prediction from the TCMSP database.Then the targets of cerebral hemorrhage were collected from GeneCards,OMIM,and DrugBank databases.After obtained the intersections of drugs and disease,the active component target disease interactive network diagram was drawn by Cytoscape software.The obtained key targets were uploaded to the STRING database for analysis and construct a PPI network map.GO function enrichment analysis and KEGG analysis were performed on the key target proteins.Results:Collected the active ingredients of Radix Paeoniae 119,Radix Paeoniae 55,including paeoniflorin,baicalin,β-sitosterol,etc.Related drug target protein 1190,ICH disease-related genes 823,"Radix Paeoniae-Radix Paeoniae"and 72 common targets of ICH,mainly acting on Akt1,IL6,VEGFA,CASP3,EGF,involving 133 related signaling pathways such as AGE-RAGE,TNF,IL-17,HIF1,PI3K-Akt.Conclusion:The combination of"Radix Paeoniae Rubra-Cortex Moutan"in the treatment of ICH has the characteristics of multiple pathways and multiple targets,which provides a reference and basis for further molecular biology verification in the future.

Study on the Mechanism of Angelica sinensis-Phellodendri Chinensis Cortex in the Treatment of Chronic Prostatitis Based on Network Pharmacology

[Objectives]To explore the mechanism of Angelica sinensis-Phellodendri Chinensis Cortex in the treatment of chronic prostatitis(CP)based on the method of network pharmacology.[Methods]The active components and action targets of Angelica sinensis-Phellodendri Chinensis Cortex were screened by(TCMSP),a systematic pharmacological analysis platform of traditional Chinese medicine,combined with literature search.The target was corrected by Uniprot database,and the disease CP target was screened by GeneCards and OMIM database.The common targets of drugs and diseases were screened by R language software,and the visual network map of drugs-active components-targets-diseases was constructed by Cytoscape 3.5.1 software.The common target protein-protein interaction(PPI)network was constructed by using STRING platform.The R language software was used to annotate and analyze the gene function and pathway of the core target through geneontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG).[Results]46 active components of Angelica sinensis-Phellodendri Chinensis Cortex were screened,and 212 related targets were predicted,of which 159 were related to disease.These targets were mainly involved in biological processes such as heterologous biological stimulation,oxidation and anti-oxidation,and were mainly concentrated in PI3K-Akt,mitogen-activated protein kinase(MAPK),hypoxia inducible factor-1(HIF-1)and other related signaling pathways.[Conclusions]The multi-component,multi-target and multi-pathway action characteristics of Angelica sinensis-Phellodendri Chinensis Cortex were confirmed by network pharmacology,and the possible mechanism of Angelica sinensis-Phellodendri Chinensis Cortex in the treatment of CP was predicted,which provided a theoretical basis for further experiments to verify its action mechanism.

A network pharmacology-based study on the anti-hepatoma effect of Phellodendri Chinensis Cortex

Traditional Chinese medicine(TCM)Phellodendri Chinensis Cortex(PCC)has been used for the treatment of human hepatocellular carcinoma,but the underlying mechanisms are still unclear.In this study,15 active compositions of PCC were obtained from Traditional Chinese Medicine Systems Pharmacology Database(TCMSP),and 505 putative identified targets of PCC were screened by Swiss Target Prediction server.Next,HCC data was downloaded from Drugbank and GeneCards databases.Furtherly,45 common targets were revealed.The network diagrams of the active component-target network,protein-protein interaction(PPI)network and active component-target-pathway network were constructed using Cytoscape software.The analysis of the network results showed that the active ingredients of PCC,such as berberine,obacunone,rutaecarpine,candletoxin A,palmatine,isocorypalmine,quercetin,and(S)-Canadine,had a good binding activity with more targets.Additionally,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses revealed that common targets were significantly enriched in Ras signaling pathway,ErbB signaling pathway,and Mammalian target of rapamycin(mTOR)signaling pathway.Altogether,the multi-component,multi-target,and multi-pathway characteristics of PCC provided a reference for the in-depth study of the mechanism of PCC in the treatment of HCC.

