Apigenin attenuates obesity-associated hepatic dysfunction and fibrosis in rats: an integrated biochemical, histological, and ex vivo dielectric study.

backgroundApigenin (APG), a naturally occurring flavonoid, has been widely reported to exert anti-inflammatory, antioxidant, and metabolic regulatory effects. However, its therapeutic impact on obesity-associated nonalcoholic fatty liver disease (NAFLD), particularly in relation to hepatic fibrosis and tissue biophysical properties, remains incompletely characterized. This study investigated the effects of APG on biochemical, histopathological, molecular, and dielectric characteristics of the liver in a diet-induced obese rat model.

methodsTwenty-four male rats were equally divided into 4 groups (n = 6/each).The first (control) and second (obese) groups were not treated while the obese rats in the third and fourth groups were given 25 and 50 mg/kg APG orally respectively for 6 weeks. Inflammatory markers, oxidative stress parameters and routine liver function tests were estimated. Moreover, histological study was performed. Broadband dielectric spectroscopy was applied ex vivo to characterize frequency-dependent dielectric properties of liver tissue following uniform fixation and dehydration protocols.

resultsAPG treatment was associated with a dose-dependent attenuation of hepatic signal transducer and activation of transcription 3 (STAT3) and its phosphorylated (p-STAT3) levels and a significant enhancement of nuclear factor erythroid 2–related factor 2 (NRF2) expression. These molecular changes were accompanied by reductions in plasma inflammatory markers, liver function enzyme levels, and body mass index (BMI) in obese rats. APG also significantly improved hepatic redox status, as indicated by increased glutathione (GSH) and superoxide dismutase (SOD) levels and reduced malondialdehyde (MDA), reflecting decreased lipid peroxidation. Histological analyses demonstrated marked reductions in hepatic steatosis and fibrosis in APG-treated groups. Dielectric spectroscopy revealed obesity-associated alterations in tissue dielectric behavior, including reduced dielectric constant and loss, increased real impedance, and altered conductivity across frequency ranges. APG administration partially to markedly restore these dielectric parameters toward control values in a dose-dependent manner, with the higher dose exhibiting the greatest degree of normalization in impedance spectra and Nyquist plot profiles.

conclusionsCollectively, these findings indicate that apigenin ameliorates obesity-induced hepatic dysfunction through coordinated improvements in inflammatory signaling, oxidative balance, and tissue architecture. Changes in dielectric properties were interpreted as associative biophysical signatures of structural and compositional tissue remodeling, rather than direct measures of in vivo membrane electrophysiology. Within these limits, dielectric spectroscopy emerges as a complementary, non-invasive biophysical approach for monitoring hepatic tissue alterations and therapeutic response in experimental NAFLD models.