Extraction of flavonoids from natural sources using modern techniques: A review

Mediterranean Journal of www.mmj.org.ly Medicine & Medical Sciences Mediterr J Med Med Sci Baskaran et al. Mediterr J Med Med Sci. 2025; 1(3): 43-46. Page 43 MINI-REVIEW article Extraction of flavonoids from natural sources using modern techniques: A review Karthiraja A S * , Kowsalya K Durga Sri R , Revathi S , and Karthika A Department of Pharmaceutical Analysis, The Erode College of Pharmacy and Research Institute, Erode-638112, Tamil Nadu, India * Author to whom correspondence should be addressed Article number: 16, Received: 10-11-2025, Accepted: 26-11-2025, Published online: 28-11-2025 HOW TO CITE THIS Karthiraja et al. Extraction of flavonoids from natural sources using modern techniques: A review. Mediterr J Med Med Sci. 2025; 1(3): 43-46. [Article number: 16]. https://doi.org/10.5281/zenodo.17738965 Keywords: Bioactive compounds, flavonoids extraction, green extraction techniques Abstract: Flavonoids, a major class of bioactive polyphenols present in plants, exhibit antioxidant, antiinflammatory, and antimicrobial properties. Their extraction plays a crucial role in the pharmaceutical, nutraceutical, and food industries. Traditional extraction methods, such as prolonged solvent-based techniques involving elevated temperatures, often suffer from inefficiency and compound degradation. Modern extraction technologies, including microwave-assisted extraction, ultrasound-assisted extraction, pressurized liquid extraction, and supercritical fluid extraction, offer improved efficiency, reduced solvent consumption, and enhanced preservation of bioactive integrity. This review focuses on these advanced methods, highlighting operational parameters, advantages, limitations, and recent improvements, with an emphasize on green and sustainable extraction. Introduction Flavonoids, a major class of bioactive polyphenols present in plants, and widely distributed secondary metabolites contributing to plant defense and human health. They exhibit antioxidant, anti-inflammatory, and antimicrobial properties. Flavonoids are structural derivatives that were formed from the phenyl-propanoid pathway, and that exhibit diversity in structure and bioavailability of these compounds [1]. Their extraction plays a crucial role in the pharmaceutical, nutraceutical, and food industries [2, 3]. Efficient extraction techniques are essential to maximize yield, shorten processing time, and minimize environmental impact [4]. such as prolonged solvent-based techniques involving elevated temperatures, often suffer from inefficiency and compound degradation [5]. Conventional extraction processes such as maceration and Soxhlet extraction are simple but solvent-intensive, slow, and prone to degradation of thermolabile compounds [6]. Modern techniques overcome these drawbacks by using physical intensification methods or eco-friendly solvents that enhance extraction kinetics and selectivity [7]. Modern extraction technologies, including microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), pressurized liquid extraction (PLE), and supercritical fluid extraction (SFE), provide improved efficiency [8], reduced solvent consumption, and enhanced preservation of bioactive integrity [9-12]. This review focuses on these advanced methods, highlighting operational parameters, advantages, limitations, and recent improvements emphasizing green and sustainable extraction [13]. Copyright© 2025. This open-access article is distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Mediterranean Journal of www.mmj.org.ly Medicine & Medical Sciences Mediterr J Med Med Sci Baskaran et al. Mediterr J Med Med Sci. 2025; 1(3): 43-46. Page 44 Conventional extraction techniques Maceration and percolation maceration and percolation involve prolonged soaking or solvent flow through plant matrices at ambient temperature using solvents such as water, ethanol, or methanol. These methods are simple and suitable for heat-sensitive compounds but require long processing times, high solvent usage, and risk degradation from extended exposure [14]. Soxhlet extraction Soxhlet extraction uses continuous solvent reflux to ensure efficient extraction, but prolonged heating can degrade