Chemical constituents,biological functions and pharmacological effects for comprehensive utilization of Eucommia ulmoides Oliver

Eucommia ulmoides Oliver is a native plant and valuable tonic Chinese medicine in China with a long history,great economic value and comprehensive development potential.Traditionally,the comprehensive utilization rate of E.ulmoides Oliv.is still very low,only bark has been used as medicine and other parts of Eucommia ulmoides Oliv.cannot be fully utilized,even the leaves have been well utilized in food products in Japan in the past decades.In order to improve the comprehensive utilization efficiency of E.ulmoides Oliv.,in this review,we summarized the varieties and contents of main active compounds,biological functions and pharmacological effects in different parts of E.ulmoides Oliv.The findings suggest that other parts of E.ulmoides Oliv.could replace the bark of E.ulmoides Oliv.to some extent besides of their respective applications.The unique and extensive physiological functions between different parts of E.ulmoides Oliv.indicate that the comprehensive utilization of E.ulmoides Oliv.has a wide space to develop,which is also an effective way to protect E.ulmoides Oliv.resources and improve its the utilization rate.

Network pharmacology prediction and molecular docking-based strategy to investigate the possibility of CPL against myeloproliferative neoplasms

Background:Compound cortex phellodendri liquid(CPL)is a kind of classical compound preparation,which has potential curative effect in treating inflammatory diseases.Increasing evidences support that inflammation plays important roles in the pathogenesis of myeloproliferative neoplasms(MPN).This study aims to preliminarily clarify the therapeutic potential and molecular mechanisms of CPL for MPN based on network pharmacology and molecular docking techniques.Methods:The active components and corresponding action targets of CPL were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),while MPN-related targets were searched through GeneCards,DisGeNET,OMIM,DrugBank and TTD databases respectively.Protein-Protein Interaction(PPI)Networks of potential targets were constructed using STRING 11.5 and analyzed visually with Cytoscape 3.9.1.In addition,Metascape platform was used for GO and KEGG analysis that were subsequently visualized with Cytoscape 3.9.1 built-in plug-ins CluoGO or SangerBox platform.Finally,Autodock Vina was used for molecular docking of potential targets and main active ingredients,which were visualized with Pymol software.Experimentally,we used in vitro mouse primary cells culture system to evaluate the effect of CPL on the erythroid and megakaryocytes differentiation that are excessively driven in MPN respectively.Results:The active components of CPL in the treatment of MPN are mainly flavonoids.The core proteins of CPL for MPN intervention are correlated to TP53,AKT1,JUN,CASP3,EGFR,TNF,MYC,IL6.Multiple signaling pathways were closely related to the treatment of MPN intervened by CPL,including PI3K-Akt signaling,TNF-αsignaling,JAK-STAT signaling and NF-κB signaling pathways.These potential targets had good conformation with the core active ingredients of CPL.In line with above findings,we demonstrated that CPL significantly inhibits the proliferation of differentiation of erythrocytes and megakaryocytes in vitro,further supporting the therapeutic potential of CPL for MPN.Conclusion:This study revealed the active ingredients and potential molecular mechanism of CPL in the treatment of MPN,providing a reference for subsequent basic research.

