Ultrasound-assisted extraction of naringin from Exocarpium Citri Grandis using a novel ternary natural deep eutectic solvent based on glycerol: Process optimization using ANN-GA, extraction mechanism and biological activity

Sep 10, 2025Ultrasonics sonochemistry

Ultrasound extraction of naringin from citrus peel using a new natural solvent: Optimizing the process, how it works, and its biological effects

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Abstract

A high naringin extraction yield of 175.30 ± 2.94 mg/g was achieved using an optimized glycerol-based natural deep eutectic solvent.

The optimal extraction conditions were determined to be a temperature of 57 °C, a liquid-solid ratio of 25.9 mL/g, and a time of 24.4 minutes.
Structural changes in Exocarpium Citri Grandis were observed through scanning electron microscopy.
The activation energy for the extraction process was calculated at 40.45 kJ/mol.
Molecular dynamics simulations indicated improved solvation mechanisms during extraction.
The natural deep eutectic solvent maintained efficiency for at least three reuse cycles before significant decline occurred.
The extracted naringin showed inhibitory activity against key enzymes, with IC values of 19.6 μg/mL for α-glucosidase, 2.73 mg/mL for pancreatic lipase, and 1,086 μg/mL for acetylcholinesterase.

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This study aimed to develop an efficient green ultrasound-assisted extraction (UAE) method for naringin (Nar) from Exocarpium Citri Grandis (ECG) using a glycerol-based ternary natural deep eutectic solvent (NADES) and explore its biofunctional relevance. After screening and single-factor optimization, the optimal NADES was identified as glycerol:malic acid:propanedioic acid (1:1:2 M ratio, 30 % water content). Extraction conditions (liquid-solid ratio, temperature, time) were optimized via response surface methodology (RSM) and an artificial neural network-genetic algorithm (ANN-GA), with ANN-GA demonstrating superior predictive capability. Optimal parameters (57 °C, 25.9 mL/g, 24.4 min) yielded a high Nar extraction yield of 175.30 ± 2.94 mg/g. Scanning electron microscopy (SEM) revealed structural changes in ECG, while extraction kinetics indicated an activation energy of 40.45 kJ/mol and molecular dynamics simulations elucidated improved solvation mechanisms. NADES was reusable for at least three cycles before efficiency decreased significantly at the fourth reuse. Furthermore, the extracted Nar showed significant inhibitory activity against key enzymes, with ICvalues of 19.6 μg/mL (α-glucosidase), 2.73 mg/mL (pancreatic lipase), and 1,086 μg/mL (acetylcholinesterase). These results indicate its potential for hypoglycemic, hypolipidemic, and anti-Alzheimer's therapeutic effects. This work establishes a sustainable strategy for efficient Nar extraction, integrating green solvent technology with bioactivity assessment to advance its therapeutic potential. 50

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Ultrasound-assisted extraction of naringin from Exocarpium Citri Grandis using a novel ternary natural deep eutectic solvent based on glycerol: Process optimization using ANN-GA, extraction mechanism and biological activity

Abstract

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