Bioactive constituents and action mechanism of Xiaoyao San for treatment of non-alcoholic fatty liver disease

Xiaoyao San(XYS)is a classic Chinese medicine prescription.It is traditionally used to relieve syndrome of“liver stagnation and spleen deficiency”,a common syndrome type in traditional Chinese medicine,through soothing liver,tonifying spleen,and nourishing blood.Correspondingly,XYS has long application in the treatment of depression,dyspepsia and liver diseases.Given the rising of cutting-edge researches on XYS,there’s a significant need to diligently uncover the bioactive constituents and action mechanisms of XYS for treating non-alcoholic fatty liver disease accordingly.

Suppression of hepatic steatosis in non-alcoholic steatohepatitis model by modified Xiaoyao San formula:Evidence,mechanisms and perspective

In this letter,we comment on a recent publication by Mei et al,in the World Journal of Hepatology,investigating the hepatoprotective effects of the modified Xiaoyao San(MXS)formula in a male rat model of non-alcoholic steatohepatitis(NASH).The authors found that MXS treatment mitigated hepatic steatosis and inflam-mation in the NASH model,as evidenced by the reduction in lipid droplets(LDs),fibrosis markers and lipogenic factors.Interestingly,these hepatoprotective effects were associated with androgen upregulation(based on metabolomics analysis of male steroid hormone metabolites),adenosine 5’-monophosphate-activated protein kinase(AMPK)activation,and restoration of phosphatase and tensin homolog(PTEN)expression.However,the authors did not clearly discuss the relationships between MXS-induced hepatic steatosis reduction in the NASH model,and androgen upregulation,AMPK activation,and restoration of PTEN expression.This editorial emphasizes the reported mechanisms and explains how they act or interact with each other to reduce hepatic steatosis and inflammation in the NASH model.As a perspective,we propose additional mechanisms(such as autophagy/lipophagy activation in hepatocytes)for the clearance of LDs and suppression of hepatic steatosis by MXS in the NASH model.A proper understanding of the mechanisms of MXS-induced reduction of hepatic steatosis might help in the treatment of NASH and related diseases.

Target Prediction of Xinyi San for Rhinitis Based on Network Pharmacology

Objective: To analyze the potential mechanism of Xinyi San in treating rhinitis through network pharmacology. Methods: In the database of Traditional Chinese Medicine Systems Pharmacology (TCMSP), chemical composition and potential targets of Xinyi San were got, and the target genes of rhinitis of Xinyi San were extracted from GeneCards databases. Then we constructed protein-protein interactions (PPI) network of target genes, and then analyzed the Key genes in GO analysis and KEGG analysis. Results: We got 97 components, 53 potential therapeutic targets, 1009 GO items and 92 pathways in our study. The main pathways included Lipid and atherosclerosis, Chemical carcinogenesis-receptor activation, PI3K-Akt signaling pathway, Human cytomegalovirus infection, Prostate cancer, etc. Conclusion: Xinyi San plays a role in treating rhinitis through multiple components, multiple targets and multiple pathways.

The Molecular Mechanism of Xinyi San for the Treatment of Senile Rhinitis Based on Network Pharmacology

Objective: To study the molecular mechanism of Xinyi San for the treatment of senile rhinitis by applying network pharmacological analysis technology. Methods: The effective components and corresponding targets of Xinyi San were collected by TCMSP. The targets of senile rhinitis were collected by the Genecards database. The potential target of Xinyi San in the treatment of senile rhinitis was obtained by Venn analysis. Cytoscape 3.7.2 the software constructs the relationship network model of “disease-single drug-active ingredient-action target”. Protein protein interaction (PPI) network was constructed by using a string database. R4.1.1 software was used for GO function enrichment analysis and KEGG pathway enrichment analysis. Results: In this study, we obtained 158 active ingredients, 40 potential therapeutic targets, 74 GO projects, and 99 pathways. Major pathways include Lipid and atherosclerosis, Chemical carcinogenesis-receptor activation, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Pathways of neurodegeneration-multiple diseases, etc. Conclusion: Xinyi San has the characteristics of multi-component, multi-target, and multi-channel in the treatment of senile rhinitis. This study provides a basis for the in-depth study of Xinyi San.

