Danlou tablet alleviates sepsis-induced acute lung and kidney injury by inhibiting the PARP1/HMGB1 pathway
Yongjing Yu,
Zhixi Li,
Chang Liu,
Yue Bu,
Weidong Gong,
Juan Luo,
Ziyong Yue
Affiliations
Yongjing Yu
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, China; The Key Laboratory of Anesthesiology and Intensive Care Research of Heilongjiang Province, 246 Xuefu Road, Harbin, 150001, China; The Key Laboratory of Myocardial Ischemia Organization, Chinese Ministry of Education, 246 Xuefu Road, Harbin, 150001, China
Zhixi Li
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, China; The Key Laboratory of Anesthesiology and Intensive Care Research of Heilongjiang Province, 246 Xuefu Road, Harbin, 150001, China; The Key Laboratory of Myocardial Ischemia Organization, Chinese Ministry of Education, 246 Xuefu Road, Harbin, 150001, China
Chang Liu
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, China; The Key Laboratory of Anesthesiology and Intensive Care Research of Heilongjiang Province, 246 Xuefu Road, Harbin, 150001, China; The Key Laboratory of Myocardial Ischemia Organization, Chinese Ministry of Education, 246 Xuefu Road, Harbin, 150001, China
Yue Bu
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, China; The Key Laboratory of Anesthesiology and Intensive Care Research of Heilongjiang Province, 246 Xuefu Road, Harbin, 150001, China; Department of Pain Medicine, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, China
Weidong Gong
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, China; The Key Laboratory of Anesthesiology and Intensive Care Research of Heilongjiang Province, 246 Xuefu Road, Harbin, 150001, China
Juan Luo
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, China; The Key Laboratory of Anesthesiology and Intensive Care Research of Heilongjiang Province, 246 Xuefu Road, Harbin, 150001, China
Ziyong Yue
Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, China; The Key Laboratory of Anesthesiology and Intensive Care Research of Heilongjiang Province, 246 Xuefu Road, Harbin, 150001, China; Corresponding author. Department of Anesthesiology, Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Harbin, 150001, China.
Background: Sepsis-associated acute lung injury (ALI) and acute kidney injury (AKI) are common complications that significantly impact patient prognosis. Danlou tablet (DLT) is a traditional herbal preparation with anti-inflammatory and antioxidant properties. However, its therapeutic potential in sepsis remains unknown. Methods: The impact of DLT on ALI and AKI was evaluated using the cecal ligation and puncture (CLP) experimental sepsis animal model. The effects of DLT on macrophages were observed through LPS-stimulated RAW264.7 cell line. Inflammatory cytokines, oxidative stress indicators, HE, PAS, and DHE staining, lung wet-to-dry weight ratio, and serum creatinine and urea nitrogen levels were used to assess tissue injury. Network pharmacology, molecular docking, and molecular dynamics simulations were used to explore the potential regulatory mechanisms of DLT in sepsis. Western blot and immunohistochemical staining were used to validate the expression of mechanism-related proteins. Results: DLT inhibited the inflammatory response and oxidative stress, improved structural and functional abnormalities in lung and kidney tissues in CLP mice, and alleviated pro-inflammatory responses of LPS-stimulated macrophages. PARP1 and HMGB1 were identified as key regulatory targets. The results of in vitro and in vivo experiments suggest that DLT can effectively inhibit PARP1/HMGB1 and improve sepsis-associated ALI and AKI. Conclusion: The present study demonstrated that DLT suppressed pro-inflammatory responses of macrophage and alleviated ALI and AKI in the CLP mice by inhibiting the transition activation of PARP1/HMGB1. These findings partially elucidate the mechanism of DLT in sepsis-associated ALI and AKI and further clarify the active components of DLT, thereby providing a scientific theoretical basis for treating sepsis with DLT.
