XJDHT protects against sepsis-induced cardiac inflammation and apoptosis via suppression TLR4/NF-κB and activating PI3K/AKT pathway

Abstract

Abstract Purpose 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 dysfunctionhave 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 Mice administered Lipopolysaccharide (LPS,10 mg/kg) or equivalent saline solution (control) were treated with XJDHT (10 g/kg/day) or saline by gavage for 72 hours. 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 suppression the TLR4/NF-κB pathway and activating the PI3K/AKT pathway