Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-κB activities

Abstract

This study aimed to explore the effect and mechanisms of rhein on sepsis-induced acute kidney injury by injecting lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in vivo, and on LPS-induced HK-2 cells in vitro. For histopathological analysis, rhein effectively attenuated the severity of renal injury. Rhein could significantly decrease concentration of BUN and SCr and level of TNF-α and IL-1β in two different mouse models of experimental sepsis. Moreover, rhein could markedly attenuate circulating leukocyte infiltration and enhance phagocytic activity of macrophages partly impaired at 12 h after CLP. Rhein could enhance cell viability and suppresse the release of MCP-1 and IL-8 in LPS-stimulated HK-2 cells Furthermore, rhein down regulated the expression of phosphorylated NF-κB p65, IκBα and IKKβ stimulated by LPS both in vivo and in vitro. All these results suggest that rhein has protective effects on endotoxin-induced kidney injury. The underlying mechanism of rhein on anti-endotoxin kidney injury may be closely related with its anti-inflammatory and immunomodulatory properties by decreasing NF-κB activation through restraining the expression and phosphorylation of the relevant proteins in NF-κB signal pathway, hindering transcription of NF-κB p65.These evidence suggest that rhein has a potential application to treat endotoxemia-associated acute kidney injury.

Anthraquinones As Pharmacological Tools and Drugs

“…For example, emodin‐8‐ O ‐β‐glucoside from the traditional Chinese medicinal herb Polygonum cuspidatum is used for the treatment of acute hepatitis, and has shown in vivo and in vitro neuroprotective effects against cerebral ischemia‐reperfusion injury, and glutamate‐induced neuronal damage, respectively . Another example is rhein that showed potential for the treatment of endotoxin‐induced acute kidney injury mainly by inhibiting the activities of NF‐κB …”

“…95 Another example is rhein that showed potential for the treatment of endotoxin-induced acute kidney injury mainly by inhibiting the activities of NF-κB. 96…”

Salvianolic acid A attenuates kidney injury and inflammation by inhibiting NF-κB and p38 MAPK signaling pathways in 5/6 nephrectomized rats

“…As a model of CKD, 5/6 nephrectomized (5/6Nx) rats have been frequently used as to study the progression of CKD [10][11][12]. Lipopolysaccharide (LPS), a bacterial endotoxin, can trigger inflammatory responses by increasing the synthesis and release of pro-inflammatory cytokines [13]. HK-2 cells stimulated in vitro with LPS have been used to characterize the antiinflammatory effects of various compounds in the kidney [14,15].…”

“…Several pro-inflammatory cytokines and chemokines, including adhesion molecules such as tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1, CCL2), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are associated with the regulation of most inflammatory processes, which are collectively regulated by NF-κB [18,19]. Previous studies have shown that NF-κB is activated in human renal disease and various experimental models of renal inflammatory disease [13,20,21].…”

Quantum dot-based lateral-flow immunoassay for rapid detection of rhein using specific egg yolk antibodies

“…Rhein (RHE), also known as 1,8-dihydroxy-3-carboxy-anthraquinone, is believed to be the major constituent responsible for the pharmacological effects of Rheum officinale, which is one of the most popular medicinal materials in traditional Chinese medicine (TCM). Recent studies suggested that RHE exhibits antibacterial [1], antitumor [2] and anti-inflammatory properties [3], as well as a diuretic effect, with its intestineconverted product, RHE anthrone, exhibiting significant purgative activity. Previous research also indicated its potential nephrotoxicity or effects related to liver damage [4,5], suggesting that RHE use should be strictly controlled in clinical applications.…”