Statistical Modeling and Numerical Optimization of Ultrasound-Assisted Phenolic and Flavonoid Extraction from Momordica charantia Fruit

Authors

  • Tubagus Akmal Akademi farmasi Bumi Siliwangi Author
  • Cszahreyloren Vitamia Akademi farmasi Bumi Siliwangi Author
  • Andi Ika Julianti Handayani Akademi farmasi Bumi Siliwangi Author

DOI:

https://doi.org/10.30872/jtpc.v10i2.430

Abstract

This study modeled ultrasound-assisted extraction (UAE) of total phenolic content (TPC) and total flavonoid content (TFC) from Momordica charantia fruit using a three-factor Box–Behnken design. Ethanol concentration (0–96%), liquid-to-solid ratio (10–40 mL/g), and extraction time (5–30 min) were evaluated at a fixed bath temperature of 50 °C. Box–Cox-guided square-root and log₁₀ transformations were applied to TPC and TFC, respectively. The selected linear models were significant (p < 0.0001), with R²/adjusted R²/predicted R² of 0.9582/0.9469/0.9264 for TPC and 0.9129/0.8892/0.8148 for TFC. Liquid-to-solid ratio significantly affected TPC, whereas ethanol concentration and liquid-to-solid ratio significantly affected TFC; extraction time was not significant. TPC showed significant lack-of-fit (p = 0.0426), while TFC lack-of-fit was not significant (p = 0.0636). Joint numerical optimization predicted 95.994% ethanol, 40.000 mL/g, and 5.000 min (desirability = 0.955), with bias-corrected mean predictions of 109.054 mg GAE/g dry extract and 123.371 mg QE/g dry extract. This boundary solution was not experimentally confirmed. At a separate confirmation location (82.8208%, 37.4455 mL/g, 26.3205 min), TPC was substantially underpredicted, whereas TFC agreed more closely with the model. These findings identify a preliminary operating direction for UAE but indicate that the TPC model requires additional design points, stronger replication, and assay-specific verification before confirmatory or scale-up use.

Downloads

Download data is not yet available.

References

[1] S. Sur and R. B. Ray, “Bitter melon (Momordica charantia), a nutraceutical approach for cancer prevention and therapy,” Cancers (Basel)., vol. 12, no. 8, pp. 1–22, 2020, doi: 10.3390/cancers12082064.

[2] M. Muronga et al., “Three Selected Edible Crops of the Genus Momordica as Potential Sources of Phytochemicals: Biochemical, Nutritional, and Medicinal Values,” Front. Pharmacol., vol. 12, no. May, pp. 1–19, 2021, doi: 10.3389/fphar.2021.625546.

[3] T. Akmal and L. Sasongko, “INFLUENCE OF Momordica charantia (L.) ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF GLICLAZIDE IN ALLOXAN-INDUCED DIABETIC RATS,” Med. Sains J. Ilm. Kefarmasian, vol. 8, no. 3, pp. 1079–1088, 2023, doi: 10.37874/ms.v8i3.854.

[4] O. Zannou, H. Pashazadeh, M. Ghellam, A. Ali Redha, and I. Koca, “Enhanced ultrasonically assisted extraction of bitter melon (Momordica charantia) leaf phenolic compounds using choline chloride-acetic acid–based natural deep eutectic solvent: an optimization approach and in vitro digestion,” Biomass Convers. Biorefinery, vol. 14, no. 10, pp. 11491–11503, 2024, doi: 10.1007/s13399-022-03146-0.

[5] Z. Wang, S. Li, S. Ge, and S. Lin, “Review of Distribution, Extraction Methods, and Health Benefits of Bound Phenolics in Food Plants,” J. Agric. Food Chem., vol. 68, no. 11, pp. 3330–3343, 2020, doi: 10.1021/acs.jafc.9b06574.

[6] J. Liu, Y. Guo, J. Sun, Y. Lei, M. Guo, and L. Wang, “Extraction methods, multiple biological activities, and related mechanisms of Momordica charantia polysaccharide: A review,” Int. J. Biol. Macromol., vol. 263, no. P2, p. 130473, 2024, doi: 10.1016/j.ijbiomac.2024.130473.

[7] E. Quitério, C. Grosso, R. Ferraz, C. Delerue-Matos, and C. Soares, “A Critical Comparison of the Advanced Extraction Techniques Applied to Obtain Health-Promoting Compounds from Seaweeds,” Mar. Drugs, vol. 20, no. 11, pp. 1–40, 2022, doi: 10.3390/md20110677.

