Keluoxin inhibits the progression of Diabetic Kidney Disease via TNF-α/IKKβ/IκBα/NF-κB p65 signaling pathway.

ABSTRACT:

BACKGROUND

Previous clinical studies have indicated that Keluoxin can be used for the treatment of diabetic kidney disease. However, the specific mechanisms involved and the primary effective components have not been fully explored.

ABSTRACT: PURPOSE: The purpose of this study was to investigate the protective mechanisms of Keluoxin and its main components against diabetic kidney disease.

ABSTRACT:

METHODS

The animal models included db/db mice treated with Keluoxin or saline and db/m mice treated with saline. Astragaloside IV was used to treat human kidney-2 cells for in vitro experiments. To assess the effects of Keluoxin on diabetic kidney disease, serum biochemical parameters and tissue histopathological staining were examined. Western blotting and the quantitative real-time polymerase chain reaction were employed to detect the expression levels of fibrosis and inflammation markers. RNA sequencing was conducted on the samples, and downstream mechanisms were validated at the level of animal tissues and cells.

ABSTRACT:

RESULTS

Keluoxin significantly reduced blood glucose and urinary microalbumin in db/db mice, alleviated renal tubular damage, inflammation and fibrosis in diabetic kidney disease mice, and did not cause any damage to liver function. Sequencing results indicated that Keluoxin modulated the tumor necrosis factor signaling pathway, nuclear factor kappa light chain enhancer of activated B cell signaling pathway and inflammatory responses. In vivo experiments showed that Keluoxin inhibits the tumor necrosis factor alpha/inhibitor of kappa B kinase beta/inhibitor of nuclear factor kappa B alpha/nuclear factor kappa light chain enhancer of activated B cell p65 pathway, thereby providing protection against diabetic kidney disease. Immunoinfiltration analysis indicated that Keluoxin reduced neutrophil infiltration in the renal cortex of diabetic kidney disease mice. Through pharmacological component analysis, we determined that astragaloside IV is the main component of Keluoxin. In vitro experiments showed that astragaloside IV also alleviated the inflammatory response and fibrosis, inhibiting the expression of the tumor necrosis factor alpha/inhibitor of kappa B kinase beta/inhibitor of nuclear factor kappa B alpha/nuclear factor kappa light chain enhancer of activated B cell p65 signaling pathway.

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CONCLUSIONS

Keluoxin exerts renal protective effects by inhibiting the tumor necrosis factor alpha/inhibitor of kappa B kinase beta/inhibitor of nuclear factor kappa B alpha/nuclear factor kappa light chain enhancer of activated B cell p65 signaling pathway with astragaloside IV being the primary active component.