虎杖研究进展及质量标志物预测

虎杖是我国常用的大宗中药材,资源丰富且分布较广,具有广阔的开发利用前景。虎杖中化学成分类型丰富,包括二苯乙烯、醌、黄酮等类化合物,虎杖的药理作用主要体现在抗炎、抗氧化、抗病毒、抗菌、抗癌、肝保护、心血管保护、免疫调节等方面。在对其化学成分、药理作用综述的基础上,根据中药质量标志物(Q-marker)理论,从生源途径、化学成分有效性、化学成分可测性及不同配伍环境几方面对虎杖Q-marker进行预测分析,为明确虎杖的Q-marker和制定科学的质量标准提供参考。

Qualitative and Quantitative Analysis of Rhizoma of Polygonum cuspidatum

Aim To establish reliable methods for evaluating the quality of rhizoma of Polygonum cuspidatum( Huzhang in Chinese). Methods TLC and HPLC were employed for the chemical identification and content determination,respectively. Results A qualitative TLC method and a quantitative HPLC method with piceid as the reference substance were established, respectively. With piceid as the reference substance and ethyl acetate-methanol-formic acid-water ( 19:3:0.5:1) as the mobile phase, a TLC method for the identification of Huzhang from the commonly used crude drugs of the same family was also set up. Conclusion The established TLC method can reasonably appraise the quality of the drug and easily distinguish Huzhang from the other commonly used crude drugs of the same family. The HPLC method for determining piceid is simple, reproducible, accurate, and feasible.

尖叶走灯藓(Plagiomnium cuspidatum)叶绿素荧光对复合重金属胁迫的响应

利用快速叶绿素荧光动力学技术研究了Cu2+、Zn2+、Cd2+、Pb2+四种重金属离子复合污染下尖叶走灯藓Plagiomnium cuspidatum(Hedw.)T.Kop.叶绿素荧光动力学以及叶绿素含量的变化。结果显示,重金属胁迫导致尖叶走灯藓PSII反应中心的最大光化学效率(Fv/Fm)、光合机构电子传递的量子产额(ETo/ABS)、捕获的激子将电子传递到电子传递链中超过QA的其它电子受体的概率(ETo/TRo)、单位叶面积的反应中心的数量(RC/CSo)降低。重金属胁迫也显著降低尖叶走灯藓植物体叶绿素a、叶绿素b、总叶绿素含量以及Chla/b的值,降低的程度与重金属浓度和胁迫时间有关。尖叶走灯藓可以耐受10μmol/L浓度的复合重金属污染,在10μmol/L浓度范围内,尖叶走灯藓PSII最大光化学效率Fv/Fm、单位面积有活性反应中心的数目RC/CSO、捕获的激子将电子传递到超过QA的其它电子受体的概率ETO/TRO以及用于电子传递的量子产额ETO/ABS等与对照相比均无明显变化,表明在此浓度范围内,重金属不会对尖叶走灯藓的光合器官造成伤害。50μmol/L和100μmol/L浓度的重金属则造成光合系统的不可逆损伤。