[8] T. Akmal, Y. P. Tanjung, A. I. Julianti, and A. G. Lestari, “Influence of extraction method on total phenolic content and antioxidant activity of Sappan Wood (Caesalpinia sappan L.) extract,” Sasambo J. Pharm., vol. 5, no. 2, pp. 55–62, 2024, doi: https://doi.org/10.29303/sjp.v5i2.364.

[9] T. Akmal, A. I. Julianti, Y. P. Tanjung, P. Mutiara, and S. Febriyanti, “Effect of extraction method on total phenolic content and antioxidant activity of Terminalia catappa ( L .) leaves The impact of technological advancements on human beings is not always,” PHARMASIPHA Pharm. J. Islam. Pharm., vol. 8, no. 2, pp. 1–11, 2024.

[10] L. Shen et al., “A comprehensive review of ultrasonic assisted extraction (UAE) for bioactive components: Principles, advantages, equipment, and combined technologies,” Ultrason. Sonochem., vol. 101, no. October, p. 106646, 2023, doi: 10.1016/j.ultsonch.2023.106646.

[11] K. Kumar, S. Srivastav, and V. S. Sharanagat, “Ultrasound assisted extraction (UAE) of bioactive compounds from fruit and vegetable processing by-products: A review,” Ultrason. Sonochem., vol. 70, no. July 2020, p. 105325, 2021, doi: 10.1016/j.ultsonch.2020.105325.

[12] Y. Xiang, Z. Liu, Y. Liu, B. Dong, C. Yang, and H. Li, “Ultrasound-assisted extraction, optimization, and purification of total flavonoids from Daphnegenkwa and analysis of their antioxidant, anti-inflammatory, and analgesic activities,” Ultrason. Sonochem., vol. 111, no. September, p. 107079, 2024, doi: 10.1016/j.ultsonch.2024.107079.

[13] A. Sanou et al., “Modelling and optimisation of ultrasound-assisted extraction of roselle phenolic compounds using the surface response method,” Sci. Rep., vol. 13, no. 1, pp. 1–9, 2023, doi: 10.1038/s41598-023-27434-5.

[14] I. A. Almusallam et al., “Optimization of ultrasound-assisted extraction of bioactive properties from date palm ( Phoenix dactylifera L .) spikelets using response surface methodology,” LWT, vol. 140, no. December 2020, p. 110816, 2021, doi: 10.1016/j.lwt.2020.110816.

[15] N. M. Hani, A. E. Torkamani, S. Zainul Abidin, W. A. K. Mahmood, and P. Juliano, “The effects of ultrasound assisted extraction on antioxidative activity of polyphenolics obtained from Momordica charantia fruit using response surface approach,” Food Biosci., vol. 17, pp. 7–16, 2017, doi: https://doi.org/10.1016/j.fbio.2016.11.002.

[16] J. J. Lee and K. Y. Yoon, “Optimization of ultrasound-assisted extraction of phenolic compounds from bitter melon (Momordica charantia) using response surface methodology,” CyTA - J. Food, vol. 19, no. 1, pp. 721–728, Jan. 2021, doi: 10.1080/19476337.2021.1973110.

[17] Y. Tao, Z. Zhang, and D.-W. Sun, “Kinetic modeling of ultrasound-assisted extraction of phenolic compounds from grape marc: Influence of acoustic energy density and temperature,” Ultrason. Sonochem., vol. 21, no. 4, pp. 1461–1469, 2014, doi: https://doi.org/10.1016/j.ultsonch.2014.01.029.

[18] Ó. Rodríguez, S. Bona, A. Stäbler, and L. Rodríguez-Turienzo, “Ultrasound-Assisted Extraction of Polyphenols from Olive Pomace: Scale Up from Laboratory to Pilot Scenario,” Processes, vol. 10, no. 12. p. 2481, 2022. doi: 10.3390/pr10122481.

[19] T. Akmal, A. I. Julianti, and S. S. Syamsudin, “Polyherbal Formulation Optimization From Clitoria Ternatea, Rosmarinus Officinalis and Aquilaria Malaccensis Using Simplex Lattice Design,” Int. J. Appl. Pharm., vol. 15, no. Special Issue 2, pp. 79–84, 2023, doi: 10.22159/ijap.2023.v15s2.15.

