Study on mechanism and molecular docking verification of Angelicae Sinensis Radix and Astragali Radix in treating ischemic stroke

Background:Traditional Chinese medicine(TCM)has been shown to be effective in treating ischemic stroke(IS),and the combination of Angelicae Sinensis Radix(ASR)and Astragali Radix(AR)is a core TCM prescription that is widely acknowledged for its efficacy in IS treatment.This study utilized network pharmacology methods to explore the molecular mechanisms underlying the therapeutic effects of Angelicae Sinensis Radix and Astragali Radix in IS treatment,with preliminary validation conducted through molecular docking.Methods:Information on the structure,targets,main biological functions,and pathways of the active components in Angelicae Sinensis Radix and Astragali Radix was collected using databases such as PubChem,PharmMapper,UniProt,and GeneCards.The results were visualized using software such as Cytoscape 3.6.1,Ledock,and pymol.Results:We retrieved 20 active components and 149 targets associated with the compatibility of Angelicae Sinensis Radix and Astragali Radix from various databases,and GeneCards database was used to search 3350 IS-related gene targets,including 78 key targets of Angelicae Sinensis Radix and Astragali Radix for the treatment of IS.Enrichment analysis of these 78 targets using gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)revealed the involvement of 48 GO terms in the treatment of IS,mainly in biological processes such as metabolism,biological regulation,and stress response.The composition of biological devices such as supercavitary membrane,cell fluid,and extracellular space was also involved.The biological functions mainly included protein binding,ion binding,hydrolytic enzyme activity,and others.The identified pathways were estrogen signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,PI3K-AKT signaling pathway,RAP1 signaling pathway,P53 signaling pathway,PPAR signaling pathway,FOXO signaling pathway,RAS signaling pathway,prolactin signaling pathway,HIF-1 signaling pathway,and TNF signaling pathway.Molecular docking analysis showed that the 17 key active components of Angelicae Sinensis Radix and Astragali Radix had strong binding activity with 13 IS key targets.Conclusion:Through the application of network pharmacology methods,it was found that the use of Angelicae Sinensis Radix and Astragali Radix for treating ischemic stroke mainly targets the MAPK and PI3K-AKT signaling pathways,involving several crucial compounds and genes.Nevertheless,additional in vitro and in vivo studies are needed to verify these findings.

Differentiation of human adipose-derived stem cells into neuron-like cells by Radix Angelicae Sinensis

Human adipose tissues are an ideal source of stem cells. It is important to find inducers that can safely and effectively differentiate stem cells into functional neurons for clinical use. In this study, we investigate the use of Radix Angelicae Sinensis as an inducer of neuronal differentiation. Primary human adipose-derived stem cells were obtained from adult subcutaneous fatty tissue, then pre-induced with 10% Radix Angelicae Sinensis injection for 24 hours, and incubated in serum-free Dulbecco＇s modified Eagle＇s medium/Nutrient Mixture F-12 containing 40% Radix Angelicae Sinensis to induce its differentiation into neuron-like cells. Butylated hydroxyanisole, a common in- ducer for neuronal differentiation, was used as the control. After human adipose-derived stem cells differentiated into neuron-like cells under the induction of Radix Angelicae Sinensis for 24 hours, the positive expression of neuron-specific enolase was lower than that of the butylated hydroxyani- sole-induced group, and the expression of glial fibrillary acidic protein was negative. Alter they were induced for 48 hours, the positive expression of neuron specific enolase in human adipose-derived stem cells was significantly higher than that of the butylated hydroxyanisole-induced group. Our experimental findings indicate that Radix Angelicae Sinensis can induce human adipose-derived stem cell differentiation into neuron-like cells and produce less cytotoxicity.

