Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity...Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity of tissue cells undergoes extensive changes,which interfere with the normal function of immune cells.Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs,such as the stomach,liver,and colorectum.This metabolic-immune imbalance also corresponds to traditional Chinese medicine(TCM)theories of“yin-yang disharmony”and“disharmony between Ying-nutrients and Wei-defense.”The metabolic-immune imbalance has also been regarded as the key factor supporting“treatment of different diseases with the same method”,in which the same approach is adopted in the treatment of different conditions.In the TCM treatment process,it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function,thereby blocking the progression from inflammation to malignancy.Our study findings deepen the TCM understanding of metabolic-immune dysregulation and the relationship between metabolic-immune dysregulation,pattern identification,and treatment method.They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of“treating different diseases with the same method”.展开更多
Objective:Mendelian randomization(MR)has been widely utilized for causal inference between diseases,and its implementation within the domain of traditional Chinese medicine(TCM)is considered feasible.Although previous...Objective:Mendelian randomization(MR)has been widely utilized for causal inference between diseases,and its implementation within the domain of traditional Chinese medicine(TCM)is considered feasible.Although previous clinical and epidemiological studies have demonstrated a close relationship between insomnia and depression,the inherent genetic factors underlying these associations are unclear.The aim of this study was to evaluate the causal relationship between depression and insomnia via bidirectional 2-sample MR and increase the understanding of the TCM theory of treating different diseases with the same method,particularly in the context of comorbid depression and insomnia.Methods:Genetic data related to depression and insomnia were extracted from published genome-wide association studies(GWAS)data sets.Single-nucleotide polymorphisms(SNPs)associated with depression and insomnia were used as instrumental variables to construct an“SNP-exposure-outcome”model.Bidirectional 2-sample MR analysis was conducted via inverse-variance weighted(IVW),weighted median,MR Egger regression,simple mode,and weighted mode methods.Furthermore,heterogeneity tests,pleiotropy analyses,and sensitivity analyses were performed.Results:The MR results revealed a causal relationship between depression and an increased risk of developing insomnia(IVW,OR=1.400,95%CI:1.246–1.573,P<0.001),and a causal relationship between insomnia and an increased risk of developing depression(IVW,OR=1.204,95%CI:1.144–1.266,P<0.001).Conclusions:There is a bidirectional causal relationship between depression and insomnia.These findings provide new theoretical support for the TCM approach of treating different diseases with the same method in the prevention and treatment of depression and insomnia and provide a scientific basis for the modernization of TCM.展开更多
This paper introduced three cases of treating diseases with Tiaozhong Yiqi Decoction.Tiaozhong Yiqi Decoction,first proposed in Treatise on the Spleen and Stomach written by Li Gao,is an effective prescription for tre...This paper introduced three cases of treating diseases with Tiaozhong Yiqi Decoction.Tiaozhong Yiqi Decoction,first proposed in Treatise on the Spleen and Stomach written by Li Gao,is an effective prescription for treating the syndrome of dampness stagnancy due to spleen deficiency.The authors sorted out the treatment of some difficult and complicated diseases with this prescription and the curative effect is remarkable.Tiaozhong Yiqi Decoction is evolved from Buzhong Yiqi Decoction by removing ATRACTYLODIS MACROCEPHALAE RHIZOMA and ANGELICAE SINENSIS RADIX,and adding ATRACTYLODIS RHIZOMA and AUCKLANDIAE RADIX.It uses ASTRAGALI RADIX,GINSENG RADIX ET RHIZOMA,and GLYCYRRHIZAE RADIX ET RHIZOMA to benefit qi and invigorate spleen,so as to treat the deficiency of spleen;it uses BUPLEURI RADIX and CIMICIFUGAE RHIZOMA to raise the clear yang;it also uses ATRACTYLODIS RHIZOMA,CITRI RETICULATAE PERICARPIUM,and AUCKLANDIAE RADIX to harmonize the middle to dispel the dampness.In this paper,the case of tinnitus and deafness belongs to the syndrome of dampness stagnancy due to spleen deficiency,dampness obstruction due to qi block,and dampness accumulation affecting clear orifices.The case of red vaginal discharge belongs to the syndrome of sunken spleen qi due to spleen deficiency and sunken yin fire.The case of cough belongs to the spleen deficiency combined with earth not engendering metal.All cases were treated with Tiaozhong Yiqi Decoction,fully proving the mechanism of the same treatment for different diseases.Only by identifying disease causes and syndromes,may it be able to obtain remarkable curative effect.展开更多