Exploring the therapeutic effects of Cortex Lycii on essential hypertension

Background:Essential hypertension affects over a billion people worldwide.Despite the absence of a definitive cure,current treatments primarily aim to manage blood pressure levels.There is a compelling need for antihypertensive medications that offer high effectiveness,low toxicity,and minimal side effects.Objective:This study seeks to investigate the antihypertensive properties of Cortex Lycii by employing network pharmacology and validating the findings through molecular docking.Methods:We utilized various platforms and databases related to traditional Chinese medicine to identify the active compounds within Cortex Lycii.Targets associated with hypertension were gathered from well-established disease-related resources.Shared targets were delineated using the EVenn.Subsequently,we conducted GO and KEGG analyses through the DAVID platform and visualized the resultant network with Cytoscape.Molecular docking was carried out using Autodock Vina and PyMOL.Results:Our investigation revealed ten active compounds in Cortex Lycii that demonstrated correlation with 82 essential hypertension-associated targets.These shared targets were categorized into four distinct clusters,each with unique functions.Fourteen hub targets were singled out based on predefined selection criteria.GO analysis unveiled the participation of shared targets in various biological processes linked to hypertension.KEGG analysis identified ten significant signaling pathways associated with hypertension development.Molecular docking analysis provided confirmation of the interaction between the selected hub targets and the active compounds.Conclusion:Cortex Lycii,a traditional Chinese herb with a long history of use,exerts its antihypertensive effects through a combination of active compounds,involvement of multiple targets,regulation of various biological processes,and modulation of key signaling pathways.

白鲜皮免疫调节机制的网络药理学分析及验证

本试验旨在探究白鲜皮的免疫调节能力及其机制。通过TCMSP数据库筛选出11个白鲜皮活性成分,利用GeneCard数据库和OMIM数据库预测到318个相关联的靶点基因,通过对药物靶点的筛选,获得63个疾病与药物共同的靶点。通过Cytoscape软件构建药物-活性成分-靶点网络。使用Perl计算机程序语言对GO功能富集结果进行筛选和KEGG通路富集分析。通过腹腔注射环磷酰胺建立免疫抑制小鼠模型,用1.3、2.6、5.2 g/kg BW(按生药量计)的白鲜皮提取物灌胃免疫抑制小鼠2周后检测小鼠体重、免疫器官指数、血清细胞因子含量、血常规指标。结果显示:白鲜皮中的黄芩素、β-谷甾醇、木犀草素、白鲜明碱、前茵芋碱、槲皮素等化合物通过调节AKT1、IL6、IL1B、JUN、PTGS2、VEGFA等重要靶点,参与调节白细胞介素-17信号通路、肿瘤坏死因子信号通路,进而起到免疫调节的效果。小鼠免疫抑制试验发现,相比模型组,5.2 g/kg BW白鲜皮提取物对小鼠的体重没有产生显著影响(P>0.05),但极显著增加了小鼠的肝脏指数和脾脏指数(P<0.01);此外,5.2 g/kg BW白鲜皮提取物极显著提高了小鼠血清白细胞介素-2(IL-2)、干扰素-γ(IFN-γ)、免疫球蛋白A(IgA)和肿瘤坏死因子-α(TNF-α)含量(P<0.01)。本研究展现了白鲜皮免疫调节多成分、多靶点作用的特点,可为白鲜皮在畜禽健康养殖中的应用提供科学依据。