Effect of co-existent components in CO2 supercritical fluid extract of Angelica Sinensis Radix on metabolism of Z-ligustilide after oral administration in rats

Objective:To establish a basis for Angelica Sinensis Radix(ASR)as a dietary supplement for colorectal cancer chemoprevention,the effect of co-existent components in supercritical fluid extract(SFE)of ASR on the pharmacokinetics of Z-ligustilide after oral administration was investigated in vitro and in vivo.Methods:Incubation in gastrointestinal contents and incubation in rat liver tissue homogenates post-mitochondrial supernatant(PMS)experiments were used to study changes in the levels of Z-ligustilide in vitro.Results:Within 4 hours,the level of Z-ligustilide in SFE declined at a slower rate than in its pure form.Clearance of Z-ligustilide after administration in its pure form was significantly slower than that of SFE of ASR(CL,0.96±0.16 mL·min/kg versus 1.24±0.21 mL·min/kg P<0.05;AUC,243.37±16.84 versus 176.69±12.59 mg·min/L).Conclusion:These phenomena may be attributed to the interactions between the co-existent components in SFE of ASR and Z-ligustilide enhancing the stability of Z-ligustilide.These results suggest that the bioavailability of Z-ligustilide in SFE of ASR is improved.However,stabilization of plasma concentration was not sustained,so that the efficacy of active components could not be maintained.Thus,further processing of SFE of ASR is required.

Identification of antidepression constituents from Angelica Sinensis Radix contrubuting to Xiaoyaosan

Aim The study focused on identification and antidepression active verification of constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan based on UPLC-PDA guided isolation technique. Methods The UPLC-PDA chromatogram of Xiaoyaosan was compared with that of Angelica Sinensis Radix. The relative retention time of each peak and the Uhraviolet spectra providing by PDA were used in the analyses. Constituents were isola- ted from Angelica Sinensis Radix under the guidance of UPLC-PDA investigation. Structures of the isolates were elu- cidated by NMR techniques. Anti-depression effect was evaluated on glutamate-induced neurons. Results Five marker peaks of Xiaoyaosan fingerprint were belong to Angelica Sinensis Radix, and they were determined as conife- ryl ferulate（ I）, E-butylidenephthalide （ II）, ligustilide （III）, Z-butylidenephthalide （ IV ）, 14-Acetoxy-12-sene- cioyloxytetradeca-2E,8E,10E-trien-4,6-diyn-l-ol（V）. Compound V was isolated from the plants of Umbelliferae for the first time. Treatment with compound I, III, IV can protect PC12 and SH-SY5Y cell from glutamate-induced cytotoxicity. Antidepression bioactivity of compound I was first investigated. Conclusion UPLC-PDA guided iso-lation technique was confirmed to be a rapid and accurate method to identify the main active constituents from An- gelica Sinensis Radix contrubuting to Xiaoyaosan.

Evaluation of Angelicae sinensis radix as a promising treatmentoption for hyperlipidemia based on network pharmacology

Background: Angelicae sinensis radix has been widely applied in traditional Chinese medicine while little isexplored in its potential mechanism. This study aims to elucidate the effective components and defattingmechanism based on network pharmacology. Methods: Traditional Chinese Medicine Systems PharmacologyDatabase and Analysis Platform was screened to collect the possible active ingredients and their CAS and SMILESwas searched in Pubchem, which further used for reverse molecular docking in Swiss Target Prediction database toobtain potential targets. Hyperlipidemia-related molecules were obtained from GeneCards database, and thepredicted targets of Angelicae sinensis radix for hyperlipidemia treatment were selected by Wayne diagram. Formechanism analysis, the protein-protein interactions were constructed with String, the Gene Oncology enrichmentanalysis and Kyoto Encyclopedia of Genes and Genomes analysis were conducted in DAVID. Results: Usingnetwork-based systems biology analysis, we predicted that 5 active ingredients in Angelicae sinensis radix hasantilipemic effects with 71 potential targets. Through Gene Oncology and Kyoto Encyclopedia of Genes andGenomes analysis, we found that the related signaling pathways mainly involved in arachidonic acid metabolism,and regulation of lipolysis in adipocytes. The related genes are ALOX5, CYP2C19, EPHX2, PTGS1, PTGS2,ADRB1, and ADRB3. Conclusion: Angelicae sinensis radix may alleviate hyperlipidemia through arachidonic acidmetabolism, and regulation of lipolysis in adipocytes. ALOX5, CYP2C19, EPHX2, PTGS1, PTGS2, ADRB1, andADRB3 may be new targets for treatment.