Objective： To identify the commonalities between rheumatoid arthritis （RA） and diabetes mellitus （DM） to understand the mechanisms of Chinese medicine （CM） in different diseases with the same treatment. Methods...Objective： To identify the commonalities between rheumatoid arthritis （RA） and diabetes mellitus （DM） to understand the mechanisms of Chinese medicine （CM） in different diseases with the same treatment. Methods： A text mining approach was adopted to analyze the commonalities between RA and DM according to CM and biological elements. The major commonalities were subsequently verified in RA and DM rat models, in which herbal formula for the treatment of both RA and DM identified via text mining was used as the intervention. Results： Similarities were identified between RA and DM regarding the CM approach used for diagnosis and treatment, as well as the networks of biological activities affected by each disease, including the involvement of adhesion molecules, oxidative stress, cytokines, T-lymphocytes, apoptosis, and inflammation. The Ramulus Cinnamomi-Radix Paeoniae Alba-Rhizoma Anemarrhenae is an herbal combination used to treat RA and DM. This formula demonstrated similar effects on oxidative stress and inflammation in rats with collagen-induced arthritis, which supports the text mining results regarding the commonalities between RA and DM. Conclusion： Commonalities between the biological activities involved in RA and DM were identified through text mining, and both RA and DM might be responsive to the same intervention at a specific stage.展开更多
Objective To predict the molecular mechanism of Dihuang(Rehmanniae Radix)in the treatment of diabetic nephropathy(DN)complicated with depression based on network pharmacology.Methods The components of Dihuang(Rehmanni...Objective To predict the molecular mechanism of Dihuang(Rehmanniae Radix)in the treatment of diabetic nephropathy(DN)complicated with depression based on network pharmacology.Methods The components of Dihuang(Rehmanniae Radix)were identified from the Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP),Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and relevant literature.The component targets were detected by combining the SwissTargetPrediction and Pub Chem databases.Disease targets were collected from the Therapeutic Target Database(TTD),Dis Ge NET,and Ensembl databases with“diabetic nephropathy”and“depression”as keywords.The disease-component targets were mapped using Venny 2.1.0 to obtain potential targets.A protein-protein interaction(PPI)network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database and Cytoscape 3.7.2.The co-expression genes of the key targets were collected based on the COXPRESdb 7.3.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed for potential targets using R language.Target-component docking was verified and evaluated using Discovery Studio 4.5.Results According to the databases and literature reports,Dihuang(Rehmanniae Radix)contained 65 active components,and had 155 related targets for the treatment of DN complicated with depression.PPI screening showed that the key targets included serine/threonine protein kinase 1(AKT1),signal transducer and activator transcription 3(STAT3),interleukin 6(IL-6),mitogen-activated protein kinase 1(MAPK1),and vascular endothelial growth factor A(VEGFA),etc.GO enrichment analysis mainly involved biological processes,such as lipid metabolism,protein secretion regulation,cell homeostasis,and phosphatidylinositol 3 kinase activity.KEGG pathway enrichment analysis included the role of the AGE-RAGE signaling pathway in diabetic complements,insulin resistance(IR),neurotrophin signal path,Toll-like receptor signaling pathway,relaxin signaling pathway,epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs),etc.Molecular docking showed that the target had high affinity for stachyose,manninotriose,verbascose,nigerose,etc.Conclusion Based on network parmacology,this study preliminarily predict the effects of Dihuang(Rehmanniae Radix)in treating DN complicated with depression by regulating inflammation,glucose metabolism,nution nerve,etc.展开更多
