Esculentoside A (EsA), a saponin isolated from Phytolacca esculenta, can
attenuate acute liver and lung injury. However, whether EsA has a protective effect
against sepsis-induced acute kidney injury (AKI) has not been reported. In this study, EsA
(2.5, 5, or 10 mg/kg) was given to rats with sepsis induced by cecal ligation and puncture
(CLP). We found that EsA improved the survival of septic rats in a dose-dependent manner.
In addition, EsA lowered the kidney tubular damage score and decreased blood urea nitrogen
and creatinine. Moreover, EsA inhibited excessive generation of pro-inflammatory tumor
necrosis factor-α, IL-1β, and IL-6 in the serum and downregulated cyclooxygenase-2 and
inducible nitric oxide synthase in the renal tissues of septic rats. EsA also suppressed
the production of malonaldehyde and the activity of myeloperoxidase in the septic kidney
and enhanced the activity of superoxide dismutase and glutathione. The anti-inflammatory
and antioxidative effects of a high dose of EsA were comparable to those of dexamethasone.
Mechanically, EsA inhibited CLP-induced increases in high-mobility group box 1, Toll-like
receptor-4, and myeloid differentiation primary response 88 and nuclear accumulation of
nuclear factor kappa B p65 in renal tissues. In vitro,
lipopolysaccharide-induced alteration of AKI-related factors in HK-2 cells, which had been
evaluated in vivo, was inhibited after EsA administration. Taken
together, our study suggests that EsA effectively protects rats against septic AKI caused
by CLP.