复方黄柏液涂剂促进Ⅲ度烧伤创面肉芽组织形成的作用机制研究

目的:基于网络药理学和分子对接方法,确定复方黄柏液治疗的Ⅲ度烧伤肉芽组织愈合的有效活性成分、关键靶点和潜在的药理学机制,并进行肉芽组织成纤维细胞的初步验证。方法:从公共数据库中药系统药理学分析平台(TCMSP)检索复方黄柏液组成成分连翘、黄柏、金银花的有效成分和靶点;GeneCards、OMIM数据库检索“Ⅲ度烧伤”疾病相关靶点。通过生物信息学分析,包括蛋白质-蛋白质相互作用(Protein-proteininteraction,PPI)以及基因本体(Gene ontology,GO)和京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析,获得了关键的有效成分、核心靶点和相关信号通路;DiscoveryStudio分子对接分析有效成分化合物与靶蛋白的结合。0.5%的DMSO溶液处理的成纤维细胞记为对照组;槲皮素(40μmol/ml)处理的成纤维细胞记为槲皮素组。采用CCK8法、Transwell实验检测细胞增殖、迁移侵袭;WB试验检测细胞p-PI3K、p-Akt蛋白。结果:共筛选出74个有效成分,331个作用靶点,AKT1为潜在的治疗靶点,木犀草素、山柰酚、槲皮素、汉黄芩素、丹皮酚为潜在的候选药物。PI3K-AKT信号通路可能在复方黄柏液治疗Ⅲ度烧伤中发挥关键作用;分子对接表明槲皮素与AKT1结合最好。与对照组相比,槲皮素组成纤维细胞增殖、迁移侵袭均显著降低,p-PI3K、p-Akt蛋白表达也显著降低(P<0.05)。结论:复方黄柏液促进Ⅲ度烧伤患者肉芽组织形成的生物活性成分为槲皮素,潜在通路为PI3K-AKT信号通路,为复方黄柏液治疗Ⅲ度烧伤的研究提供了思路。

基于网络药理学探讨新疆桑白皮防龋机制及其对主要致龋菌作用的研究

目的探讨新疆桑白皮防龋潜在机制,并分析其对主要致龋菌的作用。方法TCMSP数据库筛选新疆桑白皮活性成分及靶点。Genecards、DisGENET和TTD数据库获取龋病靶点。获取新疆桑白皮防龋的共同靶点,并筛选核心基因。使用DAVID数据平台进行富集分析。采用AutoDock软件进行分子对接验证。通过体外抑菌实验,首先测定新疆桑白皮提取物对变异链球菌、血链球菌、黏性放线菌的50%最低抑菌浓度(50%minimum inhibitory concentration,MIC50)、最低杀菌浓度(minimal bactericidal concentration,MBC),并绘制生长曲线;分别测定新疆桑白皮提取物对变异链球菌、血链球菌、黏性放线菌浮游状态产酸、产糖和黏附能力的影响;通过结晶紫染色法测定新疆桑白皮提取物对主要致龋细菌单菌种50%最低生物膜抑制浓度(50%minimum biofilm inhibition concentration,MBIC50)和50%最低已形成生物膜清除浓度(50%minimum biofilm re-duction concentration,MBRC50),并利用扫描电子显微镜观察生物膜形态。结果筛选出新疆桑白皮防龋关键活性成分包括槲皮素、山奈酚、β-谷甾醇等。肿瘤坏死因子(tumor necrosis factor,TNF)、白细胞介素-6(interleu-kin-6,IL-6)、白细胞介素-1β(interleukin-1beta,IL-1β)等可能是新疆桑白皮防龋的关键靶点。富集分析结果显示新疆桑白皮可能对AGE-RAGE信号通路、IL-17信号通路、TNF信号通路等产生影响。抑菌实验结果显示新疆桑白皮提取物对变异链球菌、血链球菌、黏性放线菌的MIC50分别为0.5、0.5、0.25 mg/mL,MBC分别为4.0、2.0、1.0 mg/mL。新疆桑白皮提取物对3种主要致龋细菌浮游状态产酸、产多糖以及黏附能力的抑制作用较对照组强,差异均具有统计学意义(P<0.05)。新疆桑白皮提取物对变异链球菌、血链球菌、黏性放线菌的MBIC50分别为1.0、1.0、0.5 mg/mL,MBRC50分别为4.0、4.0、2.0 mg/mL。扫描电镜结果显示随着新疆桑白皮药物浓度的增加,生物膜形成量与对照组相比逐渐减少。结论新疆桑白皮可通过槲皮素、山奈酚、β-谷甾醇等活性成分,TNF、IL-6、IL-1β等关键靶点及多种作用途径防龋,不仅能抑制主要致龋细菌浮游状态生长、产酸、产糖、黏附能力且对致龋菌生物膜形成有一定的抑制作用。