基于网络药理学、分子对接及动物试验研究虎杖防治雏鹅痛风的作用机制

为了探讨虎杖防治痛风的潜在作用机制,试验采用网络药理学方法,通过中药系统药理数据库和分析平台(TCMSP)筛选出虎杖的活性成分、作用靶点,通过GeneCards数据库获取痛风的相关靶点;取虎杖与痛风的相交靶点,用Cytoscape 3.8.2软件构建“中药-活性成分-靶点-疾病”网络;用String数据库构建蛋白质-蛋白质相互作用(PPI)关系图,找出关键靶点;对靶点进行KEGG信号通路富集分析,构建“活性成分-靶点-通路”网络;选取关键靶点和主要活性成分,用Autodock 1.5.6软件进行分子对接;建立雏鹅痛风模型,用qRT-PCR检测相关靶蛋白的mRNA表达,验证虎杖的网络药理学分析结果。结果表明:共得到虎杖活性成分10个,作用靶点183个,痛风相关靶点1557个,虎杖防治痛风潜在靶点71个。PPI分析发现关键靶点8个,分别为RELA、MAPK1、Akt1、NFKBIA、TNF、IL-6、MAPK14及HSP90AA1等,主要富集于TNF、NF-κB、Toll样受体、NOD样受体和HIF-1等5条信号通路中。RELA、MAPK1、NFKBIA及TNF等靶点的结合能力较强,能与虎杖中槲皮素、木犀草素稳定结合。虎杖能显著提高痛风雏鹅体重和治愈率(P<0.05),显著降低血清中尿酸和肌酐含量及TNF-α、IL-6、IL-1β等炎症因子水平及肾脏中RELA、TNF及MAPK1等mRNA相对表达量(P<0.05)。说明虎杖可能通过槲皮素、山奈酚等活性成分调控痛风过程中RELA、MAPK1、NFKBIA及TNF等靶点,从而降低炎症因子活性,减轻炎症反应,恢复肾脏功能。

一测多评法测定虎杖药材中6种成分的含量

目的建立一测多评法测定虎杖药材中6种成分的分析方法,并对其进行方法学考察,验证该方法的可行性与准确性。方法以大黄素为内参物,分别建立虎杖苷、白藜芦醇、大黄素-8-O-β-D-葡萄糖苷、大黄素甲醚-8-O-β-D-葡萄糖苷、大黄素甲醚的相对校正因子,计算其他5种成分的含量,用该方法测定不同产地虎杖药材中6种成分含量,同时利用外标法测定各成分含量,测得的结果与外标法测定值进行比较。结果9批不同产地的虎杖中6种有效成分采用一测多评法测得的结果与外标法测定值之间不存在显著性差异,6种成分在测定范围内呈良好的线性关系,平均回收率为98.1%~101.4%,RSD为1.0%~2.3%。结论一测多评法简单快捷,可用于测定虎杖药材中6种成分的含量,可为虎杖药材的质量控制及提取工艺的评价提供参考。

虎杖根不同溶剂提取物的抗氧化活性研究

为探究虎杖根6种不同溶剂提取物的抗氧化活性,利用1,1-二苯基-2-三硝基苯肼(DPPH)自由基清除法、2,2-二氮-双(3-乙基苯并噻唑-6-磺酸)铵盐(ABTS)自由基清除法和总还原力检测法对6种不同溶剂虎杖根提取物进行抗氧化能力评价。选用抗氧化活性较强的95%乙醇提取物进行细胞层面内源性抗氧化能力的研究,评价其对抗氧化基因Nrf2、SOD、CAT、HO-1的调控作用。结果表明,相较于其他5种提取物,95%乙醇提取物的抗氧化能力最强且具有最高的多酚含量。95%乙醇提取物可显著增加Nrf2、SOD、CAT、HO-1等抗氧化基因的表达。95%虎杖根乙醇提取物具有较好的抗氧化活性,具有开发成为天然抗氧化剂的潜力。

虎杖对湿热证2型糖尿病患者的临床疗效

目的探讨虎杖对湿热证2型糖尿病患者的临床疗效。方法140例患者随机分为对照组和观察组,每组70例,对照组给予常规治疗,观察组在对照组基础上加用虎杖颗粒,疗程8周。检测体质量、BMI、血糖指标(FBG、2 h PG、HbA_(1C)、GA)、血脂指标(TC、TG、HDL-C、LDL-C、ApoA-I、ApoB、ApoA、ApoE、sdLDL-C)、肝功能指标(ALT、AST)、脂肪肝程度、TyG、HSI、中医证候评分和疗效变化。结果观察组中医证候总有效率高于对照组(P<0.01),脂肪肝程度更轻(P<0.01)。治疗后,观察组体质量、BMI、FBG、GA、TG、ApoE、TyG、HSI、ALT、中医证候评分降低(P<0.05,P<0.01),并且2 h PG、TyG、HSI、ALT、中医证候评分低于对照组(P<0.05,P<0.01)。结论虎杖可改善湿热证2型糖尿病患者糖脂代谢紊乱,值得临床推广应用。

