GALLIC ACID-LOADED PRONIOSOMES: FORMULATION AND EVALUATION IN HIGH-FAT DIET-INDUCED NON-ALCOHOLIC FATTY LIVER DISEASE

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic liver disorder associated with obesity, insulin resistance and dyslipidemia. Gallic acid (GA), a polyphenol with reported hepatoprotective, antioxidant and lipid modulating activity, has poor aqueous solubility and low oral bioavailability. We prepared GA-loaded proniosomes using Span 60 and evaluated them in a high-fat diet (HFD)-induced NAFLD model in male Wistar albino rats (Rattus norvegicus). Rats received an HFD (36% fat) for 120 days and were allocated to four groups (n = 6): normal control, disease control (HFD), positive control (saroglitazar, 4 mg/kg/day, orally) and test formulation (GA proniosomes, 150 mg/kg/day, orally), with treatment during the final 60 days. Body weight, fasting blood glucose, serum insulin, lipid profile, liver and adipose tissue weights and liver histology were assessed. Compared with the disease control group, GA proniosomes lowered fasting blood glucose (105.6 ± 16.12 mg/dL [5.86 ± 0.89 mmol/L] vs. 149.1 ± 28.55 mg/dL [8.28 ± 1.58 mmol/L]; P < 0.05) and serum triglycerides (101.0 ± 20.8 mg/dL [1.14 ± 0.23 mmol/L] vs. 184.4 ± 36.1 mg/dL [2.08 ± 0.41 mmol/L]; P < 0.05), and increased HDL cholesterol (33.30 ± 6.52 mg/dL [0.86 ± 0.17 mmol/L] vs. 17.70 ± 4.99 mg/dL [0.46 ± 0.13 mmol/L]; P < 0.05). Histology showed a mild decrease in macrovesicular steatosis in treated animals. Body weight, serum insulin, total cholesterol and liver weight did not differ significantly from the disease control group. Because no free GA group was included, the contribution of the proniosomal carrier to these effects could not be determined. These findings indicate that GA proniosomes improve glycemic and lipid parameters and mildly reduce macrovesicular steatosis in HFD-fed rats, and support further mechanistic evaluation, including gene expression analysis.