Progress of Radix Astragali and Radix Angelicae Sinensis in the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF)is a chronic,progressive,fibrotic interstitial lung disease.Current treatment options for IPF are limited.Radix Astragali(RA)and Radix Angelicae Sinensis(RAS),according to 5:1 ratio composed of Danggui Buxue decoction(DGBXD),which have played an essential role in the treatment of IPF.This article reviewed the experimental research,clinical research,and progress of RA and RAS(DGBXD)treating IPF to provide a deeper scientific basis for the future experimental research and clinical research.

Potential mechanism of Astragali radix-Angelicae sinensis radix in the treatment of spinal cord injury based on network pharmacology and molecular docking

Objective:Using network pharmacology and molecular docking technology to explore the possible mechanism of Huangqi(Astragali radix)-Danggui(Angelicae sinensis radix)on the treatment of spinal cord injury.Methods:The active components and the targets related to Astragali radix-Angelicae sinensis radix were screened out on the Traditional Chinese Medicine Systems Pharmacology database.Genes of spinal cord injury were searched by Genecards and the Online Mendelian Inheritance in Man databases.The intersection targets between herbs and diseases were obtained through online Venn diagrams.A components-targets-pathways network was established on Cytoscape 3.8.1 software.The STRING database was used to construct the intersection protein interaction network and screen out core targets.Gene Ontology biological processes and enrichment analysis based on the Kyoto Encyclopedia of Genes and Genes of intersection proteins were performed via DAVID database.Finally,the molecular docking with key components and core targets were performed in AutoDock software.Results:The 22 chemical components including quercetin,kaempferol were collected from Astragali radix-Angelicae sinensis radix.It acts on 110 targets,and interleukin-6,tumor necrosis factor,mitogen-activated protein kinase,tumor antigen p53 were considered as the major targets.50 pathways like Interleukin-17 signaling pathway,tumor necrosis factor signaling pathway and mitogen-activated protein kinase signaling pathway participate in biological processes such as positive transcription regulation and lipopolysacchanide response.The molecular docking revealed that the core targets had stronger binding activity with its corresponding active components.Conclusion:Astragali radix-Angelicae sinensis radix has the characteristics of multi-component,multi-target,and multi-pathway effects in treating spinal cord injury.Its potential mechanism may be related to preventing inflammation,improving microcirculation,inhibiting neuronal apoptosis,protecting damaged nerve cells and promoting nerve repair and regeneration.

Hepatic metabolomics combined with network pharmacology to reveal the correlation between the anti-depression effect and nourishing blood effect of Angelicae Sinensis Radix

Angelicae Sinensis Radix(AS)is reproted to exert anti-depression effect(ADE)and nourishing blood effect(NBE)in a rat model of depression.The correlation between the two therapeutic effects and its underlying mechanisms deserves further study.The current study is designed to explore the underlying mechanisms of correlation between the ADE and NBE of AS based on hepatic metabonomics,network pharmacology and molecular docking.According to metabolomics analysis,30 metabolites involved in 11 metabolic pathways were identified as the potential metabolites for depression.Furthermore,principal component analysis and correlation analysis showed that glutathione,sphinganine,and ornithine were related to pharmacodynamics indicators including behavioral indicators and hematological indicators,indicating that metabolic pathways such as sphingolipid metabolism were involved in the ADE and NBE of AS.Then,a target-pathway network of depression and blood deficiency syndrome was constructed by network pharmacology analysis,where a total of 107 pathways were collected.Moreover,37 active components obtained from Ultra Performance Liquid Chromatography-Triple-Time of Flight Mass Spectrometer(UPLC-Triple-TOF/MS)in AS extract that passed the filtering criteria were used for network pharmacology,where 46 targets were associated with the ADE and NBE of AS.Pathway enrichment analysis further indicated the involvement of sphingolipid metabolism in the ADE and NBE of AS.Molecular docking analysis indciated that E-ligustilide in AS extract exhibited strong binding activity with target proteins(PIK3CA and PIK3CD)in sphingolipid metabolism.Further analysis by Western blot verified that AS regulated the expression of PIK3CA and PIK3CD on sphingolipid metabolism.Our results demonstrated that sphingolipid metabolic pathway was the core mechanism of the correlation between the ADE and NBE of AS.