Objective: "Same treatment for different diseases" is a unique treatment strategy under the guidance of traditional Chinese medicine(TCM) theory.Codonopsis Radix(Codonopsis pilosula,Dangshen in Chinese)with ...Objective: "Same treatment for different diseases" is a unique treatment strategy under the guidance of traditional Chinese medicine(TCM) theory.Codonopsis Radix(Codonopsis pilosula,Dangshen in Chinese)with spleen-fortifying effect was employed to understand the strategy of "Same treatment for different diseases",based on its common mechanism in the treatment of gastric diseases including gastric ulcer,gastritis and gastric cancer via network pharmacology research.Methods:Network pharmacology research methods were used to analyze the interaction network and potential mechanisms of Dangshen in treating gastric ulcer,gastritis and gastric cancer.The active components and their target proteins of Dangshen were integrated from TCMSP,BATMAN-TCM databases.The targets of gastric ulcer,gastritis and gastric cancer were collected through GeneCards,PubMed,TDD and DisGeNET Database.Through screening,the key components and the key targets of Dangshen in treating gastric ulcer,gastritis and gastric cancer were obtained.After KEGG pathway analysis and GO analysis,the important pathways and biological processes were analyzed.Results:Through data and literature mining,the common and specific pharmaceutical effects and mechanism of Dangshen were summarized in these three gastric lesions.It was shown that Dangshen mainly acted on gastric ulcer,gastritis and gastric cancer through the overall regulation of the PI3K-AkT signaling pathway.With the development of the disease,it will gradually increase the control of inflammation through TNF,NF-κB and other inflammation-related signaling pathways to reduce inflammatory damage.For tumorigenesis,it pays more attention to inhibiting the ErbB signaling pathways to reduce the proliferation and migration of tumor cells.In addition,Dangshen's regulation of HIF-1 signaling pathway may also be beneficial for the treatment of gastric ulcer,gastritis and gastric cancer.Conclusion:Dangshen achieves spleen-fortifying effect on gastric diseases including gastric ulcer,gastritis and gastric cancer through multiple targets in multiple pathways,especially PI3K-AKT pathway and HIF-1 pathway.It could provide a scientific basis for understanding the strategy of "Same treatment for different diseases" in traditional Chinese medicine.展开更多
目的:应用网络药理学方法探讨三仁汤治疗多囊卵巢综合征(polycystic ovary syndrome,PCOS)和2型糖尿病(type 2 diabetes mellitus,T2DM)的作用机制,为中药“异病同治”提供科学的理论依据。方法:利用中药数据库(traditional Chinese med...目的:应用网络药理学方法探讨三仁汤治疗多囊卵巢综合征(polycystic ovary syndrome,PCOS)和2型糖尿病(type 2 diabetes mellitus,T2DM)的作用机制,为中药“异病同治”提供科学的理论依据。方法:利用中药数据库(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、中医药综合数据库(traditional Chinese medicine integrated database,TCMID)、中医药整合药理学研究平台(integrative pharmacology-based research platform of traditional Chinese medicine,TCMIP)、中药成分靶点平台2.0(HIT 2.0)、传统中医分子机制生物信息学分析工具(bioinformatics analysis tool for molecular mechANism of traditional Chinese medicine,BATMAN-TCM)、草药-中医证候-西医症状-成分-靶标-疾病关联网络数据库(symmap integrates traditional Chinese medicine,SymMap)等平台获取和筛选三仁汤的活性成分,并判断其生物活性;得到有效活性成分对应的靶点基因,输入Uniprot数据库,将靶点标准化;利用人类基因组数据库(the Human Gene database,GeneCards)、药物靶标数据库(therapeutic target database,TTD)、比较毒物基因组学数据库(the comparative toxicogenomics database,CTD)和药物银行数据库(DrugBank)获取PCOS和T2DM疾病靶点,得到三仁汤治疗PCOS和T2DM的共同作用靶点;采用Cytoscape 3.7.1软件绘制三仁汤“异病同治”的“单味药-活性成分-共同靶点”网络图;利用STRING平台绘制蛋白相互作用网络;通过注释、可视化和综合发现数据库(the database for annotation,visualization and integrated discovery,DAVID)、R语言(R studio)等平台进行生物过程分析,获得Mode节点分析、基因本体论(gene ontology,GO)富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析结果。结果:共筛选得到三仁汤有效活性成分50个、PCOS疾病靶点23332个、T2DM疾病靶点28438个,三仁汤“异病同治”PCOS和T2DM的共同靶点214个;蛋白质相互作用(protein-protein interaction networks,PPI)筛选出39个关键靶点;GO及KEGG富集分析结果显示:三仁汤“异病同治”主要涉及炎症反应、缺氧反应、凋亡过程、HIF-1信号通路、钙离子信号通路、胰岛素抵抗等;MCODE分析结果显示:三仁汤“异病同治”可能与活性氧反应、凋亡相关信号通路、白细胞介素17(interleukin-17,IL-17)信号通路、脂肪酸代谢过程等相关;三仁汤“异病同治”的关键靶点为蛋白激酶B1(protein kinase b alpha,AKT1)、肿瘤蛋白53(tumor protein p53,TP53)、半胱天冬酶3(caspase 3,CASP3)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)及IL-6等。结论:三仁汤可能通过多靶点、多通路、多途径的作用机制,对PCOS和T2DM患者发挥作用,取得异病同治的效果。展开更多