Discussion on the mechanism of Xiaoyao Wan in the treatment of depression and anxiety based on network pharmacology

In order to clarify the targets of Xiaoyao Wan in the treatment of depression and anxiety,the pharmacological database of traditional Chinese medicine system and the analysis platform(TCMSP)were used to search the chemical components and potential targets of Xiaoyao Wan.The databases of Malacards and Genecards were used to mine the targets related to depression and anxiety.With the help of Cytoscape3.2.1 software,the“Xiaoyao Wan-targets-diseases”network is constructed.The PPI network is constructed through String database.Common targets are enriched by cluster Profiler software package in R language.161 active components of Xiaoyao Wan were screened,and 247 targets related to Xiaoyao Wan were predicted(excluding repetitive targets).The related targets of depression and anxiety were 379,337 respectively.Through the intersection of Venny diagram,24 targets of Xiaoyao Wan,depression and anxiety were obtained.24 key targets were screened out by constructing the interaction network of Xiaoyao Wan,depression and anxiety.Pathway enrichment analysis showed that Xiaoyao Wan mainly acts on key targets involves D(2)dopamine receptor(DRD2),Interleukin-6(IL6),5-hydroxytryptamine receptor 2A(HTR2A),Interleukin-1 beta(IL1B),5-hydroxytryptamine receptor 3A(HTR3A),Sodium-dependent dopamine transporter(SLC6A3),D(1A)dopamine receptor(DRD1),Interleukin-10(IL10),Sodium-dependent noradrenaline transporterin(SLC6A2)and other key targets in the treatment of depression and anxiety,and participates in important pathway processes such as Serotonergic synapse,Dopaminergic synapse,Neuroactive ligand-receptor interaction and regulation of neurotransmitter levels.It is speculated that Xiaoyao Wan plays a role in the treatment of depression and anxiety by affecting neurotransmitters 5-HT and DA,participating in hypothalamic-pituitary-adrenal(HPA)and interfering in the process of inflammation.

Target Prediction of Xinyi San for Nasal Polyposis Based on Network Pharmacology

Objective: To analyze the potential mechanism of Xinyi San in treating nasal polyposis through network pharmacology. Methods: We Screened the active components and targets of Xinyi San by TCMSP database, and disease targets through GeneCards database. We constructed “disease-single drug-component-target” network through software Cytoscape 3.7.2 and constructed PPI network through STRING database. GO function and KEGG pathway enrichment were analyzed to predict its mechanism. Results: We got 162 components, 69 therapeutic targets, 88 GO items and 135 pathways. The main pathways include Lipid and atherosclerosis, Chemical carcinogenesis-receptor activation, Kaposi sarcoma-associated herpesvirus infection, Hepatitis B, Human cytomegalovirus infection, etc. Conclusion: This study preliminarily revealed the active components, targets and pathways of Xinyi San in treating nasal polyposis.

RETRACTED:Exploring the Mechanism of Wu Ling San plus Flavor for the Treatment of Diabetic Macular Edema Based on Network Pharmacology and Molecular Docking Techniques

Short Retraction Notice The paper does not meet the standards of “Chinese Medicine ". This article has been retracted to straighten the academic record. In making this decision the Editorial Board follows COPE's Retraction Guidelines. The aim is to promote the circulation of scientific research by offering an ideal research publication platform with due consideration of internationally accepted standards on publication ethics. The Editorial Board would like to extend its sincere apologies for any inconvenience this retraction may have caused. Editor guiding this retraction: Prof. Maythem Saeed (EiC of CM) The full retraction notice in PDF is preceding the original paper, which is marked "RETRACTED".

