Ameliorative Effect of Red Grape Leaf Extract on Insulin Resistance: In Vivo And In Silico Studies

Naglaa M. Hamdy ^{1, 2*}, Hanan M. El-Tantawy ¹

Red grape leaf extract contains polyphenols, particularly resveratrol, which can potentially control insulin resistance and non-alcoholic fatty liver disease.

Abstract

Background: The prevalence of insulin resistance and non-alcoholic fatty liver disease (NAFLD) necessitates exploring natural remedies. Grape leaf extract (GLE), containing resveratrol and other polyphenols, shows potential in managing these conditions. The study aimed to investigate the secondary metabolites present in grape leaf extract (GLE), especially resveratrol. Method: Red grape leaves were collected from South Sinai, Egypt, and subjected to ultra-sonication for polyphenol extraction. High-performance liquid chromatography (HPLC) identified six polyphenols, with resveratrol being predominant. Thirty male Sprague Dawley rats were fed a high-fat diet to induce NAFLD. Rats were divided into groups, including GLE-treated and control groups. Biochemical parameters were measured to assess GLE's impact. Molecular docking was performed to understand resveratrol's mechanism of action on insulin resistance and liver dysfunction. Results: HPLC revealed significant levels of resveratrol in GLE. GLE (50%) exhibited control over blood glucose (mg/dl) (94.69 ± 3.16), insulin levels (μIU/ml) (16.80 ± 2.5), and improved insulin resistance HOMA-IR (3.9 ± 1.19). It also lowered liver enzymes such as ALT (45.20 ± 3.31), AST (59.60 ± 2.40), and ALP (335.10 ± 11.01 U/L) and improved lipid profiles (mg/dl), including cholesterol (90±10.2), triglycerides (66.21±4.0), HDL (40.10±3.5), and LDL (50.15±8.0). Molecular docking showed resveratrol's affinity for SIRT-1 and phosphodiesterases, indicating its role in regulating insulin resistance and liver function. Conclusion: GLE, particularly resveratrol, demonstrated synergistic effects in improving insulin resistance and hyperlipidemic liver in rats. It also exhibited hepatoprotective properties. Molecular docking highlighted resveratrol's potential mechanisms, making it a promising therapeutic candidate for managing insulin resistance and NAFLD.

Keywords: Red Grape Leaf Extract, Insulin Resistance, Non-Alcoholic Fatty Liver Disease, Situiin-1 Molecular Docking.

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