Hydroxysafflor Yellow A modulation of metabolite networks and inhibition of JAK2/STAT1 pathway in sepsis
Abstract Sepsis, a severe infectious disease causing multiple organ dysfunction, requires further exploration of its pathomechanisms and therapeutic options. Hydroxysafflor Yellow A (HYSA), extracted from Carthamus tinctorius L, has shown anti-inflammatory and antioxidant properties effective in tre...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-11545-2 |
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| author | Bingbing Pan Fengting Chen Siyan Shen Yu Jiang Ying Yang Jia Wang Yanjuan Liu Lai Wei Jitong Liu Gaoyin Kong Xuan He Bing Guo |
| author_facet | Bingbing Pan Fengting Chen Siyan Shen Yu Jiang Ying Yang Jia Wang Yanjuan Liu Lai Wei Jitong Liu Gaoyin Kong Xuan He Bing Guo |
| author_sort | Bingbing Pan |
| collection | DOAJ |
| description | Abstract Sepsis, a severe infectious disease causing multiple organ dysfunction, requires further exploration of its pathomechanisms and therapeutic options. Hydroxysafflor Yellow A (HYSA), extracted from Carthamus tinctorius L, has shown anti-inflammatory and antioxidant properties effective in treating sepsis, though its precise mechanism remains unclear. In this study, a cecum ligation puncture (CLP) model was used to evaluate HYSA’s effects on sepsis-induced organ injury. HYSA (300 mg/kg) was administered intraperitoneally 4 h post-CLP. Results showed that HYSA inhibited the inflammatory response and improved pathological scores in the liver, lungs, and kidneys. Metabolomics analysis identified key metabolites and pathways influenced by HYSA, including nicotinate and nicotinamide metabolism and glycine/serine metabolism. Network pharmacology and molecular docking identified JAK2/STAT1 as potential targets, with Western blotting confirmed that HYSA inhibits JAK2/STAT1 phosphorylation. These findings suggest that HYSA protects against sepsis-induced organ injury by regulating metabolic networks and modulating the JAK2/STAT1 pathway. |
| format | Article |
| id | doaj-art-e16627d45d5f4d0a938a1a9c38dcdfd5 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-e16627d45d5f4d0a938a1a9c38dcdfd52025-08-20T03:46:08ZengNature PortfolioScientific Reports2045-23222025-07-0115111810.1038/s41598-025-11545-2Hydroxysafflor Yellow A modulation of metabolite networks and inhibition of JAK2/STAT1 pathway in sepsisBingbing Pan0Fengting Chen1Siyan Shen2Yu Jiang3Ying Yang4Jia Wang5Yanjuan Liu6Lai Wei7Jitong Liu8Gaoyin Kong9Xuan He10Bing Guo11Department of Anesthesiology, Clinical Research Center for Anesthesiology of ERAS in Hunan Province, Hunan Provincial People’s Hospital and The First Affiliated Hospital of Hunan Normal UniversityThe First Affiliated Hospital of Hunan Normal University (Hunan Provincial People’s Hospital)The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People’s Hospital)Department of Emergency Medicine, Clinical Research Center For Emergency and Critical Care in Hunan Province, Hunan Provincial Key Laboratory of Emergency and Critical Care Metabonomics, Hunan Provincial Institute of Emergency Medicine, Hunan Provincial People’s Hospital and The First Affiliated Hospital of Hunan Normal UniversityDepartment of Anesthesiology, Clinical Research Center for Anesthesiology of ERAS in Hunan Province, Hunan Provincial People’s Hospital and The First Affiliated Hospital of Hunan Normal UniversityHunan Provincial Key Laboratory of Emergency and Critical Care Metabonomics, Hunan Provincial People’s Hospital and The First Affiliated Hospital of Hunan Normal UniversityDepartment of Emergency Medicine, Clinical Research Center For Emergency and Critical Care in Hunan Province, Hunan Provincial Key Laboratory of Emergency and Critical Care Metabonomics, Hunan Provincial Institute of Emergency Medicine, Hunan Provincial People’s Hospital and The First Affiliated Hospital of Hunan Normal UniversityDepartment of Anesthesiology, Clinical Research Center for Anesthesiology of ERAS in Hunan Province, Hunan Provincial People’s Hospital and The First Affiliated Hospital of Hunan Normal UniversityDepartment of Anesthesiology, Clinical Research Center for Anesthesiology of ERAS in Hunan Province, Hunan Provincial People’s Hospital and The First Affiliated Hospital of Hunan Normal UniversityDepartment of Anesthesiology, Clinical Research Center for Anesthesiology of ERAS in Hunan Province, Hunan Provincial People’s Hospital and The First Affiliated Hospital of Hunan Normal UniversityCollege of Traditional Chinese Medicine, Changsha Medical UniversityHunan University of Chinese MedicineAbstract Sepsis, a severe infectious disease causing multiple organ dysfunction, requires further exploration of its pathomechanisms and therapeutic options. Hydroxysafflor Yellow A (HYSA), extracted from Carthamus tinctorius L, has shown anti-inflammatory and antioxidant properties effective in treating sepsis, though its precise mechanism remains unclear. In this study, a cecum ligation puncture (CLP) model was used to evaluate HYSA’s effects on sepsis-induced organ injury. HYSA (300 mg/kg) was administered intraperitoneally 4 h post-CLP. Results showed that HYSA inhibited the inflammatory response and improved pathological scores in the liver, lungs, and kidneys. Metabolomics analysis identified key metabolites and pathways influenced by HYSA, including nicotinate and nicotinamide metabolism and glycine/serine metabolism. Network pharmacology and molecular docking identified JAK2/STAT1 as potential targets, with Western blotting confirmed that HYSA inhibits JAK2/STAT1 phosphorylation. These findings suggest that HYSA protects against sepsis-induced organ injury by regulating metabolic networks and modulating the JAK2/STAT1 pathway.https://doi.org/10.1038/s41598-025-11545-2Hydroxysafflor Yellow ASepsisMulti-organ damageMetabolomicsNetwork pharmacologyJAK2/STAT1 |
| spellingShingle | Bingbing Pan Fengting Chen Siyan Shen Yu Jiang Ying Yang Jia Wang Yanjuan Liu Lai Wei Jitong Liu Gaoyin Kong Xuan He Bing Guo Hydroxysafflor Yellow A modulation of metabolite networks and inhibition of JAK2/STAT1 pathway in sepsis Scientific Reports Hydroxysafflor Yellow A Sepsis Multi-organ damage Metabolomics Network pharmacology JAK2/STAT1 |
| title | Hydroxysafflor Yellow A modulation of metabolite networks and inhibition of JAK2/STAT1 pathway in sepsis |
| title_full | Hydroxysafflor Yellow A modulation of metabolite networks and inhibition of JAK2/STAT1 pathway in sepsis |
| title_fullStr | Hydroxysafflor Yellow A modulation of metabolite networks and inhibition of JAK2/STAT1 pathway in sepsis |
| title_full_unstemmed | Hydroxysafflor Yellow A modulation of metabolite networks and inhibition of JAK2/STAT1 pathway in sepsis |
| title_short | Hydroxysafflor Yellow A modulation of metabolite networks and inhibition of JAK2/STAT1 pathway in sepsis |
| title_sort | hydroxysafflor yellow a modulation of metabolite networks and inhibition of jak2 stat1 pathway in sepsis |
| topic | Hydroxysafflor Yellow A Sepsis Multi-organ damage Metabolomics Network pharmacology JAK2/STAT1 |
| url | https://doi.org/10.1038/s41598-025-11545-2 |
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