当归不同药用部位的化学成分及药理作用研究进展

当归作为“分根梢”理论的代表药材,其以不同药用部位分别入药起源于唐代,形成于金元,兴盛于明清;经历代医家临床实践总结,逐渐确立了归头止血、归身补血、归尾活血的作用功效。现代研究表明,当归中含有当归多糖、挥发油、有机酸、无机盐等药效部位及阿魏酸、绿原酸、欧前胡素、藁本内酯等药效成分;在当归头、当归身及当归尾等不同药用部位中,上述药效物质基础的种类分布均匀、区别不大,但含量及相关比例差异明显;多数学者认为,含量、比例差异可能是导致当归不同药用部位存在较大药理作用差异的主要原因。通过对相关文献的检索,梳理和总结近年来国内外对当归不同药用部位中药效物质基础分布情况及相关药理作用的研究,从当归不同药用部位中药效物质基础的种类分布和含量差异两个方面综合分析,并结合相关药效物质基础对应的药理作用研究,找寻当归不同药用部位间存在的“成分-效用”关系,以期为历代医家将当归按当归头、当归身、当归尾分别入药提供更强有力的佐证,同时为当归提出进一步研究的主要方向和思路。

丹参-当归治疗缺血性脑卒中作用机制网络药理学研究

目的探讨丹参-当归治疗缺血性脑卒中(CIS)的潜在作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、Swiss TargetPrediction数据库获取丹参和当归的活性成分及作用靶点,并通过检索PubMed、中国知网相关文献进行补充;通过GeneCards、人类孟德尔遗传数据库(OMIM)、DisGeNET数据库获取CIS的潜在靶点;将丹参-当归治疗CIS的共有靶点导入String 11.0平台,构建活性成分与疾病靶点蛋白的蛋白相互作用(PPI)网络,利用Cytoscape 3.8.2软件构建疾病-药物-活性成分-靶点可视化网络;将共有靶点导入DAVID数据库进行基因本体论(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析,并利用Cytoscape 3.8.2软件构建活性成分-核心靶点-通路网络;利用AutoDock软件对疾病-药物-活性成分-靶点网络中度值排名前6的核心靶点和活性成分进行分子对接验证。结果共检索到82种活性成分,其中丹参65个、当归17个,潜在作用靶点787个,疾病靶点671个,共有靶点76个。度值排名前6的活性成分为丹参醇B、丹参新醌D、木犀草素、阿魏酸、藁本内酯、丹参酮ⅡA,核心靶点为MAPK14,MAPK1,AKT1,PTGS2,EGFR,JAK2。共获得GO功能条目2545个,其中生物学过程2244个,细胞组成128个,分子功能173个,分别涉及对脂多糖的反应、膜筏、内肽酶活性等;KEGG信号通路152条,主要涉及PI3K-Akt信号通路、脂质和动脉粥样硬化、钙信号通路等。分子对接结果证明了6种活性成分与其相应核心靶点均有较好的结合活性。结论丹参-当归治疗CIS具有多成分-多靶点-多通路的调控特点,其作用机制可能与抗炎、抗氧化应激、抗神经细胞凋亡、调节自噬功能等有关。

7576张含丹参-当归药对的门诊中药饮片处方回顾性分析

目的:了解江苏省中西医结合医院南部院区/南京市溧水区中医院(以下简称“该院”)含丹参-当归药对的门诊中药饮片处方情况,探究该药对的临床配伍应用规律,为该药对的合理使用提供参考。方法:采用回顾性分析方法,统计2020—2022年该院使用丹参-当归药对的7576张门诊中药饮片处方,对患者的性别、年龄、处方药味数、金额、疗程、涉及科室及病症、使用剂量、常用的配伍比例及配伍饮片等相关内容进行统计分析。结果:7576张含丹参-当归药对的门诊中药饮片处方中,女性患者处方数约为男性患者处方数的3.21倍(5776张vs.1800张),>30~40岁患者居多。单张处方的中药饮片味数多集中在16~20味,开具的疗程均<30 d。丹参的使用剂量为《中华人民共和国药典》规定的10~15 g的处方有6490张,占85.67%;当归的使用剂量为《中华人民共和国药典》规定的6~12 g的处方有6608张,占87.22%。处方数排序居前3位的科室依次为国医堂、妇科及脑病科,治疗的病证以冲任失调、心脾两虚及气滞血瘀证为主。单张处方中丹参用量大于等于当归用量,丹参与当归的配伍比例以1∶1为多,高频配伍饮片为茯苓、川芎、炒白芍。结论:基于处方用药分析,该院含丹参-当归药对的门诊中药饮片处方基本合理,为丹参-当归药对的使用剂量范围及配伍规律研究提供了数据支持,有利于促进临床合理用药。

