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Verbenalin alleviates acute lung injury induced by sepsis and IgG immune complex through GPR18 receptor.
Yang, Lei; Liu, Tianyu; Zhuo, Yuzhen; Li, Dongmei; Li, Dihua; Liu, Junhong; Gao, Hejun; Zhang, Lanqiu; Lin, Jianping; Wang, Ximo.
Afiliación
  • Yang L; Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin, China.
  • Liu T; Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin, China; Graduate School, Tianjin Medical University, Tianjin, China.
  • Zhuo Y; Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin, China.
  • Li D; College of Pharmacy, Nankai University, Tianjin, China.
  • Li D; Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin, China.
  • Liu J; Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin, China.
  • Gao H; Graduate School, Tianjin Medical University, Tianjin, China.
  • Zhang L; Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin, China. Electronic address: lanqiuzhang@126.com.
  • Lin J; College of Pharmacy, Nankai University, Tianjin, China. Electronic address: jianpinglin@nankai.edu.cn.
  • Wang X; Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin, China; Graduate School, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Integ
Cell Signal ; 109: 110768, 2023 09.
Article en En | MEDLINE | ID: mdl-37315751
Acute lung injury is significantly associated with the aberrant activation and pyroptosis of alveolar macrophages. Targeting the GPR18 receptor presents a potential therapeutic approach to mitigate inflammation. Verbenalin, a prominent component of Verbena in Xuanfeibaidu (XFBD) granules, is recommended for treating COVID-19. In this study, we demonstrate the therapeutic effect of verbenalin on lung injury through direct binding to the GPR18 receptor. Verbenalin inhibits the activation of inflammatory signaling pathways induced by lipopolysaccharide (LPS) and IgG immune complex (IgG IC) via GPR18 receptor activation. The structural basis for verbenalin's effect on GPR18 activation is elucidated through molecular docking and molecular dynamics simulations. Furthermore, we establish that IgG IC induces macrophage pyroptosis by upregulating the expression of GSDME and GSDMD through CEBP-δ activation, while verbenalin inhibits this process. Additionally, we provide the first evidence that IgG IC promotes the formation of neutrophil extracellular traps (NETs), and verbenalin suppresses NETs formation. Collectively, our findings indicate that verbenalin functions as a "phytoresolvin" to promote inflammation regression and suggests that targeting the C/EBP-δ/GSDMD/GSDME axis to inhibit macrophage pyroptosis may represent a novel strategy for treating acute lung injury and sepsis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sepsis / Lesión Pulmonar Aguda / COVID-19 Límite: Humans Idioma: En Revista: Cell Signal Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sepsis / Lesión Pulmonar Aguda / COVID-19 Límite: Humans Idioma: En Revista: Cell Signal Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido