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

## TL;DR

This study shows that Ficus carica L. leaves have strong antioxidant, anti-inflammatory, and health benefits for diabetes and obesity through various lab and computational tests.

## Contribution

The study combines in-vitro, in-silico, and in-vivo methods to demonstrate the therapeutic potential of Ficus carica L. leaf extract for multiple health conditions.

## Key findings

- Ficus carica L. leaf extract showed high levels of flavonoids and phenolics with strong antioxidant activity.
- The extract significantly inhibited heat-induced hemolysis, proteinase activity, and BSA denaturation.
- It exhibited therapeutic effects on diabetes, obesity, and organ function biomarkers.

## 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 Ficus carica 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 via 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 F. carica 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, F. carica 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 F. carica L. leaf extract holds significant potential as an antioxidant, antidiabetic, and hypolipidemic agent.