基于Keap1/Nrf2/HO-1信号通路研究当归醇提物对多囊卵巢综合征大鼠的保护作用

目的使用来曲唑联合高脂饮食建立多囊卵巢综合征(polycystic ovarian syndrome,PCOS)大鼠模型,探讨当归醇提物(ethanol extract of Angelicae Sinensis Radix,EEA)对PCOS大鼠的保护作用及其作用机制。方法来曲唑联合高脂饮食诱导雌性SD大鼠建立PCOS模型,并用EEA干预。阴道涂片染色、HE染色、酶联免疫吸附法(ELISA)和生化指标检测评价EEA对PCOS大鼠的治疗作用,并通过荧光定量PCR(qRT-PCR)和Western blot检测EEA对Keap1/Nrf2/HO-1信号通路的影响。结果阴道涂片和HE染色结果表明,EEA改善了PCOS大鼠动情周期紊乱和卵巢组织病变,ELISA和生化指标检测结果表明EEA可以调节激素紊乱,改善血脂异常;且在模型组中Keap1蛋白和mRNA表达明显上调,Nrf2和HO-1蛋白和mRNA表达明显下调而经过EEA治疗后Keap1蛋白和mRNA表达明显下调,Nrf2和HO-1蛋白和mRNA表达明显上调(P<0.05或P<0.01)。结论EEA可以减轻大鼠PCOS,其机制可能是通过促进Keap1/Nrf2/HO-1信号通路,从而抑制氧化应激。

当归化学成分及药理作用研究进展

当归在补血药中因“补而不滞”的特点,被广泛用于临床。其化学成分主要包括挥发油类、多糖类、有机酸类、氨基酸类、黄酮类等,常用水蒸气蒸馏法、超临界CO_(2)萃取法、有机溶剂萃取法、煎煮法、渗漉法、超声提取等方法进行提取,而炮制方式、地域、物候期、药用部位的不同皆可影响其化学成分。关于当归药理作用的研究亦愈发深入,当前已证实的包括调节血液循环、缺血后损伤保护、抗组织纤维化、镇痛、保护脑和神经、改善机体骨损伤状态、提高机体免疫力等。参考文献76篇。

基于网络药理学及分子对接分析当归-川芎药对治疗银屑病的作用机制

目的:运用网络药理学方法和分子对接技术,预测当归-川芎药对治疗银屑病的潜在分子作用机制。方法:通过中药系统药理学数据库与分析平台筛选出当归和川芎的有效活性成分以及具体的功效靶点,通过检索GeneCards、人类孟德尔遗传综合数据库、DrugBank和DisGeNET数据库,获得银屑病相关靶点。利用Venn网页工具获取药物疾病共同靶点,将其输入Cytoscape 3.9.1软件绘制当归、川芎-共同靶点-银屑病网络图。运用STRING数据库及Cytoscape 3.9.1软件构建蛋白质-蛋白质相互作用网络,通过DAVID数据库进行基因本体(GO)、京都基因与基因组百科全书(KEGG)富集分析,用微生信绘制富集分析的气泡图。利用AutoDock软件对分子对接进行验证,并用PyMOL软件对分子对接进行可视化。结果:获取当归、川芎治疗银屑病的有效活性成分9个,潜在作用靶点28个,关键作用靶点为胱天蛋白酶3、环氧化酶2、雌激素受体1、转录因子AP-1和丝裂原激活的蛋白激酶14。主要涉及药物的反应信号通路、细胞内类固醇激素受体信号通路、磷脂酰肌醇3激酶-蛋白激酶B信号通路和白细胞介素17信号通路等。结论:当归-川芎药对通过多通路、多种有效活性成分和多种有效靶点实现对银屑病的治疗。

