Lonicerin protects pancreatic acinar cells from caerulein-induced apoptosis, inflammation, and ferroptosis by activating the SIRT1/GPX4 signaling pathway

Toxicol Appl Pharmacol. 2024 Nov:492:117136. doi: 10.1016/j.taap.2024.117136. Epub 2024 Oct 29.

Abstract

Acute pancreatitis (AP) is a familiar emergency of digestive system characterized by pancreatic inflammation. Lonicerin (LCR) has been reported to exert anti-inflammatory and immunomodulatory characteristics in several inflammatory diseases. Nevertheless, its role and mechanism involved in AP are still unknown. This study was designed to explore the protective effect and potential mechanism of LCR in AP. In this study, LCR and ferrostatin-1 alleviated, but erastin aggravated caerulein (CAE) exposure-induced cytotoxicity and reduction of cell viability in AR42J cells. LCR exhibited a protective role in CAE-treated AR42J cells, as evidenced by alleviation of apoptosis, inflammation, and ferroptosis. Mechanistically, LCR decreased the phosphorylation level of nuclear factor-kappa B p65 and increased the levels of silent information regulator 1 (SIRT1) and glutathione peroxidase 4 (GPX4) in CAE-treated AR42J cells. Furthermore, functional rescue experiments manifested that knockdown of SIRT1 partially negated the inhibitory action of LCR against CAE-induced apoptosis, inflammation, and ferroptosis in AR42J cells. Overall, LCR mitigates apoptosis, inflammation, and ferroptosis in CAE-exposed AR42J cells, which is related to the activation of the SIRT1/GPX4 signaling pathway.

Keywords: Acute pancreatitis; Ferroptosis; Glutathione peroxidase 4; Lonicerin; Silent information regulator 1.

MeSH terms

  • Acinar Cells / drug effects
  • Acinar Cells / metabolism
  • Acinar Cells / pathology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Apoptosis* / drug effects
  • Cell Line
  • Ceruletide* / toxicity
  • Ferroptosis* / drug effects
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / pathology
  • Pancreatitis / chemically induced
  • Pancreatitis / metabolism
  • Pancreatitis / pathology
  • Phospholipid Hydroperoxide Glutathione Peroxidase* / metabolism
  • Rats
  • Signal Transduction* / drug effects
  • Sirtuin 1* / metabolism

Substances

  • Sirtuin 1
  • Ceruletide
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Sirt1 protein, rat
  • glutathione peroxidase 4, rat
  • Anti-Inflammatory Agents