中药复方治疗原发性骨质疏松用药规律及作用机制分析

背景:中药复方治疗原发性骨质疏松有着较久的历史,并且疗效确切,但其用药规律及作用机制尚不明确。目的:利用数据挖掘与网络药理学的方法学,探究现代中医家治疗原发性骨质疏松的用药规律、分子层面的作用机制并一定程度的加以验证。方法:将中国知网、万方、维普、PubMed等数据库收录的相关文献作为数据来源,使用Microsoft EXCEL 2019、IBM SPSS 25.0等软件统计和提取相关资料。将数据统计得到的高频药物进行关联规则分析和聚类分析,综合两者结果得到中药复方治疗原发性骨质疏松的核心药物组合,利用网络药理学阐释此组合发挥治疗作用的机制并借助分子对接加以验证。结果与结论:最终纳入151篇文献,筛选出方剂207首,涉及中药285味。①通过上述两种分析综合得到重要药物组合10组,其中置信度和提升度最高的核心药物组合为“骨碎补-杜仲-当归”,其组合治疗原发性骨质疏松的关键成分为槲皮素、山奈酚、柚皮素等,核心靶点为SRC原癌基因(SRC proto-oncogene)、磷脂酰肌醇-3-激酶调节亚单位1(PIK3R1)、RELA原癌基因(RELA)等,主要通路为癌症信号通路、JAK-STAT信号通路、VEGF信号通路、核因子κB信号通路等。②将关键活性成分与核心靶点进行分子对接,两者展示出较好的结合性。③中药复方治疗原发性骨质疏松核心药物组合可利用其多种活性成分,通过多条信号通路、作用于多个靶点发挥疗效,可为后续治疗原发性骨质疏松新药的研发提供理论基础。

基于网络药理学探讨牡丹皮-栀子治疗抑郁症作用机制

目的通过网络药理学的方法研究牡丹皮-栀子治疗抑郁症的作用机制。方法该文通过计算机技术筛选牡丹皮、栀子治疗抑郁症的主要活性成分及其潜在作用靶点,探讨其抗抑郁作用的药理学机制。应用中药系统药理学数据库与分析平台(TCMSP)和Uniport数据库整理及筛选牡丹皮、栀子的有效成分和作用靶点及对应的基因名。通过GeneCards数据库、在线人类孟德尔遗传数据库(OMIM)、靶点预测数据库(TTD)提取抑郁症(depressive disorder,DD)的相关靶点基因。进行Venn分析,将成分靶点与抑郁症疾病靶点取交集,获得共同靶点基因。构建化合物-靶点复合网络,筛选发挥抗抑郁作用的关键成分,同时用共同靶点基因构建蛋白互作网络(PPI)筛选出关键蛋白。将Metascape数据库和微生信云平台筛选得到的共同靶点基因进行京都基因和基因组百科全书(KEGG)与基因本体(GO)通路富集分析,再通过KEGG数据库画出KEGG信号通路图。结果筛选得到牡丹皮、栀子与抑郁症有关的15个活性成分、138个对应靶点;PPI网络涉及138个节点,1648条边;GO富集主要涉及对氧气水平反应、细胞膜筏、DNA结合转录因子活性的调节。KEGG富集气泡图显示与癌症通路、脂质与动脉粥样硬化通路、PI3K-Akt信号通路等相关通路有关。结论通过网络药理学可以分析出牡丹皮、栀子在治疗抑郁症方面的有效化合物和关键通路等,为牡丹皮、栀子治疗抑郁症的临床研究提供了理论依据。

