Xijiao Dihuang Decoction Protects Against Murine Sepsis-Induced Cardiac Inflammation and Apoptosis via Suppressing TLR4/NF-κB and Activating PI3K/AKT Pathway

Abstract

Wei Li,1,* Mingrui Lin,1,* Jiapeng Li,2,* Qihang Ding,2 Xiaoling Chen,3 Huaiyu Chen,1 Zhiqing Shen,1 Xueli Zhu1 1The People’s Hospital of Fujian Traditional Medical University, Fuzhou, Fujian, People’s Republic of China; 2Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of China; 3Department of Infectious Disease, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiqing Shen; Xueli Zhu, Email [email protected]; [email protected]: Xijiao Dihuang decoction (XJDHT), a traditional Chinese medicine, is widely used to treat patients with sepsis. However, the mechanisms underlying the effects of XJDHT on cardiac dysfunction have yet to be fully elucidated. The present study evaluated the potential utility of XJDHT in protecting against sepsis-induced cardiac dysfunction and myocardial injury.Methods: The mice were randomly divided into 3 groups and administered Lipopolysaccharide (LPS,10 mg/kg) or equivalent saline solution (control) and treated with XJDHT (10 g/kg/day) or saline by gavage for 72 hours. XJDHT was dissolved in 0.9% sodium chloride and administered at 200 μL per mouse. Transthoracic echocardiography, RNA-seq, TUNEL assays and hematoxylin and eosin (H&E) staining of cardiac tissues were performed.Results: Treatment with XJDHT significantly enhanced myocardial function and attenuated pathological change, infiltration of inflammatory cells, levels of TNF-α, IL-1β and expression of TLR4 and NF-κB in mice with sepsis. RNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway analyses identified 531 differentially expressed genes and multiple enriched signaling pathways including the PI3K/AKT pathway. Further, XJDHT attenuated cardiac apoptosis and decreased Bax protein expression while increasing protein levels of Bcl-2, PI3K, and p-AKT in cardiac tissues of mice with sepsis.Conclusion: In summary, XJDHT improves cardiac function in a murine model of sepsis by attenuating cardiac inflammation and apoptosis via suppressing the TLR4/NF-κB pathway and activating the PI3K/AKT pathway. Keywords: XJDHT, sepsis, inflammation, apoptosis, TLR4/NF-κB, PI3K/AKT pathway

Keywords

• xjdht
• sepsis
• inflammation
• apoptosis
• tlr4/nf-κb
• pi3k/akt pathway