目的:基于网络药理学联合分析对接法探究八珍汤治疗股骨头坏死(osteonecrosis of the femoral head,ONFH)及骨肉瘤(osteosarcoma,OS)的潜在机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharma...目的:基于网络药理学联合分析对接法探究八珍汤治疗股骨头坏死(osteonecrosis of the femoral head,ONFH)及骨肉瘤(osteosarcoma,OS)的潜在机制。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 plsatform,TCMSP)下载活性成分和相关靶点,通过人类基因数据库(the human gene database,GeneCards)、在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)下载ONFH、OS相关疾病靶点。使用R软件取交集后,再与两病共有基因取交集。利用STRING数据库对交集靶点构建蛋白互作网络图,利用R软件进行基因本体(gene ontology,GO)与京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析,运行Autodock Vina对活性成分及关键蛋白进行对接。结果:筛选获得八珍汤疾病相关有效成分共159个,相关靶点1965个,ONFH、OS共有靶点615个,药物与两种疾病交集获得药物疾病靶点124个。GO富集分析获得BP相关条目2082个,CC相关条目42个,MF相关条目122个。KEGG功能富集分析发现糖尿病并发症中的高级糖基化终末产物-受体(advanced glycation end products-receptor,AGE-RAGE)、脂质与动脉粥样硬化(lipid and atherosclerosis)、乙型肝炎(hepatitis B)、前列腺癌(prostate cancer)、胰腺癌(pancreatic cancer)等161条信号通路,分子对接初步验证了八珍汤主要活性成分能与关键靶点发生相互作用。结论:Akt1作为关键基因,通过调节局部血管微循环、骨代谢达到治疗ONFH、OS的目的,为后续研究八珍汤治疗ONFH、OS的临床应用具有指导意义,并从现代医学的角度诠释中医中药异病同治的原理。展开更多
基金supported by National Natural Science Foundation of China(92059102 and 81630080)the National Key Research and Development Plan of China(2018YFC1704106).
文摘Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity of tissue cells undergoes extensive changes,which interfere with the normal function of immune cells.Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs,such as the stomach,liver,and colorectum.This metabolic-immune imbalance also corresponds to traditional Chinese medicine(TCM)theories of“yin-yang disharmony”and“disharmony between Ying-nutrients and Wei-defense.”The metabolic-immune imbalance has also been regarded as the key factor supporting“treatment of different diseases with the same method”,in which the same approach is adopted in the treatment of different conditions.In the TCM treatment process,it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function,thereby blocking the progression from inflammation to malignancy.Our study findings deepen the TCM understanding of metabolic-immune dysregulation and the relationship between metabolic-immune dysregulation,pattern identification,and treatment method.They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of“treating different diseases with the same method”.
基金supported by the China Academy of ChineseMedical Science(CACMS)Innovation Fund(No.CI2021A00603)the National Natural Science Foundation of China(No.82074299).
文摘Objective:Mendelian randomization(MR)has been widely utilized for causal inference between diseases,and its implementation within the domain of traditional Chinese medicine(TCM)is considered feasible.Although previous clinical and epidemiological studies have demonstrated a close relationship between insomnia and depression,the inherent genetic factors underlying these associations are unclear.The aim of this study was to evaluate the causal relationship between depression and insomnia via bidirectional 2-sample MR and increase the understanding of the TCM theory of treating different diseases with the same method,particularly in the context of comorbid depression and insomnia.Methods:Genetic data related to depression and insomnia were extracted from published genome-wide association studies(GWAS)data sets.Single-nucleotide polymorphisms(SNPs)associated with depression and insomnia were used as instrumental variables to construct an“SNP-exposure-outcome”model.Bidirectional 2-sample MR analysis was conducted via inverse-variance weighted(IVW),weighted median,MR Egger regression,simple mode,and weighted mode methods.Furthermore,heterogeneity tests,pleiotropy analyses,and sensitivity analyses were performed.Results:The MR results revealed a causal relationship between depression and an increased risk of developing insomnia(IVW,OR=1.400,95%CI:1.246–1.573,P<0.001),and a causal relationship between insomnia and an increased risk of developing depression(IVW,OR=1.204,95%CI:1.144–1.266,P<0.001).Conclusions:There is a bidirectional causal relationship between depression and insomnia.These findings provide new theoretical support for the TCM approach of treating different diseases with the same method in the prevention and treatment of depression and insomnia and provide a scientific basis for the modernization of TCM.