杜仲汤对去卵巢大鼠骨质疏松症的影响及机制研究

目的探讨杜仲汤对去卵巢大鼠骨质疏松症的影响及机制。方法将42只雌性SD大鼠随机分为假手术组、模型组、阳性药组(戊酸雌二醇,0.09 mg·kg^(-1))、谷胱甘肽组(36 mg·kg^(-1))以及杜仲汤低、中、高剂量组(0.54、1.08、2.16 g·kg^(-1))。去卵巢模型大鼠复制成功后,按照设定剂量灌胃给药,灌胃体积为10 mL·kg^(-1),每日1次,连续给药200 d。采用生化试剂盒检测大鼠血清中谷胱甘肽过氧化物酶(GSH)含量;ELISA法检测大鼠血清中抗酒石酸酸性磷酸酶(TRACP)、骨保护素(OPG)含量;骨密度仪检测大鼠股骨骨密度;HE染色法观察大鼠胫骨组织病理变化;Western Blot法检测骨组织中骨形态发生蛋白2(BMP-2)、OPG、一型胶原(COL1)蛋白表达水平;RT-PCR法检测骨组织中BMP-2、Runt相关转录因子2(RUNX2)mRNA表达水平。结果与假手术组比较,模型组大鼠体质量增长值显著升高(P<0.01);血清GSH、OPG的水平显著降低(P<0.05,P<0.01),TRACP水平显著升高(P<0.01);骨密度明显降低(P<0.05);骨小梁结构不完整,出现明显断裂,小梁数稀疏且明显变薄;骨组织中BMP-2、OPG、COL1蛋白表达水平均显著下降(P<0.01),BMP-2、RUNX2mRNA表达水平明显降低(P<0.05)。与模型组比较,杜仲汤低、中、高剂量组大鼠体质量增长值均显著降低(P<0.05,P<0.01),血清GSH水平显著升高(P<0.01),骨小梁结构明显改善,骨小梁变粗,数量增加,骨组织中BMP-2、RUNX2 mRNA表达水平均显著升高(P<0.01);杜仲汤中剂量组大鼠的血清OPG水平显著升高(P<0.01);杜仲汤低剂量组大鼠的血清TRACP水平显著降低(P<0.01),骨组织中COL1蛋白表达水平明显升高(P<0.05);杜仲汤低、中剂量组大鼠的骨密度显著升高(P<0.01),骨组织中OPG蛋白表达水平明显升高(P<0.01);杜仲汤中、高剂量组大鼠骨组织中BMP-2蛋白表达水平明显升高(P<0.05)。结论杜仲汤能提高去卵巢大鼠的骨密度,保护骨小梁完整性,对去卵巢大鼠骨质疏松症有一定防治作用,其机制可能与提高血清GSH、OPG水平,降低TRACP水平,上调BMP-2、OPG、COL1蛋白以及BMP-2、RUNX2mRNA表达,从而促进骨形成有关。

杜仲雄花活性成分的提取、活性机制及质量标志物的研究进展

文章旨在综述杜仲雄花中的主要活性成分及其相关的药理作用机制,进而归纳出可行的质量指标,为工业生产杜仲雄花保健产品的质量评估提供参考,并明确产地和提取加工条件对相关茶饮的活性成分及功效的可能影响。希望该论述能够为杜仲雄花保健食品的研发、工业化生产与创新等提供理论基础和新的思路。

杜仲叶化学成分、药理活性及现代应用研究进展

杜仲叶是一种传统中药,现收录于《中华人民共和国药典》一部,同时其作为一种药食两用中药,具有较高的研究价值和开发潜力。现代研究表明,杜仲叶主要含有黄酮类、酚酸类、木脂素类、环烯醚萜类等化学成分,具有抗氧化、降血压、降血脂、神经保护和骨保护等药理作用。目前已研制和开发出较多以杜仲叶为主药或原料的药品、保健品和食品,在医疗、化工和养殖业等多个领域均有应用。该文通过检索近20年国内外对杜仲叶的相关研究报道,对其化学成分、药理活性和应用进行整理总结,为后续杜仲叶的研究及资源开发提供科学依据。

