Parthenolide improves sepsis-induced coagulopathy by inhibiting mitochondrial-mediated apoptosis in vascular endothelial cells through BRD4/BCL-xL pathway
Abstract Background Sepsis is a systemic inflammatory syndrome that can cause coagulation abnormalities, leading to damage in multiple organs. Vascular endothelial cells (VECs) are crucial in the development of sepsis-induced coagulopathy (SIC). The role of Parthenolide (PTL) in regulating SIC by pr...
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2025-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06114-0 |
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| author | Jun Zhang Xing Zhu Yong Li Yinyu Wu Yunxia Du Hai Yang Zhengchao Liu Haoyu Pei Rui Li Huan Luo Deyu Zuo Han She Qingxiang Mao |
| author_facet | Jun Zhang Xing Zhu Yong Li Yinyu Wu Yunxia Du Hai Yang Zhengchao Liu Haoyu Pei Rui Li Huan Luo Deyu Zuo Han She Qingxiang Mao |
| author_sort | Jun Zhang |
| collection | DOAJ |
| description | Abstract Background Sepsis is a systemic inflammatory syndrome that can cause coagulation abnormalities, leading to damage in multiple organs. Vascular endothelial cells (VECs) are crucial in the development of sepsis-induced coagulopathy (SIC). The role of Parthenolide (PTL) in regulating SIC by protecting VECs remains unclear. Methods The study utilized septic rats and lipopolysaccharide (LPS)-stimulated VECs to simulate a SIC model and observe the therapeutic effects of PTL. Additionally, nanotechnology was employed to produce Nano-PTL (N-PTL), to observe whether it has advantages over PTL in treating SIC. Results PTL has been shown to mitigate lung injury in septic rats, significantly reduce tumor necrosis factor-α (TNF-α) levels, and increase survival rates. PTL treatment also enhances coagulation function, augments vascular endothelial cell (VEC) function, reduces mitochondrial fragmentation, and increases both mitochondrial oxygen consumption rate (OCR) and mitochondrial membrane potential (MMP), while inhibiting reactive oxygen species (ROS) production. By increasing BRD4/BCL-xL levels, PTL can prevent mitochondrial-mediated apoptosis in VECs, improve VEC function, and consequently ameliorate SIC. Additionally, nanotechnology-synthesized N-PTL further enhances the protective effects on VECs and coagulation function. Conclusions This study clarifies the therapeutic effects and mechanisms of PTL on SIC, offering new strategies and directions for the treatment of sepsis. |
| format | Article |
| id | doaj-art-4509fb4edb914c91a104590096bb5f43 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-4509fb4edb914c91a104590096bb5f432025-01-19T12:37:13ZengBMCJournal of Translational Medicine1479-58762025-01-0123111610.1186/s12967-025-06114-0Parthenolide improves sepsis-induced coagulopathy by inhibiting mitochondrial-mediated apoptosis in vascular endothelial cells through BRD4/BCL-xL pathwayJun Zhang0Xing Zhu1Yong Li2Yinyu Wu3Yunxia Du4Hai Yang5Zhengchao Liu6Haoyu Pei7Rui Li8Huan Luo9Deyu Zuo10Han She11Qingxiang Mao12Department of Anesthesiology, Daping Hospital, Army Medical UniversityDepartment of Anesthesiology, Daping Hospital, Army Medical UniversityDepartment of Anesthesiology, Daping Hospital, Army Medical UniversityDepartment of Anesthesiology, Daping Hospital, Army Medical UniversityDepartment of Anesthesiology, Daping Hospital, Army Medical UniversityDepartment of Anesthesiology, Daping Hospital, Army Medical UniversityDepartment of Anesthesiology, Daping Hospital, Army Medical UniversityDepartment of Anesthesiology, Daping Hospital, Army Medical UniversityDepartment of Anesthesiology, Daping Hospital, Army Medical UniversityDepartment of Critical Care Medicine, Chongqing General Hospital, Chongqing UniversityDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing University of Chinese Medicine, Chongqing Traditional Chinese Medicine HospitalDepartment of Anesthesiology, Daping Hospital, Army Medical UniversityDepartment of Anesthesiology, Daping Hospital, Army Medical UniversityAbstract Background Sepsis is a systemic inflammatory syndrome that can cause coagulation abnormalities, leading to damage in multiple organs. Vascular endothelial cells (VECs) are crucial in the development of sepsis-induced coagulopathy (SIC). The role of Parthenolide (PTL) in regulating SIC by protecting VECs remains unclear. Methods The study utilized septic rats and lipopolysaccharide (LPS)-stimulated VECs to simulate a SIC model and observe the therapeutic effects of PTL. Additionally, nanotechnology was employed to produce Nano-PTL (N-PTL), to observe whether it has advantages over PTL in treating SIC. Results PTL has been shown to mitigate lung injury in septic rats, significantly reduce tumor necrosis factor-α (TNF-α) levels, and increase survival rates. PTL treatment also enhances coagulation function, augments vascular endothelial cell (VEC) function, reduces mitochondrial fragmentation, and increases both mitochondrial oxygen consumption rate (OCR) and mitochondrial membrane potential (MMP), while inhibiting reactive oxygen species (ROS) production. By increasing BRD4/BCL-xL levels, PTL can prevent mitochondrial-mediated apoptosis in VECs, improve VEC function, and consequently ameliorate SIC. Additionally, nanotechnology-synthesized N-PTL further enhances the protective effects on VECs and coagulation function. Conclusions This study clarifies the therapeutic effects and mechanisms of PTL on SIC, offering new strategies and directions for the treatment of sepsis.https://doi.org/10.1186/s12967-025-06114-0Sepsis-induced coagulopathyVascular endothelial cellsParthenolideMitochondriaApoptosis |
| spellingShingle | Jun Zhang Xing Zhu Yong Li Yinyu Wu Yunxia Du Hai Yang Zhengchao Liu Haoyu Pei Rui Li Huan Luo Deyu Zuo Han She Qingxiang Mao Parthenolide improves sepsis-induced coagulopathy by inhibiting mitochondrial-mediated apoptosis in vascular endothelial cells through BRD4/BCL-xL pathway Journal of Translational Medicine Sepsis-induced coagulopathy Vascular endothelial cells Parthenolide Mitochondria Apoptosis |
| title | Parthenolide improves sepsis-induced coagulopathy by inhibiting mitochondrial-mediated apoptosis in vascular endothelial cells through BRD4/BCL-xL pathway |
| title_full | Parthenolide improves sepsis-induced coagulopathy by inhibiting mitochondrial-mediated apoptosis in vascular endothelial cells through BRD4/BCL-xL pathway |
| title_fullStr | Parthenolide improves sepsis-induced coagulopathy by inhibiting mitochondrial-mediated apoptosis in vascular endothelial cells through BRD4/BCL-xL pathway |
| title_full_unstemmed | Parthenolide improves sepsis-induced coagulopathy by inhibiting mitochondrial-mediated apoptosis in vascular endothelial cells through BRD4/BCL-xL pathway |
| title_short | Parthenolide improves sepsis-induced coagulopathy by inhibiting mitochondrial-mediated apoptosis in vascular endothelial cells through BRD4/BCL-xL pathway |
| title_sort | parthenolide improves sepsis induced coagulopathy by inhibiting mitochondrial mediated apoptosis in vascular endothelial cells through brd4 bcl xl pathway |
| topic | Sepsis-induced coagulopathy Vascular endothelial cells Parthenolide Mitochondria Apoptosis |
| url | https://doi.org/10.1186/s12967-025-06114-0 |
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