Advanced Hybrid RSM-ANN-GA Modeling for Efficient Ultrasound-Assisted Hot-Water Extraction of Polyphenol-Rich Bioactives from Pilangkasa Fruit
Abstract
Pilangkasa (Ardisia elliptica Thunb.) is a source of natural antioxidants with potential applications. Ultrasound-assisted extraction (UAE) has been proposed as a sustainable alternative to conventional extraction methods, but extraction efficiency highly depends on processing conditions. Therefore, the present study was carried out to optimize the UAE of phytochemicals from polyphenol-rich fruit using Response Surface Methodology (RSM) and Artificial Neural Network-Genetic Algorithm (ANN-GA) modeling. A Box-Behnken design was used to study the effects of extraction temperature (50 to 70 °C), time (10 to 30 minutes), and ultrasonic power (50 to 70%) on the total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activities (DPPH and FRAP). The RSM models were highly predictive with coefficients of determination ranging from 85.52 to 98.71%. Among all the responses, extraction time was found to be the most influential factor. Results indicated that cavitation-enhanced mass transfer was the main factor influencing TPC and TFC, whereas antioxidant activity was greatly influenced by structural stability and the sonochemical degradation of polyphenols. The hybrid RSM-ANN-GA predicted the optimal conditions to be 60.2 °C, 22.45 minutes, and 60.34% ultrasonic power, resulting in TPC of 92.24 mg GAE g-1, TFC of 175.35 mg QE g-1, DPPH of 81.27%, and FRAP of 1.61 mg TE g-1. The ANN-GA model showed better prediction than RSM, with high correlation and slightly improved predicted optimal conditions. These results illustrate the potential of hybrid modeling approaches for optimizing extraction processes and provide insights into the physicochemical mechanisms underlying polyphenol recovery.
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Al Hasan, M. F., Sarkar, A., Miah, M. S., Jon, P. H., Alam, M., Albasher, G., & Ansari, M. J. (2025). Optimization of hybrid green extraction techniques for bioactive compounds from citrus lemon peel using response surface methodology (RSM) and artificial neural network (ANN). LWT, 230, 118273. https://doi.org/10.1016/j.lwt.2025.118273
Alara, O. R., Abdurahman, N. H., & Ukaegbu, C. I. (2021). Extraction of phenolic compounds: A review. Current Research in Food Science, 4, 200–214. https://doi.org/10.1016/j.crfs.2021.03.011
Aung, T., Kim, S. J., & Eun, J. B. (2022). A hybrid RSM-ANN-GA approach on optimisation of extraction conditions for bioactive component-rich laver (Porphyra dentata) extract. Food Chemistry, 366, 130689. https://doi.org/10.1016/j.foodchem.2021.130689
Awad, A. M., Kumar, P., Ismail-Fitry, M. R., Jusoh, S., Ab Aziz, M. F., & Sazili, A. Q. (2021). Green extraction of bioactive compounds from plant biomass and their application in meat as natural antioxidant. Antioxidants, 10(9), 1465. https://doi.org/10.3390/antiox10091465
Baliyan, S., Mukherjee, R., Priyadarshini, A., Vibhuti, A., Gupta, A., Pandey, R. P., & Chang, C. M. (2022). Determination of antioxidants by DPPH radical scavenging activity and quantitative phytochemical analysis of Ficus religiosa. Molecules, 27(4), 1326. https://doi.org/10.3390/molecules27041326
Benito-Román, Ó., Alonso, E., & Cocero, M. J. (2013). Ultrasound-assisted extraction of β-glucans from barley. LWT-Food Science and Technology, 50(1), 57–63. https://doi.org/10.1016/j.lwt.2012.07.006
Bitwell, C., Indra, S. S., Luke, C., & Kakoma, M. K. (2023). A review of modern and conventional extraction techniques and their applications for extracting phytochemicals from plants. Scientific African, 19, e01585. https://doi.org/10.1016/j.sciaf.2023.e01585