thermolabile flavonoids, and the process is solventand energy-intensive [2]. Modern extraction techniques Microwave-assisted extraction (MAE): Microwave energy rapidly heats solvents and plant tissues, enhancing mass transfer through dipole rotation and ionic conduction. This accelerates extraction (minutes instead of hours) while reducing solvent use. Excessive exposure, however, can degrade sensitive compounds, and specialized equipment is required. Ultrasound-assisted extraction (UAE) Ultrasonication induces cavitation that disrupts cell walls, improving solvent penetration. It is energy-efficient, scalable, and environmentally friendly but demands optimization of frequency and duration to prevent compound degradation. Pressurized liquid extraction (PLE)/accelerated solvent extraction (ASE): PLE utilizes elevated temperature and pressure to maintain solvents in a liquid state above their boiling point, enhancing solubility and diffusion. This delivers high extraction efficiency and reduced processing time. Careful parameter optimization is needed to avoid thermal decomposition. Supercritical fluid extraction (SFE): SFE employs supercritical CO₂ as a solvent, combining liquid-like solvating power with gas-like diffusivity. It is highly selective, leaves no solvent residues, and preserves thermolabile compounds. For polar flavonoids, modifiers such as ethanol are often needed [15]. Enzyme-assisted extraction (EAE) Cellulases and pectinases hydrolyze plant cell walls, releasing flavonoids under mild and eco-friendly conditions. This biological approach enhances yield but can be costly and time-intensive. Electric field-assisted extraction (pulsed electric field, PEF): PEF uses short, high-voltage impulses to permeabilize cell membranes, accelerating mass transfer while retaining compound stability. It is non-thermal and rapid but requires careful equipment calibration for scalability. Examples of flavonoid extraction from plants: Camellia sinensis (Tea): Extraction with 70.0% ethanol under reflux (90°C, 6.0 hrs.) yields catechins; optimized MAE conditions: 60°C, 70.0% ethanol, 80 min, 1: 20 ratios. Ginkgo biloba: Enzyme pretreatment with cellulase and pectinase prior to ethanol extraction enhances flavonoid yield. Citrus species: Sequential Soxhlet extraction using chloroform, ethyl acetate, and methanol concentrates flavonoids in polar fractions. Glycyrrhiza glabra (Licorice): Methanol or ethanol extraction, improved with ultrasonic-cold plasma methods for glycyrrhizic acid. Scutellaria baicalensis (Chinese Skullcap): Ultrasonic extraction using 53.0% ethanol yields baicalin-rich extracts with conditions optimized at 62°C for 2.0 hrs. Sophora japonica: Water reflux followed by resin purification produces rutin and kaempferol; UAE significantly improves yields. Vitis vinifera (Grapes): Extraction with ethanol or water under ambient or ASE conditions recovers flavanols effectively. Allium cepa (Onion): MAE with 62.0% methanol at 56°C for two minutes optimizes anthocyanin recovery; UAE isolates quercetin efficiently. Silybum marianum (Milk Thistle): Ultrasound extraction in ethanol yields high-purity silymarin. Trifolium pratense (Red Clover): Reflux or ultrasound extraction using ethanol-water mixtures effectively isolates isoflavones. Mediterranean Journal of www.mmj.org.ly Medicine & Medical Sciences Mediterr J Med Med Sci Baskaran et al. Mediterr J Med Med Sci. 2025; 1(3): 43-46. Page 45 Conclusion: Modern extraction methods significantly improve efficiency, sustainability, and preservation of bioactive compounds compared to conventional processes. Continued research focuses on hybrid extraction systems, response surface methodology for optimization, and the development of natural deep eutectic solvents (NADES) and ionic liquids for green extraction. Industrial-scale adaptation of these greener and more efficient methods will be important for cost-effective and eco-friendly flavonoid production. References 1. Nizamuddin SFS. Polyphenol-rich black chokeberry (Aronia melanocarpa) and its therapeutic potential in type 2 diabetes mellitus: A comprehensive review. Mediterranean Journal of Medicine and Medical Sciences. 