{"title":"结合肠道微生物数据和网络药理学探讨当归四逆汤对大鼠血瘀证的作用机制","authors":"Fengfeng Yu, Xiaoli Huang, Jiayu Liang, Shuyu Guan","doi":"10.37290/ctnr2641-452x.21:291-305","DOIUrl":null,"url":null,"abstract":"Danggui Sini decoction is a traditional Chinese medicine preparation commonly used in the treatment of blood stasis syndrome through a mechanism yet to be defined. Therefore, we have explored its mechanism of action by combining pharmacology and gut microbiota analysis. To this end, female Sprague-Dawley rats were divided into 5 groups, including the control group, the acute blood stasis group, the Danshen tablet-treated group, the low-dose Danggui Sini decoction group, and the high-dose Danggui Sini decoction group. Danggui Sini decoction led to a significant reduction in the changes in the whole blood viscosity and plasma viscosity of rats with acute blood stasis syndrome, improved the coagulation function and cardiopulmonary pathological injury, upregulated the plasma 6-keto prostaglandin F1α and endothelial nitric oxide synthase, and downregulated thromboxane B2 and endothelin-1. The high throughput 16S rRNA gene sequencing results showed that Danggui Sini decoction reduced the number of pathogenic proteobacteria, significantly reduced erysipelas and suzericella, and increased the beneficial bacteria Roche, effectively improving the status of intestinal flora disorder in acute blood stasis rats. The Spearman correlation analyses showed that there was a close correlation between intestinal flora distribution and changes in blood stasis-related biochemical indices. In addition, network pharmacological analysis showed that the epidermal growth factor receptor, tumor protein p53, signal transducer and activator of transcription 3, vascular endothelial growth factor A, and hypoxia-inducible factor 1-alpha were the core targets of Danggui Sini decoction in alleviation of blood stasis. Further genetic ontological and pathway enrichment analyses suggested that the therapeutic effect of Danggui Sini decoction on blood stasis involved the lipid and atherosclerosis pathways, advanced glycation end-product-receptor for advanced glycation end-product signaling pathways in diabetic complications, fluid shear stress and atherosclerosis pathways, and hypoxia-inducible factors, 1-alpha signaling pathway, phosphatidylinositol 3-kinase- protein kinase B signaling, and other pathways. These results are helpful in understanding the mechanism by which Danggui Sini decoction improves blood stasis and provide a reference for further research.","PeriodicalId":10976,"journal":{"name":"Current Topics in Nutraceutical Research","volume":null,"pages":null},"PeriodicalIF":0.4000,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Combining Gut Microbiota Data with Network Pharmacology to Explore the Mechanism of Danggui Sini Decoction Action Against Blood Stasis Syndrome in Rats\",\"authors\":\"Fengfeng Yu, Xiaoli Huang, Jiayu Liang, Shuyu Guan\",\"doi\":\"10.37290/ctnr2641-452x.21:291-305\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Danggui Sini decoction is a traditional Chinese medicine preparation commonly used in the treatment of blood stasis syndrome through a mechanism yet to be defined. Therefore, we have explored its mechanism of action by combining pharmacology and gut microbiota analysis. To this end, female Sprague-Dawley rats were divided into 5 groups, including the control group, the acute blood stasis group, the Danshen tablet-treated group, the low-dose Danggui Sini decoction group, and the high-dose Danggui Sini decoction group. Danggui Sini decoction led to a significant reduction in the changes in the whole blood viscosity and plasma viscosity of rats with acute blood stasis syndrome, improved the coagulation function and cardiopulmonary pathological injury, upregulated the plasma 6-keto prostaglandin F1α and endothelial nitric oxide synthase, and downregulated thromboxane B2 and endothelin-1. The high throughput 16S rRNA gene sequencing results showed that Danggui Sini decoction reduced the number of pathogenic proteobacteria, significantly reduced erysipelas and suzericella, and increased the beneficial bacteria Roche, effectively improving the status of intestinal flora disorder in acute blood stasis rats. The Spearman correlation analyses showed that there was a close correlation between intestinal flora distribution and changes in blood stasis-related biochemical indices. In addition, network pharmacological analysis showed that the epidermal growth factor receptor, tumor protein p53, signal transducer and activator of transcription 3, vascular endothelial growth factor A, and hypoxia-inducible factor 1-alpha were the core targets of Danggui Sini decoction in alleviation of blood stasis. Further genetic ontological and pathway enrichment analyses suggested that the therapeutic effect of Danggui Sini decoction on blood stasis involved the lipid and atherosclerosis pathways, advanced glycation end-product-receptor for advanced glycation end-product signaling pathways in diabetic complications, fluid shear stress and atherosclerosis pathways, and hypoxia-inducible factors, 1-alpha signaling pathway, phosphatidylinositol 3-kinase- protein kinase B signaling, and other pathways. These results are helpful in understanding the mechanism by which Danggui Sini decoction improves blood stasis and provide a reference for further research.