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Molecules 2017, 22(10), 1683; doi:10.3390/molecules22101683

Anti-Inflammatory Pyranochalcone Derivative Attenuates LPS-Induced Acute Kidney Injury via Inhibiting TLR4/NF-κB Pathway

Kidney Research Institute, Division of Nephrology, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China
These authors contributed equally to this article.
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Received: 17 September 2017 / Revised: 1 October 2017 / Accepted: 4 October 2017 / Published: 10 October 2017
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Abstract

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 μg/mL 5b for 30 min before LPS (1 μg/mL) treatment. Pretreatment with 5b markedly alleviated tubular injury and renal dysfunction in LPS-induced AKI. The expression of IL-1β, IL-6, and TNF-α 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-κB p65 in kidneys. Similarly, 5b decreased the LPS-induced levels of NF-κB 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-κB pathway. View Full-Text
Keywords: AKI; pyranochalcone; derivative; anti-inflammation; TLR4; NF-κB AKI; pyranochalcone; derivative; anti-inflammation; TLR4; NF-κB
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MDPI and ACS Style

Shi, M.; Zeng, X.; Guo, F.; Huang, R.; Feng, Y.; Ma, L.; Zhou, L.; Fu, P. Anti-Inflammatory Pyranochalcone Derivative Attenuates LPS-Induced Acute Kidney Injury via Inhibiting TLR4/NF-κB Pathway. Molecules 2017, 22, 1683.

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