2025; 1(3): 31-42. doi: 10.5281/zenodo.17619107 2. Chaves JO, de Souza MC, da Silva LC, Lachos-Perez D, Torres-Mayanga PC, Machado APDF, et al. Extraction of flavonoids from natural sources using modern techniques. Frontiers in Chemistry. 2020; 8: 507887. doi: 10.3389/ fchem.2020.507887 3. Bitwell C, Indra SS, Luke C, Kakoma MK. A review of modern and conventional extraction techniques and their applications for extracting phytochemicals from plants. Scientific African. 2023; 19: e01585. doi: 10.1016/j.sciaf. 2023.e01585 4. Rodríguez De Luna SL, Ramírez-Garza RE, Serna Saldívar SO. Environmentally friendly methods for flavonoid extraction from plant material: Impact of their operating conditions on yield and antioxidant properties. Scientific World Journal. 2020; 2020: 6792069. doi: 10.1155/2020/6792069 5. Farooq U, Nadeem L, Nangdev P, Mahmood T, Moqaddas A. Green approach to novel flavonoid extraction: Purification methods and therapeutic benefits for optimizing health and wellness initiatives. Journal of Health and Rehabilitation Research. 2024; 4(1): 1701-1705. doi: 10.61919/jhrr.v4i1.701 6. Astyka R. Optimization of microwave-assisted extraction of total flavonoids. Journal of Applied Pharmaceutical Science. 2024; 14(8): 150-159. doi: 10.7324/JAPS.2024.170411 7. Parwata A, Manuaba P, Yasa S. The potency of flavonoid compounds in water extract Gyrinops versteegii leaves as natural antioxidants sources. Biomedical and Pharmacology Journal. 218; 11(3): 1501-1511. doi: 10.13005/bpj/ 1517 8. Han Z, Li C, Liu G. Recent advances in the extraction, purification and analytical techniques for flavonoids from plants: Taken hawthorn as an example. Journal of Food Composition and Analysis. 2025; 141: 107372. doi: 10.1016/j.jfca.2025.107372 9. Shi L, Wu Y-Y, Zhu Y-T, Yu T-S, Zhou Y, Xie M-D, Pang H-Q. The rise of green solvents: Application and efficiency of deep eutectic solvents in the extraction of flavonoids. Journal of Food Science. 2025; 90(7): 1-14. doi: 10.1111/1750-3841.70381 10. Chen X-Q, Li Z-H, Liu L-L, Wang H, Yang S-H, Zhang J-S, Zhang Y. Green extraction using deep eutectic solvents and antioxidant activities of flavonoids from two fruits of Rubia species. LWT Food Science and Technology. 2021; 148; 111708. doi. 10.1016/j.lwt.2021.111708 11. Wang R, Li W, Fang C, Zheng X, Liu C, Huang Q. Extraction and identification of new flavonoid compounds in dandelion Taraxacum mongolicum Hand.-Mazz. with evaluation of antioxidant activities. Scientific Reports. 2023; 13: 2166. doi: 10.1038/s41598-023-28775-x 12. Alshintari ME, Bonner PLR, Hargreaves AJ. Effect of dietary flavonoids on amine incorporation activity of transglutaminase 2 enzyme. Mediterranean Journal of Pharmacy and Pharmaceutical Sciences. 2023; 3(1): 64-69. doi: 10.5281/zenodo.7771704 13. Munayr MS, Alshreef ZAB. Phytochemical characterization and radical-scavenging activity of solvent fractions from corn silk. Mediterranean Journal of Pharmacy and Pharmaceutical Sciences. 2025; 5(3): 83-93. doi: 10.5281/ zenodo.17094971 14. Ojha S, Raj A, Roy A, Roy. Extraction of total phenolics, flavonoids, and tannins from Paederia foetida L. leaves and their relation with antioxidant activity. Pharmacognosy Journal. 2018; 10(3): 541-547. doi: 10.5530/pj.2018. 3.88 15. Vinitha UG, Sathasivam R, Muthuraman MS, Park SU. Intensification of supercritical fluid extraction of flavonoids: A comprehensive review. Physiological and Molecular Plant Physiology. 2022; 118: 101815. doi: 10.1016/j.pmpp.2022.101815 Mediterranean Journal of www.mmj.org.ly Medicine & Medical Sciences Mediterr J Med Med Sci Baskaran et al. Mediterr J Med Med Sci. 2025; 1(3): 43-46. Page 46 Author contribution: KAS & RS conceived and designed the study. KAS, KK, RS & KA collected data. KAS, DSR & RS contributed to data analysis. KAS, KK & KA drafted the manuscript/revised it for important intellectual context. All the authors approved the final version of the manuscript and agreed to be accountable for its contents. Conflict of interest: The authors declare the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethical issues: The authors completely observed ethical issues, including plagiarism, informed consent, data fabrication or falsification, and double publication or submission. Generative AI disclosure: No generative AI was used in the preparation of this manuscript.