The active mechanism of the Sheng Yang San Huo decoction on diabetic peripheral neuropathy on network pharmacology

Objectives:To discuss the mechanism of Sheng Yang San Huo decoction on diabetic peripheral neuropathy using the network pharmacology method.Methods:The BATMAN-TCM database,TCM-ID database,Chinese Natural Product Chemical Composition Database,and TCMIP database were employed to screen the chemical active ingredients of each herb in Sheng Yang San Huo decoction based on the“Libinsky Drug Rules”.SwissTargetPrediction was used to screen effective action targets for each herb in the prescription.Additionally,Cytoscape 3.7.0 was utilized to construct a“drug-target”network.GeneCards,OMIM,and MaLaCards databases were utilized to gather targets related to diabetic peripheral neuropathy.VENNY 2.1 online platform was employed to match drug and disease targets,draw a Venn diagram,and construct a“drug-active compounds-common target”network using Cytoscape 3.7.0.gene ontology biological process analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for the targets were conducted using the DAVID 6.8 database.Enrichment analysis results were visualized using the OmicShareTool online platform.Molecular docking was performed using CB-Dock2.Results:Following screening,a total of 217 active compounds and 132 potential targets were identified in Sheng Yang San Huo decoction.The effects are primarily enriched in pathways such as Lipid and Atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,and the IL-17 signaling pathway.The binding energy of the key active ingredients to the core protein targets of DPN was favorable.Conclusion:The study reveals the characteristics of multiple targets and pathways of Sheng Yang San Huo decoction,providing new insights for the clinical application of this prescription.

Discussion on the mechanism of Xiaoyao Powder in the treatment of irritable bowel syndrome based on network pharmacology

Objective:To predict the key components and potential targets of Xiaoyao Powder in the treatment of irritable bowel syndrome(IBS)and explore its mechanism of action in the treatment of IBS.Methods:The active components and related targets of all compounds of Xiaoyao Powder were obtained by systematic Pharmacological Analysis platform of traditional Chinese Medicine(TCMSP).The related genes of IBS were collected by Genecards and TTD.The network model of"Xiaoyao powder-compound-target-IBS"was established by Cytoscape software.STRING and Metascape platforms were used to analyze drug-disease target protein interactions and conduct network construction and module analysis.Gene Ontology(GO)function enrichment and Kyoto Encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed on the targets.Results:In the end,149 active ingredients,267 potential targets were obtained in Xiaoyao Powder and 1751 IBS-related targets were obtained from the platforms.One hundred and sixty-five related targets were involved in the treatment of IBS by Xiaoyao Powder,among which the key targets were MMP9,VEGFA,EGF,and IL-1B,TNF,IL-6.In the GO function enrichment analysis,1976 entries were obtained for biological processes,210 entries for molecular functions,and 122 entries for cellular components;KEGG pathway enrichment analysis was performed to obtain PI3K-Akt pathway,AGE-RAGE signaling pathway,Calcium signaling pathway.Conclusion:Xiaoyao Powder may treat IBS by strengthening intestinal barrier function,reducing visceral sensitivity,inhibiting oxidative stress and inflammation.

The Efficacy and Safety of Modified Xiaoyao San for Perimenopausal Syndrome (PMS): A Systematic Review and Meta-Analysis

Objectives: To assess the efficacy and safety of modified Xiaoyao San (XYS) for treating Perimenopausal syndrome (PMS). Methods: Literature searches were carried out on PubMed, Cochrane Library, CNKI Database, Chinese Biomedical Literature Database, Wan Fang Database, and VIP Database up to December 2018. Hand search for further references was conducted. Study selection, data extraction, quality assessment, and data analyses were performed as request of the Cochrane standards. Results: Nine publications in total were suitable for inclusion. There was evidence that modified XYS was tested to be more effective in improving overall symptoms compared with HRT (odds ratio 3.50, 95% CI 2.56 to 4.78). Whereas HRT was more sensitive and direct in decreasing FSH (WMD 6.69, 95% CI 5.60 to 9.52) and LH (WMD 7.00, 95% CI, 5.75 to 8.25) in comparison with XYS group. It was also strongly supported that XYS had less adverse effect than HRT (odds ratio 0.07, 95% CI 0.05 to 0.10). Conclusion: Modified XYS might be more effective and safer in treatment of perimenopausal syndrome. However, due to poor methodological quality in the majority of included studies, the potential benefit and safety about XYS need to be confirmed in rigorously designed, multi-centre, and large-scale trials.

Novel insights into the effect of Xiaoyao san on corticosterone-induced hepatic steatosis:inhibition of glucocorticoid receptor/perilipin-2 signaling pathway

Objective:Xiaoyao san(XYS)is a classic traditional Chinese medicinal formula.It has been clinically administered to regulate liver function.However,its mechanisms in glucocorticoid-induced hepatic steatosis are unknown.This study aimed to investigate whether XYS protects against corticosterone(CORT)-induced hepatic steatosis,and to explore its mechanism.Methods:High-fat diet mice induced with hepatic steatosis by 2mg/kg CORT were administered 2.56 g/kg or 5.12 g/kg XYS daily for 7 weeks.The effects of XYS on hepatic steatosis in mice were evaluated by H&E and Oil Red O staining and by measuring their plasma lipids(triglyceride,total cholesterol,and free fatty acids).The mechanism of XYS against hepatic steatosis was investigated by network pharmacology,immunohistochemistry,western blotting,and gain-of-function/loss-offunction experiments.Results:XYS alleviated CORT-induced steatosis,decreased plasma lipids,and inhibited glucocorticoid receptor(GR)activation in the liver.Network pharmacology data indicated that XYS may have mitigated hepatic steatosis via GR which mediated adipose differentiation-related protein(ADFP).Gain-of-function/loss-of-function experiments in vitro confirmed that GR positively regulated ADFP expression.Conclusions:XYS ameliorated CORT-induced hepatic steatosis by downregulating the GR/ADFP axis and inhibiting lipid metabolism.Our studies implicate that XYS is promising as a therapy for CORT-induced hepatic steatosis,and lay the foundation for designing novel prophylactic and therapeutic strategies on CORT-induced hepatic steatosis.

Effect of Xiaoyao San on the brain-gut axis in rats after chronic immobilization stress

Objective:To investigate the effect of Xiaoyao San on the brain-gut axis in rats exposed to chronic immobilization stress (ClS).Methods:Rats were divided into control,model,and treatment groups.The rats belonging to the model and treatment groups were subjected to CIS for 21 consecutive days,during which they were administered Xiaoyao San decoction [3.854 g/(kg· d)] or vehicle by gavage,and their body weight gain,food intake and water intake were monitored.The rats were subsequently subjected to the open field test (OFT) and D-XyloSe absorption test,and the expression levels of neuropeptides secreted by the hypothalamus and stomach were determined by enzyme-linked immunosorbent assay (ELISA),radioimmune analysis,or real-time fluorescence quantitative polymerase chain reaction.Gastric mucosal morphology was also assessed.Results:The model rats exhibited complex brain-gut axis abnormalities following exposure to CIS,abnormalities signified by decreases in food intake,reductions in digestive absorption,decreases in body weight,decreases in the total distances traveled and increases in the time in the central zone during the OFT,gastric mucosal lesion development and decreases in gastrointestinal hormone secretion.These changes were reversed after treatment with Xiaoyao San,which also regulated the secretion of both peripheral (serum and stomach) and central (hypothalamus) brain-gut peptides.Specifically,the levels of neuropeptide Y (NPY) and neuropeptide Y receptor Y5,which are secreted by the hypothalamus and promote digestive function,were increased in the Xiaoyao San-treated group compared with the model group.Furthermore,the levels of pro-opiomelanocortin (POMC) and its receptor,melanocortin-4 receptor (MC4R),which are secreted by the hypothalamus and inhibit digestive function,were significantly decreased in the treatment group compared with the model group.However,the levels of ghrelin (GHRL),gastrin (GAS) and motilin (MTL),which are secreted by the stomach,were significantly increased in the serum and stomach of the treatment group compared with the serum and stomach of the model group following Xiaoyao San treatment (P <.05 vs.the model group).Conclusion:Xiaoyao San attenuates CIS-induced gastrointestinal dysregulation by regulating the peptides secreted by both the hypothalamus and the gastrointestinal tract (GIT),suggesting that its effects are associated with the brain-gut axis.

