Acteoside alleviates UUO-induced inflammation and fibrosis by regulating the HMGN1/TLR4/TREM1 signaling pathway

PeerJ. 2023 Jan 18:11:e14765. doi: 10.7717/peerj.14765. eCollection 2023.

Abstract

Purpose: Acteoside (Act), a phenylethanoid compound that was first isolated from mullein, has been widely used for the investigation of anti-inflammatory and anti-fibrotic effect. However, the mechanism of Act against unilateral ureteral obstruction (UUO)-mediated renal injury is largely unknown. Therefore, this study aimed to explore the effects of Act on UUO rats and possible mechanisms.

Methods: A total of 20 Sprague-Dawley (SD) rats were divided randomly into three groups (n ≥ 6): (i) sham-operated group (Sham); (ii) UUO group (UUO+Saline); and (iii) UUO + Act 40 mg/kg/day, (UUO+Act); Continuous gavage administration for 2 weeks postoperatively, while the rats in Sham and UUO+saline groups were given equal amounts of saline. All rats were sacrificed after 14 days, the urine and blood samples were collected for biochemical analysis, the renal tissues were collected for pathological staining and immunohistochemistry. Correlations between individual proteins were analyzed by Pearson correlation analysis.

Results: The results of renal function indexes and histopathological staining showed that Act could improve renal function by reducing serum creatinine, blood urea nitrogen and urine protein at the same time, Act could alleviate renal inflammation and fibrosis. In addition, the results of immunohistochemistry showed that Act could reduce the expression of inflammation and kidney injury-related proteins F4/80, Mcp-1, KIM-1 proteins, as well as the expression of fibrosis-related protein α-SMA and β-catenin. More importantly, Act can also reduce the expression of HMGN1, TLR4 and TREM-1 proteins.

Conclusion: These data demonstrate that Act can ameliorate UUO-induced renal inflammation and fibrosis in rats probably through triggering HMGN1/TLR4/TREM-1 pathway.

Keywords: Acteoside; HMGN1; Inflammation; Obstructive nephropathy; Renal fibrosis.

MeSH terms

  • Animals
  • Fibrosis
  • HMGN1 Protein* / metabolism
  • Inflammation
  • Kidney Diseases* / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Toll-Like Receptor 4
  • Transcription Factors / pharmacology
  • Triggering Receptor Expressed on Myeloid Cells-1
  • Ureteral Obstruction* / metabolism

Substances

  • acteoside
  • HMGN1 Protein
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Transcription Factors
  • TREM1 protein, rat
  • Triggering Receptor Expressed on Myeloid Cells-1
  • HMGN1 protein, rat

Grants and funding

This work was supported by grants from the Special Fund for Basic Scientific Research Operating of Central Public Welfare Research Institutes, the Chinese Academy of Medical Sciences (2019PT320003), the Guizhou High-Level Innovative Talents Program (QKHPTRC(2018)5636-2), the Guizhou Clinical Research Center for Kidney Disease (QKHPTRC[2020]2201), the Science and Technology Fund project of Guizhou Provincial Health Commission in 2021 (gzwkj2021-136), the Youth Fund of Guizhou Provincial People’s Hospital in 2021 (GZSYQN[2021]12), and the Basic Research Plan of Guizhou Province in 2022 (Natural Science Project) (QKH-ZK[2022] General 265). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.