Protective effects of lemon nanovesicles: evidence of the Nrf2/HO-1 pathway contribution from in vitro hepatocytes and in vivo high-fat diet-fed rats

Biomed Pharmacother. 2024 Nov:180:117532. doi: 10.1016/j.biopha.2024.117532. Epub 2024 Oct 8.

Abstract

The cross-talk between plant-derived nanovesicles (PDNVs) and mammalian cells has been explored by several investigations, underlining the capability of these natural nanovesicles to regulate several molecular pathways. Additionally, PDNVs possess biological proprieties that make them applicable against pathological conditions, such as hepatic diseases. In this study we explored the antioxidant properties of lemon-derived nanovesicles, isolated at laboratory (LNVs) and industrial scale (iLNVs) in human healthy hepatocytes (THLE-2) and in metabolic syndrome induced by a high-fat diet (HFD) in the rat. Our findings demonstrate that in THLE-2 cells, LNVs and iLNVs decrease ROS production and upregulate the expression of antioxidant mediators, Nrf2 and HO-1. Furthermore, the in vivo assessment reveals that the oral administration of iLNVs improves glucose tolerance and lipid dysmetabolism, ameliorates biometric parameters and systemic redox homeostasis, and upregulates Nrf2/HO-1 signaling in HFD rat liver. Consequently, we believe LNVs/iLNVs might be a promising approach for managing hepatic and dysmetabolic disorders.

Keywords: High-fat diet fed rats; Lemon-derived nanovesicles; Liver; Metabolic syndrome; Oxidative stress.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Cell Line
  • Citrus / chemistry
  • Diet, High-Fat* / adverse effects
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1* / metabolism
  • Hepatocytes* / drug effects
  • Hepatocytes* / metabolism
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Metabolic Syndrome / metabolism
  • NF-E2-Related Factor 2* / metabolism
  • Nanoparticles
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Signal Transduction* / drug effects

Substances

  • NF-E2-Related Factor 2
  • Heme Oxygenase-1
  • Antioxidants
  • Nfe2l2 protein, rat
  • Hmox1 protein, rat
  • Reactive Oxygen Species
  • Heme Oxygenase (Decyclizing)