加味逍遥散通过外泌体miRNA途径发挥抗肝癌作用

背景:在课题组先前研究中发现加味逍遥散具有明显的抗肝癌作用,但具体作用机制不明。目的:基于高通量测序结合生物信息学,探讨加味逍遥散对二乙基亚硝胺慢性诱导的原发性肝癌模型大鼠血浆外泌体miRNA水平的调节作用。方法:将SD大鼠随机分为空白对照组、肝癌模型组、加味逍遥散组。以二乙基亚硝胺持续给药12周诱导肝癌模型,从第17周开始,加味逍遥散组大鼠给予加味逍遥散灌服,每日1次,直至第20周末停药,空白对照组和肝癌模型组大鼠给予等量生理盐水灌胃,通过检测大鼠肝组织的形态结构、肝癌标志物Glypican-3蛋白和血清甲胎蛋白表达验证抗肝癌效应。使用超速离心法分离提取各组大鼠血浆外泌体,利用高通量测序技术筛选出大鼠血浆外泌体中差异表达的miRNA,生物信息学预测加味逍遥散通过肝癌血浆来源外泌体miRNA发挥抗肝癌作用的潜在生物标志物,并进行功能分析。结果与结论:①加味逍遥散对肝癌模型大鼠肝组织的形态结构有显著改善作用,与肝癌模型组相比,加味逍遥散组肝癌标志物Glypican-3蛋白和血清甲胎蛋白的表达均显著降低;②生物信息学分析显示,加味逍遥散组对肝癌模型组上调的miR-223-3p与基因E2F1、NCOA1存在靶向结合位点,并且与肝癌生存率及预后密切相关。由此可见,加味逍遥散对肝癌有治疗作用,可能是通过肝癌血浆来源外泌体miR-223-3p靶向负调控NCOA1/E2F1进而发挥抗肝癌效应。

基于肝脏蛋白质组学探讨加味丹栀逍遥散的抗抑郁作用及机制

[目的]探讨加味丹栀逍遥散对慢性不可预知性温和应激(CUMS)抑郁小鼠模型的干预作用及可能机制.[方法]C57BL/6N小鼠分为正常组、模型组、加味丹栀逍遥散组和氟西汀组.采用CUMS复制抑郁模型,模型成功后灌胃给药4周.末次给药后进行行为学测试,采用串联质谱标签法(TMT)蛋白质组学分析小鼠肝脏差异蛋白的表达谱,通过Kyoto encyclopedia of genes and genomes(KEGG)通路富集加味丹栀逍遥散抗抑郁的相关通路和蛋白;血液生化检测总胆固醇及总胆汁酸含量.[结果]与正常组相比,模型组小鼠糖水偏好率下降,自主活动次数减少,加味丹栀逍遥散给药后上调小鼠糖水偏好率及自主活动次数.蛋白组学结果显示模型组与加味丹栀逍遥散给药组之间肝脏差异表达蛋白20个,其中上调11个,下调9个.KEGG通路富集分析发现差异表达蛋白主要参与了胆固醇代谢、初级胆汁酸的合成等.生化检测发现,与正常组相比,模型组总胆固醇含量下降而胆汁酸含量升高,加味丹栀逍遥散给药能显著增加总胆固醇含量而减少总胆汁酸含量.[结论]加味丹栀逍遥散具有良好的抗抑郁效应,其机制可能与调节肝脏胆固醇异常代谢、降低血液总胆汁酸有关.

逍遥散联合水飞蓟素胶囊治疗肝郁脾虚证非酒精性脂肪性肝病临床研究

目的:逍遥散联合水飞蓟素胶囊治疗肝郁脾虚证非酒精性脂肪性肝病(NAFLD)的疗效。方法:选取90例肝郁脾虚证NAFLD患者,按随机数字表法分为对照组及治疗组各45例。2组行非药物措施,对照组予以水飞蓟素胶囊口服,治疗组在对照组基础上加逍遥散治疗。2组均连续治疗12周。比较2组临床疗效,比较2组治疗前后肝功能指标[谷草转氨酶(AST)、丙氨酸转氨酶(ALT)、谷氨酰转肽酶(GGT)]值、血脂指标[总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]值、血清TLR4/NF-κB信号通路相关蛋白水平[血清TOLL样受体4(TLR4)、髓样分化因子88(MyD88)、核转录因子-κB(NF-κB)]、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的变化。结果:治疗12周后,治疗组临床疗效总有效率为91.11%,对照组为73.33%,2组比较,差异有统计学意义(P<0.05)。治疗12周后,2组AST、ALT、GGT指标值均较治疗前下降(P<0.05),治疗组上述3项指标值均低于对照组(P<0.05)。治疗12周后,2组TC、TG、LDL-C水平均较治疗前下降(P<0.05),HDL-C水平均较治疗前上升(P<0.05);治疗组TC、TG、LDL-C水平均低于对照组(P<0.05),HDL-C水平高于对照组(P<0.05)。治疗12周后,2组血清TLR4、MyD88、NF-κB、IL-6、TNF-α水平均较治疗前下降(P<0.05),治疗组上述5项水平均低于对照组(P<0.05)。结论:逍遥散联合水飞蓟素胶囊对肝郁脾虚证NAFLD的疗效确切,可有效改善肝功能及血脂状况,调节血清TLR4-NF-κB信号通路,抑制炎症反应。