Castro-López, C., Ventura-Sobrevilla, J. M., González-Hernández, M. D., Rojas, R., Ascacio-Valdés, J. A., Aguilar, C. N., & Martínez-Ávila, G. C. (2017). Impact of extraction techniques on antioxidant capacities and phytochemical composition of polyphenol-rich extracts. Food Chemistry, 237, 1139–1148. https://doi.org/10.1016/j.foodchem.2017.06.032
Chemat, F., Rombaut, N., Sicaire, A. G., Meullemiestre, A., Fabiano-Tixier, A. S., & Abert-Vian, M. (2017). Ultrasound assisted extraction of food and natural products. Mechanisms, techniques, combinations, protocols and applications. A review. Ultrasonics Sonochemistry, 34, 540–560. https://doi.org/10.1016/j.ultsonch.2016.06.035
Chew, S. Y., Teoh, S. Y., Sim, Y. Y., & Nyam, K. L. (2021). Optimization of ultrasonic extraction condition for maximal antioxidant, antimicrobial, and antityrosinase activity from Hibiscus cannabinus L. leaves by using the single factor experiment. Journal of Applied Research on Medicinal and Aromatic Plants, 25, 100321. https://doi.org/10.1016/j.jarmap.2021.100321
Dung, N. C., Thuy, N. M., Giau, T. N., Van Hao, H., Van Thanh, N., Minh, V. Q., & Van Tai, N. (2026). Evaluation of quality characteristics, antioxidant activity, functional groups of sweet potato by-products and their usage in sandwich bread processing. Food Chemistry: X, 35, 103731. https://doi.org/10.1016/j.fochx.2026.103731
Fernandes, A., Mateus, N., & de Freitas, V. (2023). Polyphenol-dietary fiber conjugates from fruits and vegetables: Nature and biological fate in a food and nutrition perspective. Foods, 12(5), 1052. https://doi.org/10.3390/foods12051052
Giang, N. T. N., Tan, N. D., Ha, H. T. N., Van Thanh, D., Diem, L. T. T., Van Khai, T., & Quyen, D. K. (2025). Sustainable and novel approach for valorizing nutritional component in oyster mushrooms (Pleurotus sajor-caju) hydrolysates: An optimization study by ANN-GA. Journal of Agriculture and Food Research, 24, 102351. https://doi.org/10.1016/j.jafr.2025.102351
Gil-Martín, E., Forbes-Hernández, T., Romero, A., Cianciosi, D., Giampieri, F., & Battino, M. (2022). Influence of the extraction method on the recovery of bioactive phenolic compounds from food industry by-products. Food Chemistry, 378, 131918. https://doi.org/10.1016/j.foodchem.2021.131918
Gopan, V., Wins, K. L. D., & Surendran, A. (2018). Integrated ANN-GA approach for predictive modeling and optimization of grinding parameters with surface roughness as the response. Materials Today: Proceedings, 5(5), 12133–12141. https://doi.org/10.1016/j.matpr.2018.02.191
Gulcin, İ., & Alwasel, S. H. (2025). Fe3+ reducing power as the most common assay for understanding the biological functions of antioxidants. Processes, 13(5), 1296. https://doi.org/10.3390/pr13051296
Gürgen, A., Sevindik, M., Krupodorova, T., Korkmaz, A. F., Eraslan, E. C., & Akata, I. (2026). Optimization of Hymenopellis radicata extracts using RSM and ANN-GA and evaluation of biological activities. Scientific Reports, 16(1), 4696. https://doi.org/10.1038/s41598-025-34815-5
Hoo, D. Y., Low, D. Y. S., Tang, S. Y., Manickam, S., Tan, K. W., & Ban, Z. H. (2022). Ultrasonic cavitation: An effective cleaner and greener intensification technology in the extraction and surface modification of nanocellulose. Ultrasonics Sonochemistry, 90, 106176. https://doi.org/10.1016/j.ultsonch.2022.106176
Hu, L., Luo, Y., Yang, J., & Cheng, C. (2025). Botanical flavonoids: Efficacy, absorption, metabolism and advanced pharmaceutical technology for improving bioavailability. Molecules, 30(5), 1184. https://doi.org/10.3390/molecules30051184
Khoddami, A., Wilkes, M. A., & Roberts, T. H. (2013). Techniques for analysis of plant phenolic compounds. Molecules, 18(2), 2328–2375. https://doi.org/10.3390/molecules18022328
Kumar, S., Prajapati, V. K., Patel, A. K., Singh, S. R., & Nain, S. (2026). Extraction and characterization techniques for phenolic compounds from medicinal plants. Phenolic Compounds from Medicinal Plants: Pharmaceutical and Health Benefts (pp. 45–59). https://doi.org/10.1201/9781003527671-3