虎杖苷抗氧化活性研究进展

虎杖苷是从中药虎杖的干燥根茎中提取的单体化合物,是白藜芦醇的葡糖苷衍生物。现代药理学研究发现,虎杖苷在许多生物过程中发挥重要作用,包括氧化应激、炎症和细胞凋亡等。与白藜芦醇相比,虎杖苷因具有更高的抗氧化活性和生物利用度受到广泛关注。近年来研究发现虎杖苷可以显著改善多种氧化应激相关疾病,如神经退行性疾病、糖尿病、心血管相关疾病等。文章就虎杖苷在多种临床常见疾病中的抗氧化作用进行综述,以期为虎杖苷的后续研究及开发利用提供参考。

虎杖多糖中蛋白去除工艺及多糖的抗炎作用研究

目的优化虎杖多糖提取工艺,研究其对RAW264.7细胞活性的影响以及在脂多糖诱导的炎症过程中的作用机制。方法用Sevage法对虎杖多糖粗提取物中游离蛋白进行处理,然后进行单因素实验,最后利用响应面法筛选虎杖多糖提取及除蛋白方案。将RAW264.7细胞分为正常组和不同浓度虎杖多糖组(5、10、20、40、80、120μg·mL^(-1)),采用CCK-8试剂盒检测虎杖多糖对细胞活力的影响。将RAW264.7细胞分为空白组,模型组(100μg·L^(-1)脂多糖),不同浓度给药组(20、40、80μg·mL^(-1)虎杖多糖溶液),采用ELISA试剂盒检测肿瘤坏死因子-α(TNF-α)、白细胞介素-(IL-6)分泌水平;采用Western blot法检测TLR4、MyD88、NF-κBp65蛋白表达水平。结果筛选得虎杖多糖最优提取方案为Sevage试剂与供试液体积比1∶4、振摇强度8档、振摇时间12 min、除蛋白4次。虎杖多糖质量浓度在20~40μg·mL^(-1)内使细胞活力显著提升,对RAW264.7细胞生长有明显促进作用。与空白组相比,模型组细胞活力升高,TNF-α和IL-6分泌水平及TLR4、NF-κBp65和MyD88蛋白表达水平显著升高,表明巨噬细胞炎症模型构建成功。与模型组相比,虎杖多糖20、40、80μg·mL^(-1)组RAW264.7细胞活力显著降低。此外,在细胞上清液中发现TNF-α和IL-6分泌水平明显减少,并且TLR4、MyD88和NF-κBp65蛋白表达水平也显著降低。结论虎杖多糖可以减少脂多糖诱导的RAW264.7细胞中TNF-α和IL-6分泌,抑制NF-κB信号通路可能是其发挥抗炎作用的一种机制。