基于网络药理学和实验验证分析逍遥散治疗黄褐斑作用机制研究

目的基于网络药理学技术及实验验证分析逍遥散治疗黄褐斑的作用机制。方法应用TCMSP等数据库和相关的文献资料,检索逍遥散的生物活性成分及相关作用靶点,构建逍遥散的药物-有效成分-作用靶点网络。基于Drugbank和Genecards等数据库建立与黄褐斑相关的疾病靶点,与逍遥散的有效成分靶点匹配获得潜在治疗靶点。根据Metascape数据库和DAVID数据库对潜在的治疗靶点进行GO生物过程、KEGG信号通路和蛋白质-蛋白质相互作用(PPI)分析,PPI网络的拓扑分析用Cytoscape软件进行。并用实验验证上述结果。结果逍遥散中有效化学成分有928种,包括白芍85种,白术55种,柴胡349种,当归125种,茯苓34种,甘草280种,有效成分作用靶点基因155个。在药物-有效成分-靶点网络内重要性前10的有效成分中,来源自柴胡4种,白芍3种,白术1种,甘草2种。共收集到49个黄褐斑相关疾病靶点,其中有24个是逍遥散治疗黄褐斑的潜在靶点基因。KEGG富集分析表明,在全部的20调信号通路中得到10条较为靠前的信号通路。GO功能富集分析显示,前10个生物过程包括分子调节功能、磷酸化等;前10个分子功能包括细胞传递部分、生物膜等;前10个细胞定位包括核苷酸、嘌呤核苷酸等。PPI网络经提取后获得了包含36个节点的核心网络,其中HSP90AA1、HSP90AB1、NTRK1、CUL3、APP、EGFR、TP53、UBC、MCM2、PRKACA基因是核心靶点。实验验证表明,逍遥散可显著改善大鼠黄褐斑情况;能升高血清SOD水平,降低血清Tyr和MDA含量;改善黄褐斑处皮肤组织结构和皮肤HMB45表达情况。结论逍遥散可通过多成分、多靶点和多通路治疗黄褐斑,起治疗作用的有效成分主要来源自柴胡、白芍、白术和甘草,而核心靶点主要有HSP90AA1等基因。