Loan, L. T. K., Thao, L. T. N., Mansamut, C., & Tai, N. V. (2025). Enhancing antioxidant extraction efficiency from red dragon fruit peel by green approach using novel optimization technique. Current Research in Green and Sustainable Chemistry, 11, 100474. https://doi.org/10.1016/j.crgsc.2025.100474
Loan, L. T. K., Thuy, N. M., & Tai, N. V. (2023). Ultrasound‐assisted extraction of antioxidant compounds from “Cẩm” purple rice bran for modulation of starch digestion. International Journal of Food Science, 2023(1), 1086185. https://doi.org/10.1155/2023/1086185
Md Yusof, N. A., Azhari, A. N., Nur Anati, Z. M. Z., & Roslan, N. R. (2025). Optimizing solvent selection for phytochemical extraction from Senna alata (L.) Roxb. leaves in Terengganu, Malaysia. Journal of Experimental Biology and Agricultural Sciences, 13(5), 716–725. https://doi.org/10.18006/2025.13(5).716.725
Nguyen, T. A., Bui, T. T. T., Nguyen, T. H., Dam, X. T., & Dang, H. T. (2026a). Artificial intelligence-assisted design of green-chemically treated banana fiber/epoxy composites for enhanced mechanical and fire-resistant performance. Polymer Bulletin, 83(2), 94. https://doi.org/10.1007/s00289-025-06106-6
Nguyen, T. A., Nguyen, T. T., & Dang, H. T. (2026b). Bio-nanopolyphenol coatings from Piper betle and Terminalia catappa on cotton cellulose: AI–RSM integrated optimization for enhanced UV and antibacterial performance. Cellulose, 33(6), 3639–3698. https://doi.org/10.1007/s10570-026-07024-0
Nguyen, T. A., Nguyen, T. T., & Nguyen, T. H. (2026c). Antibacterial and antifungal cotton fabrics functionalized with plant extracts for sustainable textile applications. Trends in Sciences, 23(8), 11670–11670. https://doi.org/10.48048/tis.2026.11670
Nguyen, T. A., Nguyen, X. H., & Nguyen, T. T. P. (2026d). AI-enhanced RSM optimization of green-treated spent coffee grounds for superior chromium (VI) removal. Trends in Sciences, 23(10), 12072–12072. https://doi.org/10.48048/tis.2026.12072
Osorio-Tobón, J. F. (2020). Recent advances and comparisons of conventional and alternative extraction techniques of phenolic compounds. Journal of Food Science and Technology, 57(12), 4299–4315. https://doi.org/10.1007/s13197-020-04433-2
Pappu, S. M. J., & Gummadi, S. N. (2017). Artificial neural network and regression coupled genetic algorithm to optimize parameters for enhanced xylitol production by Debaryomyces nepalensis in bioreactor. Biochemical Engineering Journal, 120, 136–145. https://doi.org/10.1016/j.bej.2017.01.010
Rifna, E. J., Misra, N. N., & Dwivedi, M. (2023). Recent advances in extraction technologies for recovery of bioactive compounds derived from fruit and vegetable waste peels: A review. Critical Reviews in Food Science and Nutrition, 63(6), 719–752. https://doi.org/10.1080/10408398.2021.1952923
Santos, M. P., Souza, M. C., Sumere, B. R., da Silva, L. C., Cunha, D. T., Bezerra, R. M. N., & Rostagno, M. A. (2019). Extraction of bioactive compounds from pomegranate peel (Punica granatum L.) with pressurized liquids assisted by ultrasound combined with an expansion gas. Ultrasonics Sonochemistry, 54, 11–17. https://doi.org/10.1016/j.ultsonch.2019.02.021
Shanmugam, G. (2025). Polyphenols: Potent protectors against chronic diseases. Natural Product Research, 39(23), 6941–6943. https://doi.org/10.1080/14786419.2024.2386402
Shehzadi, F., Shoaib, M., Munir, S., & Abdi, G. (2026). Ultrasound-assisted extraction of bioactive compounds from pomegranate peel and seed: A comprehensive review of key parameters and optimization strategies. Ultrasonics Sonochemistry, 124, 107722. https://doi.org/10.1016/j.ultsonch.2025.107722
Simsek, M., & Whitney, K. (2024). Examination of primary and secondary metabolites associated with a plant-based diet and their impact on human health. Foods, 13(7), 1020. https://doi.org/10.3390/foods13071020
