Optimization of Phloretin-loaded Nanospanlastics for Targeting of FAS/SREBP1c/AMPK/ OB-Rb Signaling Pathway in HFD-induced Obesity.

Objectives: Obese patients are at increased risk for CVD, which is the main cause of premature death and has been a major cause of disability and ill health in recent years. PTN, a natural dihydrochalcone flavonoid, has a variety of pharmacological characteristics. This article aimed to prepare PTN-NSLs to evaluate their anti-obesity activity.
Methods: Morphology, Particle size, zeta potential, UV-vis, entrapment efficiency, FT-IR spectra, and an in vitro release study of PTN-NSLs were described. PTN-NSLs were also tested for their anti-obesity properties in obese rats. The LD ₅₀ of PTN-NSLs was calculated, as was the 1/20 LD ₅₀ prepared for the treatment of obese rats. Also, the level of glycemic, oxidative stress and inflammatory biomarkers were estimated in the obese rat's model.
Results: The synthesized PTN-NSLs were uniform, spherically shaped, and well dispersed with no aggregation noted, with a size range of 114.06 ± 8.35 nm. The measured zeta potential value of PTN-NSLs was -32.50.8 mv. Also, the UV spectra of PTN and PTN-NSLs have strong absorption at 225 and 285 nm. Also, the LD ₅₀ of PTN-NSLs was found to be 2750 mg/kg.b.w. Moreover, administrating obese rats with PTN-NSLs resulted in improved glycemic features as well as GSH, SOD, GPx, GR, IL10, TBARs, and IL-6 levels, as well as attenuated FAS, SREBP1c, AMPK, ACO, CPT1, and OB-Rb gene expression.
Conclusion: Administration of PTN-NSLs significantly attenuated the levels of glycemic, oxidative stress, and inflammatory biomarkers. The biochemical and PCR findings are aided by histological investigations. Also, the present findings imply that PTN-NSLs might be a promising pharmacological tool for the treatment of obesity-related diseases.
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