Salubrious effects of Ficus carica L. leaves extract in inflammation, diabetes, and obesity: An in-vitro, in-silico, and in-vivo study

Abstract

Various traditional medicinal systems have utilized the plant-based remedies for addressing the diverse ailments worldwide. Hence, this study aimed to scientifically explore the biological and phytochemical potential of <i>Ficus carica</i> L. leaves. This investigation encompassed the assessments of flavonoids, total phenolic contents, as well as physicochemical and phytochemical properties. Antioxidant potential was evaluated through hydrogen peroxide, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays, while anti-inflammatory effects were determined <i>via</i> proteinase inhibition, bovine serum albumin (BSA) denaturation, and heat-induced hemolysis assays. Additionally, antiglycation potential was assessed through free carbonyl group estimation, fructosamine, and Congo-red assays. The impact on diabetes mellitus, obesity, and renal and hepatic functions was investigated using the high-fat high-sugar diet model. Advanced analytical techniques including Fourier-transform infrared, high-performance liquid chromatography, and liquid chromatography-tandem mass spectrometry were employed to identify the active secondary metabolites present in the <i>F. carica</i> L. leaf extract. Molecular docking and absorption-distribution-metabolism-excretion-toxicity analyses were performed by different computational methods. Results revealed that substantial levels of total flavonoids (123 mg rutin equivalents/g) and phenolic content (333 mg gallic acid equivalent/g) along with promising antioxidant activity (IC₅₀: 0.58 mg/mL for DPPH assay, 35.6% inhibition for H₂O₂ assay, and FRAP value of 88.769 µg/g Fe₂SO₄ solution) were found. Notably, <i>F. carica</i> L. leaf extract exhibited the significant inhibition in heat-induced hemolysis (55 ± 0.03%), proteinase activity (28 ± 0.01%), and BSA denaturation (51.2 ± 0.05%). Furthermore, it exhibited the significant therapeutic effects on the biomarkers related to diabetes mellitus, obesity, liver, and kidney functions. Chemical analyses unveiled the presence of chlorogenic acid, ferulic acid, thymoquinone, rutin, coumarin, as well as terpenoids, alkaloids, coumarins, and flavonoids. The key findings suggest that <i>F. carica</i> L. leaf extract holds significant potential as an antioxidant, antidiabetic, and hypolipidemic agent.