黄柏炮制历史沿革及其药理作用研究

黄柏作为传统中药之一,具有清热燥湿、泻火除蒸、解毒疗疮之功效,其炮制历史悠久,炮制方法众多。通过查阅历代本草、医学古籍和相关文献资料,对黄柏的历史炮制方法进行整理和归纳,主要包括净制法、切制法和炮制法,其中炮制法分为清炒法和加辅料制法,清炒法有炒、炙、焙、炮、煨、蒸;加辅料的炮制方法分为酒制、盐制、醋制、蜜制、姜制、童便制等多种炮制方法,而现代应用多以酒制黄柏、盐制黄柏为主。同时,对黄柏近年来的药理作用进行总结,主要集中在治抗动脉粥样硬化、抗溃疡、抗痛风、抗肿瘤、降糖、神经保护、止泻、抑菌等方面,以期更深入理解黄柏的药理作用及其内在机制。

杜仲茶的制备工艺及生物活性研究进展

杜仲(Eucommia ulmoides Oliv.)是我国传统中药材,具有2000多年的药用历史。杜仲叶富含环烯醚萜类、木脂素类、苯丙素类、黄酮类、多糖类化合物,以及多种氨基酸、维生素和微量元素等活性成分,已被列入药食同源类目录。杜仲茶是以杜仲叶片或雄花经杀青、揉捻、日晒、发酵、干燥制成的保健型茶饮品。杜仲茶中黄酮类、多酚类等化学成分具有降血脂、降血糖、抗氧化、减肥等功效。总结和比较了杜仲绿茶、杜仲红茶、杜仲黑茶、杜仲烤茶等类型杜仲茶的制作工艺及成分特点,分析了杜仲茶的药理作用机制、香气组分及感官评价。

基于网络药理学和体内实验探究白鲜皮致急性肝损伤的机制

目的通过网络药理学与动物体内实验,探究白鲜皮致急性肝损伤的机制。方法通过TCMSP、TCMIP和SwissTargetPrediction数据库得到白鲜皮的化学成分和作用靶点,GeneCards和CTD数据库获取肝损伤疾病的相关靶点。利用STRING数据库对交集靶点进行蛋白质互作网络分析并筛选出核心靶点,利用DAVID数据库完成GO功能和KEGG通路富集分析,使用Cytoscape软件构建“药物-成分-靶点”多层次关联网络图。动物实验中,通过灌胃给予小鼠92.7 g/(kg·d)白鲜皮,7 d后取材。采用苏木精-伊红(HE)、Masson、油红O染色观察肝脏病理学变化;酶联免疫吸附试验(ELISA)法检测小鼠血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、乳酸脱氢酶(LDH)、肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β的表达情况;实时荧光定量逆转录聚合酶链反应(qRT-PCR)检测肝脏组织蛋白激酶B1(AKT1)、IL-6、TNF-α、肿瘤蛋白p53(TP53)、胱天蛋白酶3(CASP3)、IL-1β的m RNA表达。应用分子对接验证潜在毒性成分与靶点的结合情况。结果通过筛选共得到白鲜皮化学成分14个,预测靶点244个;与肝损伤的交集靶点202个。GO生物过程分析主要涉及基因表达正向调控、凋亡过程的负向调控等。KEGG通路富集分析主要包括癌症途径、磷脂酰肌醇3-激酶-蛋白激酶、TNF、IL-17等信号通路等。病理片结果显示,给予白鲜皮后,HE染色小鼠肝组织中可见重度出血,较大量的肝细胞坏死,核碎裂或溶解;Masson染色显示肝组织出现明显纤维化;油红O染色结果有大量脂滴生成。ELISA结果显示与空白组相比,给药组小鼠血清AST、ALT、ALP、LDH及肝脏MDA、TNF-α、IL-1β水平显著上升(P<0.05),肝脏SOD水平显著降低(P<0.05)。qRT-PCR结果显示给药组小鼠肝脏组织相关m RNA表达量均显著升高(P<0.05)。分子对接显示黄柏酮、白鲜碱、梣酮3个白鲜皮的潜在毒性成分与AKT1、IL-6、TNF-α、TP53、CASP3、IL-1β靶点结合性、亲和力良好。结论黄柏酮、白鲜碱、梣酮、柠檬苦素可能是白鲜皮致小鼠急性肝损伤潜在毒性成分,白鲜皮可能是通过改变AKT1、IL6、TNF-α、TP53、CASP3、IL-1β等蛋白的表达,影响能量代谢、细胞分化、炎症、氧化应激及免疫等多种途径来作用于肝脏,导致肝损伤。