\",\"PeriodicalId\":10976,\"journal\":{\"name\":\"Current Topics in Nutraceutical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.4000,\"publicationDate\":\"2023-07-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Topics in Nutraceutical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.37290/ctnr2641-452x.21:291-305\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"NUTRITION & DIETETICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Topics in Nutraceutical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.37290/ctnr2641-452x.21:291-305","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
Combining Gut Microbiota Data with Network Pharmacology to Explore the Mechanism of Danggui Sini Decoction Action Against Blood Stasis Syndrome in Rats
Danggui Sini decoction is a traditional Chinese medicine preparation commonly used in the treatment of blood stasis syndrome through a mechanism yet to be defined. Therefore, we have explored its mechanism of action by combining pharmacology and gut microbiota analysis. To this end, female Sprague-Dawley rats were divided into 5 groups, including the control group, the acute blood stasis group, the Danshen tablet-treated group, the low-dose Danggui Sini decoction group, and the high-dose Danggui Sini decoction group. Danggui Sini decoction led to a significant reduction in the changes in the whole blood viscosity and plasma viscosity of rats with acute blood stasis syndrome, improved the coagulation function and cardiopulmonary pathological injury, upregulated the plasma 6-keto prostaglandin F1α and endothelial nitric oxide synthase, and downregulated thromboxane B2 and endothelin-1. The high throughput 16S rRNA gene sequencing results showed that Danggui Sini decoction reduced the number of pathogenic proteobacteria, significantly reduced erysipelas and suzericella, and increased the beneficial bacteria Roche, effectively improving the status of intestinal flora disorder in acute blood stasis rats. The Spearman correlation analyses showed that there was a close correlation between intestinal flora distribution and changes in blood stasis-related biochemical indices. In addition, network pharmacological analysis showed that the epidermal growth factor receptor, tumor protein p53, signal transducer and activator of transcription 3, vascular endothelial growth factor A, and hypoxia-inducible factor 1-alpha were the core targets of Danggui Sini decoction in alleviation of blood stasis. Further genetic ontological and pathway enrichment analyses suggested that the therapeutic effect of Danggui Sini decoction on blood stasis involved the lipid and atherosclerosis pathways, advanced glycation end-product-receptor for advanced glycation end-product signaling pathways in diabetic complications, fluid shear stress and atherosclerosis pathways, and hypoxia-inducible factors, 1-alpha signaling pathway, phosphatidylinositol 3-kinase- protein kinase B signaling, and other pathways. These results are helpful in understanding the mechanism by which Danggui Sini decoction improves blood stasis and provide a reference for further research.
期刊介绍:
Current Topics in Nutraceutical Research is an international, interdisciplinary broad-based peer reviewed scientific journal for critical evaluation of research on chemistry, biology and therapeutic applications of nutraceuticals and functional foods. The major goal of this journal is to provide peer reviewed unbiased scientific data to the decision makers in the nutraceutical and food industry to help make informed choices about development of new products.
To this end, the journal will publish two types of review articles. First, a review of preclinical research data coming largely from animal, cell culture and other experimental models. Such data will provide basis for future product development and/or human research initiatives. Second, a critical evaluation of current human experimental data to help market and deliver the product for medically proven use. This journal will also serve as a forum for nutritionists, internists, neurologists, psychiatrists, and all those interested in preventive medicine.
The common denominator of all of the topic to be covered by the journal must include nutraceuticals and/functional food. The following is an example of some specific areas that may be of interest to the journal. i) Role of vitamins, minerals, antioxidants and phytonutrients on cardiovascular health, cancer, diabetes, ocular health, mental health, men’s health, women’s health, infant nutrition, ii) Role of herbals on human health, iii) Dietary supplements and sleep, iv) Components of diet that may have beneficial effect on human health, v) regulation of apoptosis and cell viability, vi) Isolation and characterization of bioactive components from functional foods, vii) Nutritional genomics, and viii) Nutritional proteomics.