不同灭菌方式对当归粉阿魏酸保留率的影响

目的考察不同灭菌方式对当归粉的灭菌效果和有效成分阿魏酸保留率的影响。方法考察湿热灭菌法、干热灭菌法、高温瞬时灭菌法3种方式,对比当归粉灭菌前后的物理性状、微生物数量和阿魏酸保留率的变化。结果当归粉经不同灭菌方式灭菌后,颜色均有不同程度加深,微生物数量均符合规定,阿魏酸均有不同程度损失。而在保证灭菌效果合格的情况下,采用高温瞬时灭菌的当归粉的阿魏酸的保留率最高,可达90.0%以上。结论与湿热灭菌、干热灭菌方式对比,对于含热敏成分阿魏酸的当归粉,采用高温瞬时灭菌方式更具优势。采用高温瞬时灭菌方式,当归粉微生物数量在明显减少至规定限度内的同时,也能最大限度地保留有效成分阿魏酸含量,保证了当归粉的质量。

中心组合设计-响应面法优选当归-川芎饮片苯酞、酚酸类成分提取工艺

目的优选当归-川芎饮片苯酞、酚酸类成分最佳提取工艺。方法在单因素试验基础上,采用中心组合设计-响应面法,以提取时间、乙醇浓度、乙醇用量为影响因素,洋川芎内酯I、洋川芎内酯A、藁本内酯含量及浸膏得率的总评归一值为评价指标,优选当归-川芎饮片苯酞类成分提取工艺;以绿原酸、咖啡酸、阿魏酸含量及浸膏得率的总评归一值为评价指标,优选当归-川芎饮片酚酸类成分提取工艺。结果苯酞类成分最佳提取工艺:加7倍量90%乙醇,每次提取130 min,提取2次;酚酸类成分最佳提取工艺:加7.5倍量65%乙醇,每次提取120 min,提取2次。结论优选的当归-川芎饮片苯酞、酚酸类成分提取工艺稳定、可行,可为后续研究提供依据。

不同前处理方法对5种中药农药残留量检测的影响

目的:研究分析不同前处理方法对当归、菊花、枸杞子、黄芪、金银花中农药残留测定结果的影响。方法:样品分别经QuEChERS法和高速匀浆结合亲水亲油平衡(HLB)材料固相萃取法处理,采用超高效液相色谱-串联质谱法(UHPLC-MS/MS)同时测定克百威、3-羧基克百威、甲拌磷、甲拌磷砜、甲拌磷亚砜、甲基异柳磷等5种农药残留量。采用超高效液相色谱柱Agilent Poroshell 120 SB-C_(18)(2.1 mm×100 mm,2.7μm);采用梯度洗脱方式,水相为含5 mmol·L^(-1)甲酸铵的0.1%甲酸溶液,有机相为含5 mmol·L^(-1)甲酸铵的0.1%甲酸溶液-乙腈(体积比5∶95);柱温为35℃;质谱分析中以电喷雾离子源正离子模式扫描,多反应监测模式检测。结果:QuEChERS法和HLB固相萃取法测得结果偏差在9.09%~55.56%之间。结论:中药农药残留量检测前处理方法的选定,建议以阳性样本的测定数据为评价指标与依据,选择测定值较高、提取效率高的方法。

