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Chenglin Wang,1 Shilin Li,1 Yuzhou Shen,1 Yang Li,1 Muhu Chen,1 Youqiang Wang,2 Youyu Lan,3 Yingchun Hu1 1Department of Emergency Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Peopleâs Republic of China; 2Department of Laboratory Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Peopleâs Republic of China; 3Department of Rheumatology and Immunology, The Affiliated Hospital of Southwest Medical University, Luzhou, Peopleâs Republic of ChinaCorrespondence: Yingchun Hu, Department of Emergency Medicine, The Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Jiangyang District, Luzhou, Sichuan, Peopleâs Republic of China, Tel +86-15228232720, Fax +86-0830-3165120, Email huyingchun913@swmu.edu.cn Youyu Lan, Department of Rheumatology and Immunology, The Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Jiangyang District, Luzhou, Sichuan, Peopleâs Republic of China, Tel +86-18090861701, Fax +86-0830-3165120, Email 494077025@qq.comPurpose: To explore the potential active targets and mechanisms of Panax Ginseng in the treatment of sepsis using network pharmacology and RNA-seq technology.Patients and Methods: Patients with sepsis and healthy volunteers were collected according to SEPSIS 3.0, and their peripheral blood was used for RNA-seq analysis. The active ingredients and targets of Panax Ginseng were obtained using the TCMSP database, PPI and GO analysis were performed for disease-drug intersection targets. Then, we used Meta-analysis to screen core genes. Finally, single-cell RNA-seq was used to perform cell localization analysis on core genes.Results: RNA-seq analysis collected 4521 sepsis-related genes, TCMSP database obtained 86 Panax Ginseng active ingredients and their 294 active targets. PPI and GO analysis showed intersection targets were closely linked, and mainly involved in cellular response to chemical stress, response to drug and molecule of bacterial origin, etc. Then, core targets, IL1B, ALOX5, BCL2 and IL4R, were sorted by Meta-analysis, and all four genes have high expression in the sepsis survivor group compared to the sepsis non-survivor group; single-cell RNA-seq revealed that IL1B was mainly localized in macrophages, ALOX5 was mainly localized in macrophages and B cells, BCL2 was mainly localized in natural killer cells, T cells and B cells, IL4R was widely distributed in immune cells. Finally, according to the correspondence between the active ingredients and targets of Panax Ginseng in TCMSP database, we found that Ginsenoside rh2 regulates the expression of IL1B, Ginsenoside rf regulates the expression of IL1B and IL4R, Kaempferol regulates the expression of ALOX5 and BCL2, and β-sitosterol regulates the expression of BCL2.Conclusion: Ginsenoside rh2, Ginsenoside rf, Kaempferol and β-sitosterol may produce anti-sepsis effects by regulating the expression of IL1B, ALOX5, BCL2 and IL4R, thus improving the survival rate of sepsis patients.Keywords: Panax Ginseng, sepsis, RNA-seq, single-cell RNA-seq, network pharmacology |