网络药理学预测黄芩-虎杖抗慢性支气管炎潜在有效成分及作用机制

目的网络药理学预测黄芩-虎杖抗慢性支气管炎(CB)潜在有效成分及作用机制。方法在中药系统药理数据库与分析平台(TCMSP)以黄芩、虎杖为关键词检索潜在的生物活性成分,筛选标准为口服生物利用度(OB)≥30%、类药性(DL)≥0.18。以“慢性阻塞性肺疾病”“慢性支气管炎”为检索词从OMIM和GeneCards数据库中收集经人工确认的CB疾病靶点,检索时限从建库到2024年4月。利用STRING数据库获取蛋白互作(PPI)网络;David数据库进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,利用Cytoscape 3.8.0软件绘制药物-成分-靶点图、成分-靶点-通路图。结果通过TCMSP数据筛选及补充关键化合物,共获得黄芩-虎杖活性成分23个,作用靶点258个;在GeneCards和OMIM数据库检索疾病靶点,删除重复值后得到668个靶点,得到交集靶点80个;PPI网络分析确定TNF、IL-6、JUN、IL-1β、AKT1、VEGFA、TP53、CASP3、IL-10、CXCL8等为核心靶点;GO功能富集分析发现黄芩-虎杖抗CB的生物过程主要涉及炎症反应、氧化应激、细胞凋亡、血管生成和细胞自噬;KEGG通路富集分析发现黄芩-虎杖抗CB的通路可能涉及PI3K-AKT、TNF、IL-17和凋亡信号通路等。反向筛选有效成分结果显示,黄芩中野黄芩苷、汉黄芩素、黄芩苷和虎杖中槲皮素、虎杖苷、大黄素有效成分度值均较高。结论黄芩-虎杖抗CB潜在活性成分涉及野黄芩苷、黄芩苷、汉黄芩素、虎杖苷和大黄素等,作用机制可能通过调控PI3K-AKT、TNF、IL-17和凋亡信号通路,进而减轻炎症反应、改善细胞凋亡,促进细胞自噬发挥治疗作用。

基于高效液相色谱指纹图谱的不同采收期虎杖叶的区分及多成分含量的测定

为研究不同采收期虎杖叶样品的品质差异,进行了题示研究。采收于3~10月的16批样品经烘干、粉碎后,分取0.1 g,加入80%(体积分数)甲醇溶液5 mL,超声45 min,离心10 min,取上清液,过0.22μm滤膜,滤液用高效液相色谱法(HPLC)测定。以不同体积比的乙腈和0.1%(体积分数)磷酸溶液的混合溶液为流动相,在Agilent HC-C_(18)(2)色谱柱上进行梯度洗脱分离。采集16批样品的色谱图,导入相似度评价系统进行相似度分析;以共有成分峰面积为变量,采用主成分分析(PCA)、系统聚类分析和正交偏最小二乘-判别分析(OPLS-DA)等化学模式识别法区分不同采收期的样品;以外标法对鉴定出的9种共有成分进行定量,并分析了这9种成分含量随季节变化的规律。结果显示:16批样品中含有17种共有成分,采收于3月的样品的相似度小于0.800;聚类分析将16批样品分为3类,和PCA分类结果一致;OPLS-DA筛选出5个潜在差异性质量标志物,可用于区分不同采收期样品的质量差异;不同采收期样品中芦丁、槲皮素、虎杖苷等成分随季节变化,二苯乙烯类、蒽醌类化合物在春季时含量最高,黄酮类化合物在秋季含量最高(槲皮素含量在7月达到峰值),酚酸类化合物含量变化较为平稳,可为虎杖叶的质量控制以及采收期的确定提供理论依据。

Optimization of extraction and determination of emodin from Polygonum cuspidatum Sieb. et Zucc. products by HPLC-DAD

A uniform experimental design procedure was used to investigate the effects of some operating parameters on the extraction of emodin from Polygonum cuspidatum Sieb. et Zucc. products. Variables tested were volume ratio of material to solvent, size of material, extraction time and temperature and composition of extraction solvent （mixtures of acetone-water）. Each variable was tested at seven levels; 7 experiments were performed in random order. Analyses of the extracts were performed by high-performance liquid chromatography with diode array detection（HPLC-DAD）. Analytical responses were processed by using a forward regression analysis, in order to find polynomial function describing the relationship between variables and responses. For all the analytes the experimental conditions for providing the highest extraction yield inside the experimental domain considered were found. Finally, a simple, rapid and accurate analytical method was developed for the determination of emodin by high performance liquid chromatography. The separation is achieved within 25 rain on an ODS column using methanol and water as gradient mobiles. Emodin can be quantified by using external standard method detecting at 436 nm. Good linearity is obtained with correlation coefficient exceeding 0.9986 and the detection limit and the quantification limit are 1.53 and 3.23 mg/L respectively. This method shows good reproducibility for the quantification of the emodin with intra-day and inter-day relative standard deviation less than 2.3% and 5.6% respectively. Under optimized extraction conditions, the recovery of the standard is 96.5%. The validated method is successfully applied to quantify the emodin in seven Polygonum cuspidatum sieb. Et zucc. products, which provided an idea for the pre-treatment of determination of active compounds in traditional Chinese medicines.

