Optimization of Naringenin-loaded nanoparticles for targeting of Vanin-1, iNOS, and MCP-1 signaling pathway in HFD-induced obesity

Int J Pharm. 2024 Apr 10:654:123967. doi: 10.1016/j.ijpharm.2024.123967. Epub 2024 Mar 2.

Abstract

Naringenin, a natural dihydrochalcone flavonoid, exhibits diverse pharmacological properties. This study investigates the hypolipidemic effects of Nar-NPs on obese mice. The characteristics of Nar-NPs, including morphology, particle size, zeta potential, UV-vis, and FT-IR spectra, were examined. The anti-obesity properties of Nar-NPs were evaluated in obese rats, considering LD50, 1/20 LD50, and 1/50 LD50 for treatment preparation. Results indicated that synthesized Nar-NPs were uniform, spherical, and well-dispersed, with a size of 130.06 ± 1.98 nm and with a zeta potential of -25.6 ± 0.8 mV. Nar-NPs exhibited enhancement in the cumulative release of naringenin (56.87 ± 2.45 %) as compared to pure naringenin suspension 87.83 ± 1.84 % in 24 h of the study. The LD50 of Nar-NPs was determined as 412.5 mg/kg.b.w. HFD induced elevated glycemic, oxidative stress, and inflammatory biomarkers while reducing HDL-C, GSH, and superoxide dismutase (SOD) levels. Administration of Nar-NPs significantly mitigated body weight, glucose, insulin, leptin, TC, TG, SREBP1c, pAMPK, PPAR-α, as well as vanin-1, MCP-1, and iNOS mRNA gene expression. Histological investigations supported the biochemical and PCR findings. In a nutshell, the study suggests that the Nar-NPs could serve as a promising and viable pharmacological strategy for the treatment of obesity-related disorders.

Keywords: Insulin; Leptin; MCP-1 and iNOS; Naringenin Nanospanlastics; Obesity; Vanin-1.

MeSH terms

  • Animals
  • Flavanones* / chemistry
  • Flavanones* / pharmacology
  • Mice
  • Nanoparticles* / chemistry
  • Obesity / drug therapy
  • Rats
  • Signal Transduction
  • Spectroscopy, Fourier Transform Infrared

Substances

  • naringenin
  • Flavanones