基金Supported by Project of National Natural Science Foundation of China(GJJ15021)Project of Guangxi Graduate Education Innovation Program(YCSY2018025)
文摘This paper introduced three cases of treating diseases with Tiaozhong Yiqi Decoction.Tiaozhong Yiqi Decoction,first proposed in Treatise on the Spleen and Stomach written by Li Gao,is an effective prescription for treating the syndrome of dampness stagnancy due to spleen deficiency.The authors sorted out the treatment of some difficult and complicated diseases with this prescription and the curative effect is remarkable.Tiaozhong Yiqi Decoction is evolved from Buzhong Yiqi Decoction by removing ATRACTYLODIS MACROCEPHALAE RHIZOMA and ANGELICAE SINENSIS RADIX,and adding ATRACTYLODIS RHIZOMA and AUCKLANDIAE RADIX.It uses ASTRAGALI RADIX,GINSENG RADIX ET RHIZOMA,and GLYCYRRHIZAE RADIX ET RHIZOMA to benefit qi and invigorate spleen,so as to treat the deficiency of spleen;it uses BUPLEURI RADIX and CIMICIFUGAE RHIZOMA to raise the clear yang;it also uses ATRACTYLODIS RHIZOMA,CITRI RETICULATAE PERICARPIUM,and AUCKLANDIAE RADIX to harmonize the middle to dispel the dampness.In this paper,the case of tinnitus and deafness belongs to the syndrome of dampness stagnancy due to spleen deficiency,dampness obstruction due to qi block,and dampness accumulation affecting clear orifices.The case of red vaginal discharge belongs to the syndrome of sunken spleen qi due to spleen deficiency and sunken yin fire.The case of cough belongs to the spleen deficiency combined with earth not engendering metal.All cases were treated with Tiaozhong Yiqi Decoction,fully proving the mechanism of the same treatment for different diseases.Only by identifying disease causes and syndromes,may it be able to obtain remarkable curative effect.
基金Supported by the National Natural Science Foundation of China(No.81573845,81473367,81403209,30825047)China Academy of Chinese Medical Sciences Project(No.Z0412)Beijing Nova Program(No.xx2014B073)
文摘Objective： To identify the commonalities between rheumatoid arthritis （RA） and diabetes mellitus （DM） to understand the mechanisms of Chinese medicine （CM） in different diseases with the same treatment. Methods： A text mining approach was adopted to analyze the commonalities between RA and DM according to CM and biological elements. The major commonalities were subsequently verified in RA and DM rat models, in which herbal formula for the treatment of both RA and DM identified via text mining was used as the intervention. Results： Similarities were identified between RA and DM regarding the CM approach used for diagnosis and treatment, as well as the networks of biological activities affected by each disease, including the involvement of adhesion molecules, oxidative stress, cytokines, T-lymphocytes, apoptosis, and inflammation. The Ramulus Cinnamomi-Radix Paeoniae Alba-Rhizoma Anemarrhenae is an herbal combination used to treat RA and DM. This formula demonstrated similar effects on oxidative stress and inflammation in rats with collagen-induced arthritis, which supports the text mining results regarding the commonalities between RA and DM. Conclusion： Commonalities between the biological activities involved in RA and DM were identified through text mining, and both RA and DM might be responsive to the same intervention at a specific stage.