虎杖中白藜芦醇提取工艺的优化及其抗氧化性

利用单因素和响应面试验考察了超声功率、提取时间、乙醇体积分数和料液比对从虎杖中提取白藜芦醇工艺的影响。利用大孔吸附树脂和反相柱层析联合分离及高效液相色谱对产物进行鉴,并对细胞内外抗氧化性和对紫外照射成纤维细胞的保护作用进行试验。白藜芦醇最佳提取条件为超声功率496W、提取时间33min、乙醇体积分数64%、料液比1∶17,最佳条件下提取率为4.80mg/g,白藜芦醇纯度达99.90%。白藜芦醇为2.5和0.5mg/mL时,DPPH和羟自由基清除率最高,分别为94.92%和94.65%,IC_(50)分别为0.926和0.165mg/mL。白藜芦醇能显著降低紫外照射皮肤成纤维细胞内SOD、CAT、GSH和MDA。

Network Pharmacology Approach to Uncover the Mechanism Governing the Effect of Polygonum cuspidatum on Hepatoma

Background:As a popular Chinese herbal medicine,polygonum cuspidatum is widely used to treat hepatoma in China.Network pharmacology targets biological networks and analyzes the links between drugs,targets,and diseases in these networks.In this study,network pharmacology was utilized to reveal the potential pharmacological mechanisms of polygonum cuspidatum on hepatoma.Methods:The chemical constituents of polygonum cuspidatum were searched from TCMSP data and target gene names were extracted from UniProt database.The GeneCard,OMIM,PharmGkb,Therapeutic Targets database,and DrugBank database were used to establish a database of hepatoma targets.Common targets for drugs and diseases were obtained from Venn online tools.The protein-protein interaction network was constructed with the STRING database to analyze the related protein interaction relationship.The clusterProfiler R software package was used to enrich the common target proteinsof GO and KEGG to obtained the related functions and pathways.Cytoscape 3.7.2 was used to build a“drug-compound-target-disease”network.Finally,docking of the active components with the core target was carried out.Results:Ten active components of polygonum cuspidatum were obtained,and 108 potential targets for hepatoma were identified.The biological functions of the common target genes of polygonum cuspidatum and hepatoma are shown in GO analysis.Pathways involved in the treatment of hepatoma include virus-related signaling pathways,IL-17 signaling pathways,apoptosis signaling pathways,and PI3K/AKT signaling pathways.Conclusions:The network pharmacology directly shows the“drug-compound-target-disease”effects of polygonum cuspidatum on hepatoma,and provides a basis for studying the mechanism of the effect of polygonum cuspidatum on hepatoma.

Discovery of pulmonary fibrosis inhibitor targeting TGF-b RI in Polygonum cuspidatum by high resolution mass spectrometry with in silico strategy

Pulmonary fibrosis(PF)is an irreversible lung disease that is characterized by excessive scar tissue with a poor median survival rate of 2-3 years.The inhibition of transforming growth factor-β receptor type-I(TGF-β RI)by an appropriate drug may provide a promising strategy for the treatment of this disease.Polygonum cuspidatum(PC)is a well-known traditional Chinese herbal medicine which has an anti-PF effect.Accordingly,a combination of high resolution mass spectrometry with an in silico strategy was developed as a new method to search for potential chemical ingredients of PC that target the TGF-β RI.Based on this strategy,a total of 24 ingredients were identified.Then,absorption,distribution,metabolism,and excretion(ADME)-related properties were subsequently predicted to exclude compounds with potentially undesirable pharmacokinetics behaviour.Molecular docking studies on TGF-β RI were adopted to discover new PF inhibitors.Eventually,a compound that exists in PC known as resveratrol was proven to have excellent biological activity on TGF-β RI,with an IC_(50) of 2.211 μM in vitro.Furthermore,the complex formed through molecular docking was tested via molecular dynamics simulations,which revealed that resveratrol had strong interactions with residues of TGF-β RI.This study revealed that resveratrol has significant potential as a treatment for PF due to its ability to target TGF-β RI.In addition,this research demonstrated the exploration of natural products with excellent biological activities toward specific targets via high resolution mass spectrometry in combination with in silico technology is a promising strategy for the discovery of novel drugs.