黄芩咳喘散治疗支气管哮喘临床研究和网络药理学效应机制探讨

目的基于网络药理学研究黄芩咳喘散防治支气管哮喘的有效性及其效应物质探讨。方法选取符合纳入标准的患者共94例,随机分为治疗组和对照组各47例。所有患者均接受常规药物治疗。治疗组给予黄芩咳喘散三伏贴,对照组给予其模拟剂三伏贴。对比两组患者治疗前后中医症候积分评分情况、ACT评分、半年内疾病发作次数、血清嗜酸性粒细胞(EOS)等情况。基于网络药理学和分子对接等探讨黄芩咳喘散与支气管哮喘可能的效应物质及作用机制。结果数据显示:①治疗组患者临床治疗总有效率高于对照组(P<0.05);②治疗组患者咳嗽气促、喘息咯痰、食少便溏、神疲乏力单项症状评分、ACT评分、半年内疾病发作次数均低于对照组(均P<0.05);③两组患者EOS水平均降低,且治疗组各指标值明显低于对照组(均P<0.05);④网络药理学筛选黄芩咳喘散有效活性成分潜在作用靶点与支气管哮喘的交集靶点26个,关键有效成分包括四羟基黄酮、亚油酸乙酯、棕榈酸等,涉及核心靶点包括SIRT1、STAT3、ESR1、PPARA等,可能涉及免疫、脂肪酸代谢、激素类反应、细胞坏死因子反应等生物过程。⑤分子对接显示黄芩咳喘散中有效活性成分四羟基黄酮(5,7,2′,6′-Tetrahydroxyflavone)通过氢键分别与支气管哮喘关键靶点SIRT1的氨基酸ILE411、GLU410、LYS408、SER370、LYS375,与STAT3的氨基酸ASP334、LYS574,与ESR1的氨基酸LEU346及PPARA的氨基酸MET320、LEU331、THR334结合。结论黄芩咳喘散治疗支气管哮喘肺脾气虚证患者具有可靠的临床疗效,在改善临床症状、减少疾病发作次数等具有积极作用。经网络药理学分析黄芩咳喘散可能通过SIRT1、STAT3、ESR1等靶点作用于PI3K-Akt、JAK-STAT、NF-κB等通路从减轻气道炎症反应、抑制气道重塑等方面发挥治疗作用,进一步分子对接后提示该药的有效活性成分四羟基黄酮与哮喘疾病靶点SIRT1、STAT3、ESR1及PPARA具有良好的结合能力。

基于网络药理学和分子对接探讨槲芪散治疗原发性肝癌作用机制

目的:基于网络药理学和分子对接技术探讨槲芪散治疗原发性肝癌的作用机制。方法:通过中药系统药理学数据库和分析平台(TCMSP)数据库获取槲芪散的活性成分,利用GeneCards、OMIM及PharmGkb数据库筛选原发性肝癌相关基因,并采用R软件获取药物-疾病交叉靶点。采用Cytoscape3.7.2软件对药物-疾病交叉靶点与活性成分进行槲芪散活性成分-靶点-原发性肝癌网络构建,筛选出核心成分。采用STRING平台对于药物-疾病交叉靶点进行蛋白质–蛋白质相互作用(PPI)网络分析,通过MCODE插件进行聚类分析以获得与原发性肝癌患者预后相关的关键靶点,并通过TCGA数据库的原发性肝癌队列对关键靶点进行预后分析。采用R语言软件包对作用靶点进行基因本体论(GO)生物功能分析和京都基因和基因组百科全书(KEGG)通路富集分析,并利用AutoDock Vina1.1.2软件对主要活性成分与关键靶点进行分子对接验证。结果:共筛选出槲芪散活性成分113个,作用靶点226个,1765个疾病靶点,预测得到116个抗原发性肝癌靶点。槲芪散治疗原发性肝癌的关键成分有槲皮素、山柰酚、木犀草素、柚皮素、丹参酮ⅡA等。PPI网络显示,雌激素受体1(ESR1)、半胱氨酶蛋白酶3(CASP3)、肿瘤蛋白53(TP53)、B细胞淋巴瘤2(BCL2)、信号转导与转录激活因子3(STAT3)、丝裂原活化蛋白激酶3(MAPK3)、细胞周期蛋白D1(CCND1)、丝裂原活化蛋白激酶1(MAPK1)、Fos原癌基因(FOS)、蛋白激酶B1(AKT1)和热休克蛋白90α家族A成员1(HSP90AA1)为槲芪散治疗原发性肝癌的关键靶点。预后分析显示,ESR1、CASP3、MAPK3、AKT1以及HSP90AA1的表达与原发性肝癌患者的生存时间密切相关。富集分析揭示,槲芪散主要富集在化学应激的细胞反应、活性氧化物的反应、脂多糖的反应以及对异物刺激的反应等细胞过程中发挥作用,能够调控磷脂酰肌醇-3-激酶-蛋白激酶B(PI3K-AKT)信号通路、白细胞介素-17(IL-17)信号通路及肿瘤坏死因子(TNF)信号通路等多条信号通路发挥治疗作用。分子对接显示,关键靶点TP53、AKT1、STAT3、ESR1、MAPK1与柚皮素、山柰酚、槲皮素以及木犀草素能够稳定结合。结论:槲芪散中的柚皮素、山柰酚、槲皮素及木犀草素等成分能够作用于AKT1、ESR1、CASP3、MAPK3等多靶点,通过调控PI3K-AKT信号通路、IL-17信号通路等发挥治疗原发性肝癌的作用。

