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Background <p>Obesity, characterized by lipid accumulation, oxidative stress, and inflammation, remains a major public health challenge. This study aimed to investigate the therapeutic efficacy of diosgenin-loaded silver nanoparticles (Dio-AgNPs) in modulating obesity-induced metabolic and molecular dysfunction through integrated biochemical, gene expression, and molecular docking approaches.</p> Methods <p>Male albino rats were randomly assigned to control and experimental groups, with Dio-AgNPs administered at two distinct doses. Dio-AgNPs were synthesized and characterized using UV-Vis spectroscopy, TEM, DLS, and zeta potential measurements to confirm particle size and stability. Biochemical analyses included serum lipid profile (triglycerides, total cholesterol, LDL-c, HDL-c), fasting glucose, insulin levels, and HOMA-IR for insulin sensitivity. Oxidative stress markers (MDA) and antioxidant enzymes (SOD, CAT, GPx) were measured spectrophotometrically. Inflammatory cytokines (TNF-α and IL-6) were quantified by ELISA. Gene expression of lipogenic enzymes (<i>ACC</i> and <i>FAS</i>) and antioxidant-related genes was assessed using quantitative real-time PCR (qRT-PCR). Molecular docking simulations were performed to evaluate diosgenin’s binding affinities and interactions with ACC and FAS enzyme active sites.</p> Results <p>Dio-AgNP-treated rats showed significant reductions in serum triglycerides, total cholesterol, LDL-c, and fasting glucose compared to controls, while HDL-c and insulin sensitivity were markedly improved. Antioxidant enzyme activities (SOD, CAT, GPx) increased significantly, and MDA levels decreased, indicating oxidative stress attenuation. ELISA confirmed reduced levels of TNF-α and IL-6, revealing anti-inflammatory effects. Gene expression analysis demonstrated dose-dependent downregulation of <i>ACC</i> and <i>FAS</i>, along with upregulation of antioxidant and insulin-responsive genes. Molecular docking results revealed strong binding interactions of diosgenin with both ACC and FAS enzymes, supporting enzymatic inhibition and the transcriptional trends observed. Silver nanoparticle delivery enhanced bioavailability and target specificity.</p> Conclusion <p>This is the first report, to our knowledge, that combines biochemical, gene expression, and molecular docking data to investigate Dio-AgNPs’ anti-obesity effects. The findings highlight a promising nanomedicine-based approach for metabolic regulation and pave the way for further research in therapeutic nanoparticle design and application.</p>

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Diosgenin-Loaded Silver Nanoparticles Mitigate Obesity-Related Metabolic Dysfunction: an Integrative Analysis of Biochemical, Transcriptional, and Molecular Docking Evidence

  • 期刊论文

  • 发表日期：

    2026年1月12日

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  • Rasha Mohamed,
  • Mohammed Hussein,
  • El Sayed El Tamany,
  • Nasser Mostafa,
  • Ahmed Abbas

摘要

Background

Obesity, characterized by lipid accumulation, oxidative stress, and inflammation, remains a major public health challenge. This study aimed to investigate the therapeutic efficacy of diosgenin-loaded silver nanoparticles (Dio-AgNPs) in modulating obesity-induced metabolic and molecular dysfunction through integrated biochemical, gene expression, and molecular docking approaches.

Methods

Male albino rats were randomly assigned to control and experimental groups, with Dio-AgNPs administered at two distinct doses. Dio-AgNPs were synthesized and characterized using UV-Vis spectroscopy, TEM, DLS, and zeta potential measurements to confirm particle size and stability. Biochemical analyses included serum lipid profile (triglycerides, total cholesterol, LDL-c, HDL-c), fasting glucose, insulin levels, and HOMA-IR for insulin sensitivity. Oxidative stress markers (MDA) and antioxidant enzymes (SOD, CAT, GPx) were measured spectrophotometrically. Inflammatory cytokines (TNF-α and IL-6) were quantified by ELISA. Gene expression of lipogenic enzymes (ACC and FAS) and antioxidant-related genes was assessed using quantitative real-time PCR (qRT-PCR). Molecular docking simulations were performed to evaluate diosgenin’s binding affinities and interactions with ACC and FAS enzyme active sites.

Results

Dio-AgNP-treated rats showed significant reductions in serum triglycerides, total cholesterol, LDL-c, and fasting glucose compared to controls, while HDL-c and insulin sensitivity were markedly improved. Antioxidant enzyme activities (SOD, CAT, GPx) increased significantly, and MDA levels decreased, indicating oxidative stress attenuation. ELISA confirmed reduced levels of TNF-α and IL-6, revealing anti-inflammatory effects. Gene expression analysis demonstrated dose-dependent downregulation of ACC and FAS, along with upregulation of antioxidant and insulin-responsive genes. Molecular docking results revealed strong binding interactions of diosgenin with both ACC and FAS enzymes, supporting enzymatic inhibition and the transcriptional trends observed. Silver nanoparticle delivery enhanced bioavailability and target specificity.

Conclusion

This is the first report, to our knowledge, that combines biochemical, gene expression, and molecular docking data to investigate Dio-AgNPs’ anti-obesity effects. The findings highlight a promising nanomedicine-based approach for metabolic regulation and pave the way for further research in therapeutic nanoparticle design and application.