Xuebijing injection alleviates septic acute kidney injury by modulating inflammation, mitochondrial dysfunction, and endoplasmic reticulum stress.

Abstract

Background: Xuebijing (XBJ) injection has been used to treat sepsis. However, the effect and mechanism of XBJ injection in the treatment of septic acute kidney injury (AKI) is unknown. This study aimed to explore the therapeutic effect of XBJ injection on septic AKI and elucidate its possible mechanisms.

Methods: Network pharmacological analysis was conducted using databases of GeneCards, TCMSP, SwissTargetPrediction and STRING. In vivo, a septic AKI model was established in C57BL/6 mice by cecal ligation and puncture (CLP). The groups were Sham, XBJ, CLP, and CLP + XBJ (10 mL/kg IV) (n = 5). Tubular damage, renal function, and levels of inflammation and apoptosis in the kidneys were evaluated. In vitro model was lipopolysaccharide (LPS, 100 μg/mL) stimulated HK-2 cells. The groups were PBS, XBJ, LPS, and LPS + XBJ (XBJ injected at 10 dilutions). Cell viability, apoptosis, inflammation, mitochondrial function and, endoplasmic reticulum (ER) stress were also assessed.

Results: Network pharmacological analysis identified Toll like receptor 4 (TLR4) as the core gene in XBJ against septic AKI, and the inflammatory response was the most enriched pathway. XBJ treatment significantly alleviated tubular damage in CLP mice by down-regulating serum creatinine (SCr), blood urea nitrogen (BUN), kidney injury molecule 1 (KIM1), and neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, both in vivo and in vitro experiments demonstrated that XBJ treatment could inhibit apoptosis, inflammation, mitochondrial dysfunction, and ER stress via TLR4/MyD88/NF-κB axis.

Conclusion: This study indicates that XBJ injection is a promising drug for the treatment of septic AKI.