基于UHPLC/Q-Orbitrap-MS的石决明散化学成分鉴定及降压作用网络药理学研究

[目的]基于入血成分分析和网络药理学探讨石决明散(SJMS)抗高血压(HT)的潜在作用机制。[方法]利用超高效液相色谱-四级杆/静电场轨道阱高分辨质谱联用(UHPLC/Q-Orbitrap-MS)技术对SJMS中的主要化学成分和入血成分进行定性分析,利用SEA和SwissTargetPrediction数据库预测入血成分的作用靶点;借助GeneCards和DrugBank数据库获得HT的相关靶点;通过String平台和Cytoscape软件对SJMS抗HT的潜在靶点进行PPI网络构建;使用DAVID数据库对交集靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)代谢通路富集分析;最后采用Cytoscape软件构建“成分-疾病-通路-靶点”网络图分析。[结果]方剂共鉴定出129个主要化学成分和23个原型入血成分;获得SJMS抗HT的交集靶点共296个,其中SRC、TP53、STAT3、EGFR、AKT1、ESR1等是SJMS抗HT的关键作用靶点;橙黄决明素、红链霉素-6-O-β龙胆二糖苷、决明柯酮、甘草次酸、新绿原酸、甘草酸、芹菜素等为SJMS抗HT的主要活性成分;GO富集到基因功能30个条目,差异具有统计学意义(P<0.01),SJMS抗HT与蛋白质磷酸化、凋亡过程的负调控、细胞增殖的正向调节等有关;KEGG通路共20条,差异具有统计学意义(P<0.01),结果显示:SJMS主要通过缺氧诱导因子-1(HIF-1)信号通路、高级糖基化终末产物-受体(AGE-RAGE)信号通路等来发挥治疗HT的作用。[结论]研究初步阐明了SJMS的潜在药效物质基础,探讨了SJMS抗HT的潜在作用机制,为其临床应用提供了一定的理论参考。

基于网络药理学及分子对接探讨四逆散对溃疡性结肠炎与抑郁症“异病同治”的作用机制

目的 基于网络药理学及分子对接探讨四逆散对溃疡性结肠炎与抑郁症“异病同治”的作用机制。方法 利用TCMSP数据库获取四逆散的潜在活性成分及其相关作用靶点;利用GeneCards、CTD、TTD数据库筛选溃疡性结肠炎和抑郁症的疾病相关靶点;对上述预测得到的活性成分作用靶点与疾病相关靶点取交集,获得四逆散治疗溃疡性结肠炎和抑郁症的潜在作用靶点(共有靶点),采用Cytoscape 3.7.2软件构建“中药-活性成分-疾病-共有靶点”网络,分析核心成分;将共有靶点导入STRING数据库,构建共有靶蛋白相互作用(PPI)网络,分析关键靶点;通过DAVID数据库对共有靶点进行GO功能及KEGG通路富集分析;对核心成分与关键靶点进行分子对接验证。结果 共获得四逆散的活性成分136个,四逆散治疗溃疡性结肠炎和抑郁症的潜在作用靶点(共有靶点)220个,涉及657个生物过程、70个细胞组分、147个分子功能以及133条信号通路。筛选得到槲皮素、山柰酚、木犀草素、柚皮素、7-甲氧基-2-甲基异黄酮等核心活性化合物,JUN、MAPK3、STAT3、AKT1、MAPK1等关键靶蛋白,以及TNF、IL-17、Th17细胞分化、HIF-1、Toll样受体等信号通路。5个关键靶点均与槲皮素、山柰酚、木犀草素、柚皮素有较强的结合活性。结论 四逆散可能是通过槲皮素、山柰酚、木犀草素、柚皮素等活性成分,作用于JUN、MAPK3、STAT3、AKT1、MAPK1等关键靶点,通过TNF、IL-17、HIF-1、Toll样受体、Th17细胞分化等信号通路,发挥对溃疡性结肠炎与抑郁症“异病同治”的作用。