Quercetin improves contrast-induced acute kidney injury through the HIF-1α/lncRNA NEAT1/HMGB1 pathway

Pharm Biol. 2022 Dec;60(1):889-898. doi: 10.1080/13880209.2022.2058558.

Abstract

Context: The risk of contrast-induced acute kidney injury (CI-AKI) is increasing and the harm is great. Quercetin is the main active component in Abelmoschus manihot (L.) Medik (Malvaceae) and was reported to reduce the expression of HIF-1α.

Objective: We investigate whether quercetin improves the CI-AKI through the HIF-1α/lncRNA NEAT1/HMGB1 pathway.

Materials and methods: HK-2 cells were treated with iohexol (200 mg/mL) for 6 h to establish a CI-AKI model. Quercetin (20 μM) was administered to CI-AKI cells cultured in dishes for 24 h. Cell morphology was observed by a fluorescence microscope. MTT and TUNEL assays were used to detect cell survival rate and apoptosis. Relative mRNA levels were measured by qRT-PCR. Protein levels were detected using western blotting. IL-6 and TNF-α protein levels were tested by Elisa assay. Targeting binding sites of HIF-1α and lncRNA NEAT1 were detected by luciferase assay.

Results: The IC50 value of quercetin was 163.25 μM. The expression levels of HIF-1α, lncRNA NEAT1 and HMGB1 were upregulated in the CI-AKI cell model. Quercetin diminished cell injury and apoptosis via inhibiting HIF-1α. Silencing of HIF-1α targeting lncRNA MEAT1 diminished cell injury and apoptosis. Silencing lncRNA NEAT1 has the same effect via suppressing HMGB1 expression. Collectively, quercetin diminished cell injury and apoptosis in CI-AKI cell model via the inhibition of HIF-1α on lncRNA NEAT1/HMGB1 signalling pathway.

Discussion and conclusions: Quercetin diminished cell injury and apoptosis in CI-AKI cell mode via the inhibition of HIF-1α on the lncRNA NEAT1/HMGB1 signalling pathway, offering a potential novel therapeutic target for CI-AKI therapy.

Keywords: CI-AKI cell model; HuangKui; NEAT1; cell injury and apoptosis.

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / prevention & control
  • Apoptosis
  • HMGB1 Protein* / genetics
  • Humans
  • MicroRNAs* / genetics
  • Quercetin / pharmacology
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • HMGB1 Protein
  • MicroRNAs
  • RNA, Long Noncoding
  • Quercetin

Grants and funding

This work was supported by National Natural Science Foundation of China (No.81804079) and Natural Science Foundation of Hunan Province (No.2017JJ3442).