期刊
MOLECULES
卷 22, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/molecules22101683
关键词
AKI; pyranochalcone; derivative; anti-inflammation; TLR4; NF-kappa B
资金
- Natural Science Foundation of China [81570668]
Treatment of septic acute kidney injury (AKI) has still been beyond satisfaction, although anti-inflammatory therapy is beneficial for sepsis-induced AKI. Compound 5b was derived from natural pyranochalcones and exhibited potent anti-inflammatory activity in adjuvant-induced arthritis. In this study, we aimed to investigate the renoprotective effects and potential mechanism of 5b against lipopolysaccharide (LPS)-induced AKI. C57BL/6 mice and human renal proximal tubule cell line (HK-2 cell) were treated with LPS, respectively. Compound 5b was orally administrated at a dose of 25 mg/kg/day for 5 days before LPS (10 mg/kg) intraperitoneal injection. Cells were pretreated with 25 mu g/mL 5b for 30 min before LPS (1 mu g/mL) treatment. Pretreatment with 5b markedly alleviated tubular injury and renal dysfunction in LPS-induced AKI. The expression of IL-1 beta,IL-6, and TNF-alpha both in renal tissue of AKI mice and in the LPS-stimulated HK-2 cell culture medium were reduced by 5b treatment (p < 0.05). The results of immunohistochemistry staining showed that 5b reduced the expression of NF-kappa B p65 in kidneys. Similarly, 5b decreased the LPS-induced levels of NF-kappa B p65 and TLR4 proteins in kidneys and HK-2 cells. These data demonstrated that a potent pyranochalcone derivative, 5b, exhibited renoprotective effect against LPS-induced AKI, which was associated with anti-inflammatory activity by inhibiting the TLR4/NF-kappa B pathway.
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