The Apoptotic Effect of the Methanol Extract of <i>Polygonum cuspidatum</i>through Up-Regulation Death Receptor 5 and CHOP in HSC-2 Human Oral Cancer Cells

Polygonum cuspidatum is used as a traditional medicinal herb for the therapy of various diseases including several types of cancers. In the present study, we focused on addressing the anti-cancer activity and molecular mechanism of methanol extract of Polygonum cuspidatum (MEPC) in HSC-2 human oral cancer cells. The effect of MEPC on oral cancer cells was estimated by 3-(4,5-dimethylthiazol-20yl)-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium (MTS) assay, 4’-6-diamidino-2-phenylindole (DAPI) staining and Western blot analysis. MEPC inhibited the cell viability and induced apoptosis through the induction of death receptor (DR) 5. MEPC also increased the expression of C/EBP homologous protein/growth arrest and the DNA damage-inducible gene 153 (CHOP), a transcription factor induced by ER stress. Thus, we concluded that the induction of CHOP leading to DR5 up-regulation is required for the anti-cancer activity of MEPC in HSC-2 cells and MEPC may be a promising drug candidate for oral cancer.

Effects of compatibility of Scutellaria baicalensis stems and Polygonum cuspidatum on TRPV1 expression and inflammatory cytokines in rats with acute lung injury

Objective:The protective effect of Scutellaria baicalensis Stems and Polygonum Cuspidatum compatibility on lipopolysaccharide(LPS)-induced acute lung injury(ALI)in rats was studied by observing the expression of TRPV1 and inflammatory cytokines.Methods:48 male SD rats were randomly divided into 6 groups:control group,model group,dexamethasone group(5mg/kg)and Scutellaria baicalensis Stems-Polygonum Cuspidatum(3.5,7 and 14g/kg).The administration group was gavaged for 7 days,and the control group and model group were given the same amount of 0.9%sodium chloride.On the 8th day,except the control group,rats in other groups were injected with 8mg/kg LPS through caudal vein to induce Ali model.Take the rat lung tissue 6 hours after modeling,and calculate the wet/dry weight ratio(W/D)of the rat lung tissue;HE staining to observe the pathological changes of lung tissue;Determine the content of tumor necrosis factor-α(TNF-α)and interleukin-1β(1L-1β)in alveolar lavage fluid(BALF)and the activity of superoxide dismutase(SOD)in serum;Detect the mRNA and protein expression levels of TRPV1 receptor in rat lung tissue.Results:Compared with the model group,Scutellaria baicalensis Stems-Polygonum Cuspidatum can significantly reduce the damage of lung tissue structure and bleeding state,W/D value and TNF-α、IL-1βThe content of TRPV1 decreased,the level of SOD increased,and the mRNA and protein expression of TRPV1 receptor decreased.Conclusion:The combination of Scutellaria baicalensis Stems-Polygonum has a protective effect on acute lung injury in rats,and its mechanism may be related to down-regulating the expression of TRPV1 and inhibiting the levels of TNF-αand IL-1βin inflammatory cells.

Chemical composition and pharmacological activities of Polygonum cuspidatum

Polygonum cuspidatum is a traditional Chinese medicine,and its medicinal part is dry rhizome.It is mainly used to treat damp heat jaundice,burns,carbuncle,ulcer poisoning,amenorrhea,and snake bite.Recent studies have found that P.cuspidatum also contains active ingredients against coronaviruses.This paper reviews the chemical constituents and pharmacological activities of P.cuspidatum,so as to provide a scientific basis for the development and utilization of P.cuspidatum resources in the future.

