Synergistic effect of curcumin and resveratrol on the prevention of contrast-induced nephropathy by suppressing inflammation via regulating signaling pathways of microRNA-17/TXNIP/NRLP3 and microRNA-30c/FOXO3/NRLP3

Biotechnol Appl Biochem. 2022 Feb 20. doi: 10.1002/bab.2333. Online ahead of print.

ABSTRACT

In this study, we aimed to explore the molecular mechanism underlying the effect of resveratrol (RES) and curcumin (CUR) on the treatment of CIN. And we also investigated the potential additive interactions between RES and CUR. Rat models were established as a Sham group, a contrast induced nephropathy (CIN) group, a CIN+RES group, a CIN+CUR group and a CIN+RES+CUR group. ELISA was performed to observe the expression levels of serum creatinine, blood urea nitrogen (BUN) and neutrophil gelatinase-associated lipocalin (NGAL) in the rats. H&E staining was performed to measure renal dysfunction of each rat group. Real-time PCR, Western blot, computational analysis and luciferase assays were used to establish the signaling pathways responsible for the effect of RES and CUR on CIN. The levels of serum creatinine, BUN and serum NGAL were significantly increased in CIN rats, which were recovered by the administration of RES and/or CUR. The high injury score in the CIN group was preserved by the administration of RES and CUR. The expression of both miR-17 and miR-30c was markedly decreased while the expression of thioredoxin-interacting protein (TXNIP), forkhead box O3 (FOXO3), NLR family pyrin domain containing 3 (NRLP3), interleukin-1 beta (IL-1β) and cleaved caspase-3 was all markedly increased in the CIN group. RES or CUR treatment mitigated the above dysregulation in CIN rats, and the combined administration of RES+CUR exhibited a more impressive effect. TXNIP was a target gene of miR-17, while FOXO3 was a target gene of miR-30c. The combined administration of RES and CUR additively reduced the expression of NLRP3, and attenuated renal injury and inflammation in CIN treatment. This article is protected by copyright. All rights reserved.

PMID:35184332 | DOI:10.1002/bab.2333