Mechanism of dioscin ameliorating renal fibrosis through NF‑κB signaling pathway‑mediated inflammatory response.

Abstract

Dioscin (DIS) is a natural compound derived from Chinese herbal medicine. In recent years, multiple studies have reported that DIS has immunoregulation, anti‑fibrosis, anti‑inflammation, anti‑viral and anti‑tumor effects. However, the mechanism by which DIS ameliorates renal fibrosis and inflammation remains to be elucidated. The aim of the present study was to investigate the role of DIS in renal fibrosis and inflammation and to explore its underlying mechanism. It used network pharmacology to predict the targets of DIS for the treatment of renal interstitial fibrosis. The present study was performed using unilateral ureteral obstruction mice and HK‑2 cells in vivo and in vitro. The mice were treated with different doses of DIS. Kidney tissues were collected for histopathology staining, western blotting, immunohistochemistry staining and reverse transcription‑quantitative (RT‑q) PCR. TGF‑β1 (2 ng/ml) was used to induce renal fibrosis in the cells. Then, cells were respectively treated with DIS (3.125, 6.25, 12.5 µM) and Bay11‑7082 (an inhibitor of NF‑κB p65 nuclear transcription, 1 µM) for another 24 h. The expressions of inflammatory factors and NF‑κB pathway proteins were detected by immunofluorescence, ELISA, western blotting and RT‑qPCR. DIS alleviated renal injury in the UUO mice. Mechanistically, DIS not only decreased the expressions of inflammatory factors including IL‑1β, NOD‑like receptor thermal protein domain associated protein 3, monocyte chemotactic protein 1, IL‑6, TNF‑α and IL‑18 but also reduced the level of phosphorylation of NF‑κB p65 in vivo and in vitro, which was similar to the impact of Bay11‑7082. DIS ameliorated renal fibrosis by inhibiting the NF‑κB signaling pathway‑mediated inflammatory response, which may be a therapeutic pathway for delaying chronic kidney disease.

• Authors: Yang Wang, Peng Liu, Guijie Ma, Chenguang Wu, Wenhui Zhu, Pengce Sun, Wenya Lu, Xinyu Yang, Yilun Zhang, Na Liu, Ping Li
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 27 Issue 4 (04 2023) ISSN: 1791-3004 [Electronic] Greece
• PMID: 36960871 (Publication Type: Journal Article)

Chemical References

• NF-kappa B
• 3-(4-methylphenylsulfonyl)-2-propenenitrile
• dioscin

Topics

• Mice
• Animals
• NF-kappa B (metabolism)
• Kidney Diseases (drug therapy, etiology, metabolism)
• Kidney (pathology)
• Signal Transduction
• Ureteral Obstruction (complications, drug therapy, metabolism)
• Inflammation (metabolism)
• Fibrosis