Modeling and Optimization of Ellagic Acid from Chebulae Fructus Using Response Surface Methodology Coupled with Artificial Neural Network

The dried ripe fruit of <i>Terminalia chebula</i> Retz. is a common Chinese materia medica, and ellagic acid (EA), isolated from the plant, is an important bioactive component for medicinal purposes. This study aimed to delineate the optimal extraction parameters for extracting the EA content from Chebulae Fructus (CF), focusing on the variables of ethanol concentration, extraction temperature, liquid-solid ratio, and extraction time. Utilizing a combination of the response surface methodology (RSM) and an artificial neural network (ANN), we systematically investigated these parameters to maximize the EA extraction efficiency. The extraction yields for EA obtained under the predicted optimal conditions validated the efficacy of both the RSM and ANN models. Analysis using the ANN-predicted data showed a higher coefficient of determination (<i>R</i>²) value of 0.9970 and a relative error of 0.79, compared to the RSM's 2.85. The optimal conditions using the ANN are an ethanol concentration of 61.00%, an extraction temperature of 77 °C, a liquid-solid ratio of 26 mL g^-1 and an extraction time of 103 min. These findings significantly enhance our understanding of the industrial-scale optimization process for EA extraction from CF.