当归黄芪超滤物通过调控ROS/GSH/GPx4轴抑制铁死亡改善放射性大鼠心肌纤维化

目的探讨ROS/GSH/GPx4轴介导的心肌铁死亡在放射性心肌纤维化中的作用机制及当归黄芪超滤物的干预作用。方法50只大鼠随机分为5组。除空白组外,其余各组大鼠均接受X射线单次局部胸部照射建立放射性心肌纤维化模型。辐射后,当归黄芪超滤物各组大鼠分别灌胃给药30 d后,用小动物超声评价心功能;比色法检测SOD、GSH、MDA及Fe^(2+)活性;免疫荧光检测ROS表达;HE、Masson染色观察病理变化及纤维化;透射电镜观察心肌超微结构;Western blot检测铁死亡及纤维化蛋白表达。结果与空白组比较,模型组LVEF和LVFS值降低;Fe^(2+)、MDA、ROS水平上升,SOD、GSH水平下降;HE及Masson显示有炎性细胞聚集及胶原纤维沉积;透射电镜显示受损线粒体数量增多、排列紊乱,形态不规则、变小、嵴紊乱;Western blot显示α-SMA、Collagen I、NOX1蛋白表达升高,GPx4、FTH1蛋白表达降低;与模型组比较,当归黄芪超滤物组大鼠心功能改善,ROS、抗氧化指标恢复,Fe^(2+)水平降低;线粒体结构及纤维化程度减轻;α-SMA、Collagen I、NOX1蛋白表达下降,GPx4、FTH1蛋白表达上升。结论当归黄芪超滤物对放射性心肌纤维化具有抑制作用,其机制可能是通过调控ROS/GSH/GPx4轴抑制心肌铁死亡发挥作用。

基于网络药理学探讨“黄芪-白术-茯苓-当归”组方治疗糖尿病肾病的作用机制

目的:基于网络药理学探讨“黄芪-白术-茯苓-当归”组方治疗糖尿病肾病(diabetic kidney disease,DKD)的作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)检索黄芪、白术、茯苓、当归的化学成分和作用靶点。借助OMIM数据库检索DKD的靶点,进而获取药物与疾病的交集靶点。采用Cytoscape 3.7.2软件绘制“药物-活性成分-靶点”网络图,并筛选关键成分。利用STRING数据库构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,并筛选核心靶点。通过Metascape数据库对交集靶点进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)分析。结果:“黄芪-白术-茯苓-当归”组方的活性成分44种,其中黄芪20种,白术7种,茯苓15种,当归2种。黄芪靶点413个,白术靶点20个,茯苓靶点26个,当归靶点64个。DKD靶点1024个,疾病与药物的交集靶点19个。槲皮素、刺芒柄花素、山柰酚、异鼠李素可能是关键成分。白细胞介素(interleukin)-6、IL-10、IL-1A、IL-1β、信号传导与转录激活因子1(signal transducer and activator of transcription 1,STAT1)、C-反应蛋白(C-reactive protein,CRP)等可能是核心靶点。GO分析主要涉及血管生成调节、活性氧代谢过程、细胞因子受体结合等。KEGG通路主要包括糖尿病并发症中的AGE-RAGE信号通路、MAPK信号通路、Th17细胞分化、JAK-STAT信号通路等。结论:“黄芪-白术-茯苓-当归”组方可能通过槲皮素、刺芒柄花素等活性成分,调控AGE-RAGE、MAPK等信号通路,作用于IL-6、IL-1A、IL-1β、STAT1、CRP等靶点,从而发挥治疗DKD的作用。

基于网络药理学与分子对接的当归黄芪超滤物改善冠状动脉微血管疾病作用机制

为了探讨当归黄芪超滤物改善冠状动脉微血管疾病的作用机制,利用网络药理学与分子对接检索TCMSP、UniProt数据库筛选当归黄芪超滤物活性成分和作用靶点;通过DisGeNET等数据库得到疾病靶点;利用Venny2.1.0获取交集靶点;使用STRING数据库构建蛋白-蛋白相互作用(Protein-Protein Interaction, PPI)网络;Metascape平台进行GO功能和KEGG通路富集分析,PyMOL对活性成分和关键靶点做分子对接验证.筛选出1 185个药物作用靶点,2 307个疾病靶点,217个交集靶点;获得β-谷甾醇、槲皮素、黄芪甲苷等22个活性成分,得到NLRP3、IL1β、CASP1等61个关键靶点;KEGG分析获得了272条信号通路,包括NOD样受体通路、NF-kappa B通路等.分子对接的最小结合能均<-5.0 kJ·mol^(-1),表明相互对接良好.初步预测了当归黄芪超滤物改善冠状动脉微血管疾病的核心靶点和信号通路,并进行了分子对接验证,为进一步体内外实验提供了思路.