Preliminary Study on Effects of Anthraquinone Extract of Polygonum cuspidatum on KHV

[Objectives]To study the toxic effect and antiviral activity of anthraquinone extract of Polygonum cuspidatum on infection of Koi herpes virus(KHV).[Methods]The MTT method and CPE microscopy were used to detect the common carp brain(CCB)cytotoxicity of the P.cuspidatum anthraquinone extract in 48 h.Eight groups of different concentrations of the P.cuspidatum anthraquinone extract 1.96,3.91,7.28,15.63,31.25,62.5,125,250μg/mL experimental groups and a control group without drug effect were set up.After determining the maximum non-toxic range of the P.cuspidatum anthraquinone extract,the viral replication inhibition test was carried out.[Results]The concentration of the P.cuspidatum anthraquinone extract 31.25μg/mL was recognized as the maximum non-toxic concentration.The survival rate of CCB cells was higher than 80%,and the toxic dose(CC50)of the drug for 50%cell death was(72.67±2.12)μg/mL.The maximum inhibition rate of the P.cuspidatum anthraquinone extract was 78.63%±5.47%at a concentration of 31.25μg/mL,and the 50%effective drug dose(IC50)for inhibiting the virus was(13.67±0.47)μg/mL,and the therapeutic index(TI)was 5.48±0.49.In the direct virus killing test,the highest virus inhibition rate was 32.21%.[Conclusions]Under the experimental conditions,it can be concluded that the P.cuspidatum anthraquinone extract has high anti-KHV activity,and at the same time.It is expected to lay a theoretical foundation for the research of P.cuspidatum anthraquinone extract against KHV.

基于网络药理学探究虎杖治疗非酒精性脂肪性肝炎的作用机制

目的:运用网络药理学探究虎杖治疗非酒精性脂肪性肝炎(Non-alcoholic steatohepatitis,NASH)的主要活性成分及作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology,TCMSP)获得虎杖主要活性成分,于Pubmed compound数据库下载其结构式并导入Pharmmapper数据库获得成分作用靶点;借助Genecards、OMIM、Disgenet等数据库获得非酒精性脂肪性肝炎的疾病靶点;绘制药物-疾病交集靶点韦恩图,Cytoscape 3.9.1软件构建成分-靶点网络;String数据库获得PPI网络并通过拓扑分析得核心靶点网络,于Metascape数据库对潜在靶点进行GO、KEGG富集分析,微生信在线制图平台绘制气泡图及条形图等。结果:经筛选获得虎杖主要活性成分10个,主要活性成分作用靶点436个,疾病靶点3944个;去重结合得疾病靶点。虎杖抗NASH潜在作用靶点81个,6,8-Dihydroxy-7-methoxyxanthone、luteolin、Physovenine等可能为虎杖作用NASH的主要活性成分;PPI网络拓扑分析得到SRC、RXRA、GRB2、AKT1、RXRB、ESR1、STAT1、JAK2、IGF1、IGF1R等10个核心靶点;GO富集分析主要包含生物过程(Biological process,BP)条目1092个、细胞组分(Cellular component,CC)条目49个、分子功能(Molecular function,MF)条目98个,KEGG分析结果130条,涉及调节细胞对脂质的反应(Cellular response to lipid)、细胞内受体信号通路(Intracellular receptor signaling pathway)等生物过程,通过PI3K/Akt等信号通路发挥作用。结论:虎杖可通过多成分、多靶点、多通路对非酒精性脂肪性肝炎发挥治疗作用,其可能涉及抗炎、抗氧化、抗凋亡、调节代谢、抑制细胞增殖等生物活性。虎杖中的多种活性成分如6,8-Dihydroxy-7-methoxyxanthone、luteolin、Physovenine等可能通过SRC、RXRA、GRB2、AKT1等靶点对信号通路进行调控,涉及多种生物过程,从而发挥抗NASH的作用。