基于网络药理学探讨桑杜防治家禽传染性法氏囊病的作用机制

【目的】本研究运用网络药理学、分子对接和分子动力学模拟方法研究桑叶和杜仲防治传染性法氏囊病(IBD)的作用机制,旨在为防治免疫抑制和传染性法氏囊病的新兽药研发提供思路。【方法】通过中药系统药理学数据库与分析平台(TCMSP)和SwissTargetPrediction数据库收集桑叶和杜仲的活性成分和靶点,利用GeneCards和GEO数据库获得传染性法氏囊病相关靶点。基于Cytoscape 3.7.2软件构建活性成分-靶点网络图。将药物靶点与疾病靶点取交集后得到共同靶点,基于STRING数据库和Cytoscape 3.7.2软件构建蛋白相互作用(PPI)网络图。使用DAVID数据库对交集靶点进行GO功能和KEGG通路富集分析。利用AutoDock 1.5.6和PyMOL软件进行分子对接,使用Gromacs 2020.6软件进行分子动力学模拟。【结果】筛选得到桑叶和杜仲53个有效活性成分,423个潜在作用靶点,5 949个传染性法氏囊病相关靶点,153个交集靶点。PPI显示,关键靶点主要包括白介素-6(IL6)、连环蛋白-β1(CTNNB1)、原癌基因酪氨酸-蛋白激酶(SRC)、IL1B、血管内皮生长因子(VEGFA)等。GO功能和KEGG信号通路富集分析结果显示,桑叶和杜仲可通过对IL18的反应、干扰素-γ(IFN-γ)受体结合、钙信号通路、神经活性配体-受体相互作用等发挥防治传染性法氏囊病的作用。分子对接和分子动力学模拟结果均表明关键活性成分和关键靶点之间具有良好的亲和力,结合稳定。【结论】桑叶和杜仲可能通过槲皮素、去氢双丁香酚、二十碳-11,14,17-三烯酸甲酯、山柰酚、β-谷甾醇等重要活性成分作用于IL6、CTNNB1、SRC、IL1B、VEGFA等关键靶点,通过对IL18的反应、钙信号通路、神经活性配体-受体相互作用等途径发挥对鸡传染性法氏囊病的防治作用。

刘茂才治疗中风病后遗症用药规律的数据挖掘

基于FangNet平台,对全国名中医刘茂才治疗中风病后遗症的有效病案的处方资料进行药物频次、性味归经的统计,并通过分析处方药物的权重等级、药物共现性与互斥性、药物-症状关联规则以及药物聚类,总结刘茂才教授治疗中风病后遗症的用药规律。结果共得到105首处方,涉及95味中药。处方用药以性温、味甘、入肝经的药物为主。挖掘得到17味主药,分别为黄芪、天麻、山茱萸、党参、杜仲、牛膝、川芎、远志、姜黄、石菖蒲、麦冬、白术、丹参、茯苓、钩藤、法半夏、女贞子。药物共现性分析结果得到牛膝-杜仲等12对药对,药物-症状关联规则分析得到天麻-头晕等9组药物-症状关联组合,聚类分析得到4个药物组合。分析结果提示刘茂才教授治疗中风病后遗症用药温和,以扶正补虚的药物为主,常以黄芪、党参大补元气,山茱萸、牛膝、杜仲等补益肝肾,同时兼顾痰瘀同治,攻补兼施。