[20] F. Jasmin, A. Ika, J. Handayani, T. Akmal, B. Siliwangi, and P. Academy, “Optimization of Extraction Parameters for Phenolics and Flavonoids from Peony ( Paeonia lactiflora) Flowers Using Ultrasound-Assisted Extraction,” Hydrog. J. Kependidikan Kim., vol. 13, no. 1, pp. 1–11, 2025, doi: https://doi.org/10.33394/hjkk.v13i1.14346.

[21] D. Ananda, A. I. Julianti, and T. Akmal, “Optimization of Phenolic and Flavonoid Extraction in Lavandula Angustifolia using Ultrasonic Assistance Extraction,” Reka Buana J. Ilm. Tek. Sipil dan Tek. Kim., vol. 10, no. 1, pp. 25–36, 2025, doi: https://doi.org/10.33366/rekabuan a.v10i1.6608 keywords:

[22] L. M. Anaya-Esparza et al., “Design of Experiments for Optimizing Ultrasound-Assisted Extraction of Bioactive Compounds from Plant-Based Sources,” Molecules, vol. 28, no. 23. p. 7752, 2023. doi: 10.3390/molecules28237752.

[23] O. By-products, R. Quirantes-piné, and J. Lozano-sánchez, “Optimized Ultrasound-Assisted Extraction for Enhanced Recovery of Valuable Phenolic Compounds from,” Antioxidants, no. 14, p. 938, 2025, doi: https://doi.org/10.3390/ antiox14080938.

[24] A. A. Bin, A. Hamid, and K. Kerboua, “Ultrasonics Sonochemistry Ultrasonic-assisted extraction to enhance the recovery of bioactive phenolic compounds from Commiphora gileadensis leaves,” Ultrason. Sonochem., vol. 105, no. December 2023, p. 106852, 2024, doi: 10.1016/j.ultsonch.2024.106852.

[25] D. Hu, R. Xue, X. Zhuang, and X. Zhang, “Ultrasound-assisted extraction optimization of polyphenols from Boletus bicolor and evaluation of its antioxidant activity,” Front. Nutr., no. March, pp. 1–14, 2023, doi: 10.3389/fnut.2023.1135712.

[26] S. Sai-Ut, P. Kingwascharapong, M. A. Mazumder, and S. Rawdkuen, “Optimization of Ethanolic Extraction of Phenolic Antioxidants from Lychee and Longan Seeds Using Response Surface Methodology,” Foods, vol. 12, no. 15. p. 2827, 2023. doi: 10.3390/foods12152827.

[27] A. C. Andrade, F. T. Borsoi, A. S. Saliba, S. M. de Alencar, G. M. Pastore, and H. S. Arruda, “Optimization of Ultrasonic-Assisted Extraction of Phenolic Compounds and Antioxidant Activity from Araticum Peel Using Response Surface Methodology,” Plants, vol. 13, no. 18. p. 2560, 2024. doi: 10.3390/plants13182560.

[28] J. Pico, R. Y. Pismag, M. Laudouze, and M. M. Martinez, “Systematic evaluation of the Folin–Ciocalteu and Fast Blue BB reactions during the analysis of total phenolics in legumes, nuts and plant seeds,” Food Funct., vol. 11, no. 11, pp. 9868–9880, Nov. 2020, doi: 10.1039/d0fo01857k.

[29] I. L. Lawag, E. S. Nolden, A. A. M. Schaper, L. Y. Lim, and C. Locher, “A Modified Folin-Ciocalteu Assay for the Determination of Total Phenolics Content in Honey,” Applied Sciences, vol. 13, no. 4. p. 2135, 2023. doi: 10.3390/app13042135.

[30] S. Niglio, C. Razola-díaz, H. Waegeman, and V. Verardo, “Food grade pilot scale strategy for non-thermal extraction and recovery of phenolic compounds from orange peels,” LWT, vol. 205, no. June, p. 116538, 2024, doi: 10.1016/j.lwt.2024.116538.

[31] Y. Zhou and D. Lin, “Ultrasound-assisted optimized extraction and analysis of polysaccharides of Tricholoma matsutake,” no. September, pp. 1–11, 2024, doi: 10.3389/fsufs.2024.1433565.

Downloads

Published

2026-07-31

How to Cite

Statistical Modeling and Numerical Optimization of Ultrasound-Assisted Phenolic and Flavonoid Extraction from Momordica charantia Fruit. (2026). Journal of Tropical Pharmacy and Chemistry , 10(2), 64-72. https://doi.org/10.30872/jtpc.v10i2.430