基金National Natural Science Foundation of China(81960714)Jiangxi University of Chinese Medicine Graduate Innovation Project(JZYC21S52)。
文摘Objective To predict the molecular mechanism of Dihuang(Rehmanniae Radix)in the treatment of diabetic nephropathy(DN)complicated with depression based on network pharmacology.Methods The components of Dihuang(Rehmanniae Radix)were identified from the Integrated Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP),Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and relevant literature.The component targets were detected by combining the SwissTargetPrediction and Pub Chem databases.Disease targets were collected from the Therapeutic Target Database(TTD),Dis Ge NET,and Ensembl databases with“diabetic nephropathy”and“depression”as keywords.The disease-component targets were mapped using Venny 2.1.0 to obtain potential targets.A protein-protein interaction(PPI)network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database and Cytoscape 3.7.2.The co-expression genes of the key targets were collected based on the COXPRESdb 7.3.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed for potential targets using R language.Target-component docking was verified and evaluated using Discovery Studio 4.5.Results According to the databases and literature reports,Dihuang(Rehmanniae Radix)contained 65 active components,and had 155 related targets for the treatment of DN complicated with depression.PPI screening showed that the key targets included serine/threonine protein kinase 1(AKT1),signal transducer and activator transcription 3(STAT3),interleukin 6(IL-6),mitogen-activated protein kinase 1(MAPK1),and vascular endothelial growth factor A(VEGFA),etc.GO enrichment analysis mainly involved biological processes,such as lipid metabolism,protein secretion regulation,cell homeostasis,and phosphatidylinositol 3 kinase activity.KEGG pathway enrichment analysis included the role of the AGE-RAGE signaling pathway in diabetic complements,insulin resistance(IR),neurotrophin signal path,Toll-like receptor signaling pathway,relaxin signaling pathway,epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs),etc.Molecular docking showed that the target had high affinity for stachyose,manninotriose,verbascose,nigerose,etc.Conclusion Based on network parmacology,this study preliminarily predict the effects of Dihuang(Rehmanniae Radix)in treating DN complicated with depression by regulating inflammation,glucose metabolism,nution nerve,etc.
基金financially supported by the National Key Research and Development Program of China (2018YFC1706300 and 2018YFC17063005)the Fundamental Research Funds for the Central Universities (lzujbky-2019-92, lzujbky-2020-sp13)+2 种基金the Project for Longyuan Youth Innovation and Entrepreneurship TalentScience the Special funds for Innovation and Guidance of Gansu (2017ZX-02)the Science-Technology Plan Project from Lanzhou Science and Technology Bureau (2017-RC115)。
文摘Objective: "Same treatment for different diseases" is a unique treatment strategy under the guidance of traditional Chinese medicine(TCM) theory.Codonopsis Radix(Codonopsis pilosula,Dangshen in Chinese)with spleen-fortifying effect was employed to understand the strategy of "Same treatment for different diseases",based on its common mechanism in the treatment of gastric diseases including gastric ulcer,gastritis and gastric cancer via network pharmacology research.Methods:Network pharmacology research methods were used to analyze the interaction network and potential mechanisms of Dangshen in treating gastric ulcer,gastritis and gastric cancer.The active components and their target proteins of Dangshen were integrated from TCMSP,BATMAN-TCM databases.The targets of gastric ulcer,gastritis and gastric cancer were collected through GeneCards,PubMed,TDD and DisGeNET Database.Through screening,the key components and the key targets of Dangshen in treating gastric ulcer,gastritis and gastric cancer were obtained.After KEGG pathway analysis and GO analysis,the important pathways and biological processes were analyzed.Results:Through data and literature mining,the common and specific pharmaceutical effects and mechanism of Dangshen were summarized in these three gastric lesions.It was shown that Dangshen mainly acted on gastric ulcer,gastritis and gastric cancer through the overall regulation of the PI3K-AkT signaling pathway.With the development of the disease,it will gradually increase the control of inflammation through TNF,NF-κB and other inflammation-related signaling pathways to reduce inflammatory damage.For tumorigenesis,it pays more attention to inhibiting the ErbB signaling pathways to reduce the proliferation and migration of tumor cells.In addition,Dangshen's regulation of HIF-1 signaling pathway may also be beneficial for the treatment of gastric ulcer,gastritis and gastric cancer.Conclusion:Dangshen achieves spleen-fortifying effect on gastric diseases including gastric ulcer,gastritis and gastric cancer through multiple targets in multiple pathways,especially PI3K-AKT pathway and HIF-1 pathway.It could provide a scientific basis for understanding the strategy of "Same treatment for different diseases" in traditional Chinese medicine.
