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

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.