Esculentoside A ameliorates cecal ligation and puncture-induced acute kidney injury in rats

Abstract

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.

Emodin Attenuates Lipopolysaccharide-Induced Acute Liver Injury via Inhibiting the TLR4 Signaling Pathway in vitro and in vivo

“…The pharmacological effects of DEX mainly concentrated on anti-inflammatory ( Tolaj et al, 2017 ), immunosuppressive ( Wang et al, 2013 ), anti-endotoxic ( Zhang et al, 2017 ), and anti-shock ( Yang et al, 2010 ) effects. While researchers have demonstrated that DEX has shown the ability to enhance the resistance of organ injury and improve the outcome of infection, its limitation is that it cannot be used for a long time ( Kengatharan et al, 1996 ; Wang et al, 2013 ; Sun et al, 2017 ). Long-term use of glucocorticoids can cause many adverse effects, including weight gain, hyperglycemia, osteoporosis, cataracts, and increased risk of opportunistic infections.…”

The Effect of Overexpression of the Enhancer of Zeste Homolog 1 (EZH1) Gene on Aristolochic Acid-Induced Injury in HK-2 Human Kidney Proximal Tubule Cells In Vitro

“…Nuclear factor-κB (NF-κB) signaling is an important part of the innate immune signaling pathway, which is also involved in several key life processes, including inflammation and cell apoptosis [9–12]. Previously reported studies have shown that the suppression of the NF-κB signaling pathway attenuates induced acute renal injury, for example with lipopolysaccharide (LPS), and this signaling pathway may be relevant to the generation of AKI [13–17].…”

Chrysophanol Exerts Anti-inflammatory Activity by Targeting Histone Deacetylase 3 Through the High Mobility Group Protein 1-Nuclear Transcription Factor-Kappa B Signaling Pathway in vivo and in vitro

“…The therapeutic activity of DEX is attributed to its anti-inflammatory ( Tolaj et al, 2017 ), immunosuppressive ( Wang et al, 2013 ), anti-endotoxic ( Zhang et al, 2017 ), and anti-shock ( Yang et al, 2010 ) activity. Recent studies have determined that DEX possesses the capacity to activate the remission of organ injury and to overcome the infection, although the limitation of DEX treatment is that it is not recommended for long-term use, as it causes numerous adverse effects ( Wang et al, 2013 ; Sun et al, 2017 ). Thus, there is an urgent need to identify novel effective treatments for ALI having fewer secondary adverse effects.…”