文摘目的:应用网络药理学方法探讨三仁汤治疗多囊卵巢综合征(polycystic ovary syndrome,PCOS)和2型糖尿病(type 2 diabetes mellitus,T2DM)的作用机制,为中药“异病同治”提供科学的理论依据。方法:利用中药数据库(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、中医药综合数据库(traditional Chinese medicine integrated database,TCMID)、中医药整合药理学研究平台(integrative pharmacology-based research platform of traditional Chinese medicine,TCMIP)、中药成分靶点平台2.0(HIT 2.0)、传统中医分子机制生物信息学分析工具(bioinformatics analysis tool for molecular mechANism of traditional Chinese medicine,BATMAN-TCM)、草药-中医证候-西医症状-成分-靶标-疾病关联网络数据库(symmap integrates traditional Chinese medicine,SymMap)等平台获取和筛选三仁汤的活性成分,并判断其生物活性;得到有效活性成分对应的靶点基因,输入Uniprot数据库,将靶点标准化;利用人类基因组数据库(the Human Gene database,GeneCards)、药物靶标数据库(therapeutic target database,TTD)、比较毒物基因组学数据库(the comparative toxicogenomics database,CTD)和药物银行数据库(DrugBank)获取PCOS和T2DM疾病靶点,得到三仁汤治疗PCOS和T2DM的共同作用靶点;采用Cytoscape 3.7.1软件绘制三仁汤“异病同治”的“单味药-活性成分-共同靶点”网络图;利用STRING平台绘制蛋白相互作用网络;通过注释、可视化和综合发现数据库(the database for annotation,visualization and integrated discovery,DAVID)、R语言(R studio)等平台进行生物过程分析,获得Mode节点分析、基因本体论(gene ontology,GO)富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析结果。结果:共筛选得到三仁汤有效活性成分50个、PCOS疾病靶点23332个、T2DM疾病靶点28438个,三仁汤“异病同治”PCOS和T2DM的共同靶点214个;蛋白质相互作用(protein-protein interaction networks,PPI)筛选出39个关键靶点;GO及KEGG富集分析结果显示:三仁汤“异病同治”主要涉及炎症反应、缺氧反应、凋亡过程、HIF-1信号通路、钙离子信号通路、胰岛素抵抗等;MCODE分析结果显示:三仁汤“异病同治”可能与活性氧反应、凋亡相关信号通路、白细胞介素17(interleukin-17,IL-17)信号通路、脂肪酸代谢过程等相关;三仁汤“异病同治”的关键靶点为蛋白激酶B1(protein kinase b alpha,AKT1)、肿瘤蛋白53(tumor protein p53,TP53)、半胱天冬酶3(caspase 3,CASP3)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)及IL-6等。结论:三仁汤可能通过多靶点、多通路、多途径的作用机制,对PCOS和T2DM患者发挥作用,取得异病同治的效果。
文摘目的:基于网络药理学联合分析对接法探究八珍汤治疗股骨头坏死(osteonecrosis of the femoral head,ONFH)及骨肉瘤(osteosarcoma,OS)的潜在机制。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 plsatform,TCMSP)下载活性成分和相关靶点,通过人类基因数据库(the human gene database,GeneCards)、在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)下载ONFH、OS相关疾病靶点。使用R软件取交集后,再与两病共有基因取交集。利用STRING数据库对交集靶点构建蛋白互作网络图,利用R软件进行基因本体(gene ontology,GO)与京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析,运行Autodock Vina对活性成分及关键蛋白进行对接。结果:筛选获得八珍汤疾病相关有效成分共159个,相关靶点1965个,ONFH、OS共有靶点615个,药物与两种疾病交集获得药物疾病靶点124个。GO富集分析获得BP相关条目2082个,CC相关条目42个,MF相关条目122个。KEGG功能富集分析发现糖尿病并发症中的高级糖基化终末产物-受体(advanced glycation end products-receptor,AGE-RAGE)、脂质与动脉粥样硬化(lipid and atherosclerosis)、乙型肝炎(hepatitis B)、前列腺癌(prostate cancer)、胰腺癌(pancreatic cancer)等161条信号通路,分子对接初步验证了八珍汤主要活性成分能与关键靶点发生相互作用。结论:Akt1作为关键基因,通过调节局部血管微循环、骨代谢达到治疗ONFH、OS的目的,为后续研究八珍汤治疗ONFH、OS的临床应用具有指导意义,并从现代医学的角度诠释中医中药异病同治的原理。