Skenderidis, P., Petrotos, K., Giavasis, I., Hadjichristodoulou, C., & Tsakalof, A. (2017). Optimization of ultrasound assisted extraction of of goji berry (Lycium barbarum) fruits and evaluation of extracts’ bioactivity. Journal of Food Process Engineering, 40(5), e12522. https://doi.org/10.1111/jfpe.12522
Syamaladevi, R. M., Andrews, P. K., Davies, N. M., Walters, T., & Sablani, S. S. (2012). Storage effects on anthocyanins, phenolics and antioxidant activity of thermally processed conventional and organic blueberries. Journal of the Science of Food and Agriculture, 92(4), 916–924. https://doi.org/10.1002/jsfa.4670
Tabaraki, R., & Nateghi, A. (2011). Optimization of ultrasonic-assisted extraction of natural antioxidants from rice bran using response surface methodology. Ultrasonics Sonochemistry, 18(6), 1279–1286. https://doi.org/10.1016/j.ultsonch.2011.05.004
Teixeira, F., Silva, A. M., Sut, S., Dall'Acqua, S., Ramos, O. L., Ribeiro, A. B., ... & Rodrigues, F. (2024). Ultrasound-assisted extraction of bioactive compounds from goji berries: Optimization, bioactivity, and intestinal permeability assessment. Food Research International, 188, 114502. https://doi.org/10.1016/j.foodres.2024.114502
Thuy, N. M., Tien, V. Q., Giau, T. N., Van Hao, H., Minh, V. Q., & Van Tai, N. (2025). Bioactive compounds-rich Gac peel powder: Optimization of extraction and foam-mat drying conditions. Food and Humanity, 5, 100846. https://doi.org/10.1016/j.foohum.2025.100846
Van Tai, N., Minh, V. Q., & Thuy, N. M. (2023). Food processing waste in Vietnam: Utilization and prospects in food industry for sustainability development. Journal of Microbiology, Biotechnology and Food Sciences, 13(1), e9926–e9926. https://doi.org/10.55251/jmbfs.9926
Van Tai, N., Van Hao, H., Han, T. T. N., Giau, T. N., Thuy, N. M., & Van Thanh, N. (2024). Effect of foaming conditions and drying temperatures on total polyphenol content and drying rate of foam-mat dried banana powder: Modeling and optimization study. Journal of Agriculture and Food Research, 18, 101352. https://doi.org/10.1016/j.jafr.2024.101352
Vilkhu, K., Mawson, R., Simons, L., & Bates, D. (2008). Applications and opportunities for ultrasound assisted extraction in the food industry—A review. Innovative Food Science & Emerging Technologies, 9(2), 161–169. https://doi.org/10.1016/j.ifset.2007.04.014
Vinh, B. T., Loan, L. T. K., Mansamut, C., & Tai, N. V. (2026). Modeling the green extraction of bioactive compounds from Pilangkasa fruit (Ardisia elliptica Thunb) through empirical and machine learning approaches. Revista Mexicana de Ingeniera Quimica, 25(1), Proc26641. https://doi.org/10.24275/rmiq/Proc26641
Wang, L., Wang, Z., & Li, X. (2013). Optimization of ultrasonic‐assisted extraction of phenolic antioxidants from Malus baccata (Linn.) Borkh. using response surface methodology. Journal of Separation Science, 36(9–10), 1652–1658. https://doi.org/10.1002/jssc.201300062
Wanyo, P., Meeso, N., & Siriamornpun, S. (2014). Effects of different treatments on the antioxidant properties and phenolic compounds of rice bran and rice husk. Food Chemistry, 157, 457–463. https://doi.org/10.1016/j.foodchem.2014.02.061
Weremfo, A., Adulley, F., Dabie, K., Abassah-Oppong, S., & Peprah-Yamoah, E. (2022). Optimization of ultrasound-assisted extraction of phenolic antioxidants from turkey berry (Solanum torvum Sw) fruits using response surface methodology. Journal of Applied Research on Medicinal and Aromatic Plants, 30, 100387. https://doi.org/10.1016/j.jarmap.2022.100387
Yukongphan, P., Thitikornpong, W., Palanuvej, C., & Ruangrungsi, N. (2013). The pharmacognostic specification of Ardisia elliptica fruits and their embelin contents by TLC image analysis compared to TLC densitometry. Interprofessional Journal of Health Sciences, 11(2), 21–28. Retrieved from https://li05.tci-thaijo.org/index.php/IJHS/article/view/83
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