Journals / Hacettepe Journal of Biology and Chemistry / 2026 / Volume: 53 Issue: 2

Modern Approaches to the Separation and Purification of Natural Products

Doğal Ürünlerin Ayırma ve Saflaştırma İçin Modern Yaklaşımlar

Çiğdem Bilgi(İSTANBUL ÜNİVERSİTESİ-CERRAHPAŞA)0000-0003-1150-7061
Nilay Karahan(EGE ÜNİVERSİTESİ, ECZACILIK FAKÜLTESİ)0009-0001-9319-9586
Pages
—
Publication Date
2025-04-01
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

This review explores modern approaches to separating and purifying natural products and their advantages over traditional methods.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Natural products are bioactive compounds derived from plants, animals, and microorganisms, holding great importance in medicine and pharmacy.
📊
Key Findings & Data:Today, the term 'natural product’ generally refers to secondary metabolites from plants with various biological activities.
💡
Conclusion & Impact:This review explores modern approaches to separating and purifying natural products and their advantages over traditional methods.
🔬Design:Review & Systematic Survey
📍Scope:Comprehensive Sample
⚙️Variables:Bioactive compound · chromatography · spectroscopy

Abstract

Natural products are bioactive compounds derived from plants, animals, and microorganisms, holding great importance in medicine and pharmacy. Today, the term 'natural product’ generally refers to secondary metabolites from plants with various biological activities. These products have addressed primary health issues for thousands of years and continue to treat many diseases. Given the low levels of bioactive substances in plants and the difficulty of isolating these molecules in high purity, the importance of separating and purifying natural products becomes evident. Traditional methods of isolation and purification are expensive, time-consuming, and labor-intensive. However, advancements in science and technology have led to new approaches that are fast, effective, low-cost, and highly applicable. These modern methods enable the isolation of substances, determination of their bioactivity, and allow for the monitoring of their interactions, potential synergistic effects, and toxicities. These methods also help reduce cost and effort and save time, which is crucial for academia and the pharmaceutical industry. Numerous studies highlight drug-like molecules discovered through these new approaches. This review explores modern approaches to separating and purifying natural products and their advantages over traditional methods.

Özet

Doğal ürünler, bitkiler, hayvanlar ve mikroorganizmalardan elde edilen, tıp ve eczacılık alanında büyük öneme sahip biyoaktif bileşiklerdir. Günümüzde "doğal ürün" terimi genellikle bitkilerden elde edilen ve çeşitli biyolojik aktivitelere sahip sekonder metabolitleri ifade etmektedir. Bu ürünler binlerce yıldır temel sağlık sorunlarına çözüm olmuştur ve halen birçok hastalığın tedavisinde kullanılmaya devam etmektedir. Bitkilerdeki biyoaktif maddelerin düşük seviyelerde bulunması ve bu moleküllerin yüksek saflıkta izole edilmesinin zorluğu, doğal ürünlerin ayrıştırılması ve saflaştırılmasının önemini ortaya koymaktadır. Geleneksel izolasyon ve saflaştırma yöntemleri pahalı, zaman alıcı ve yoğun emek gerektiren yöntemlerdir. Ancak bilim ve teknolojindeki ilerlemeler, hızlı, etkili, düşük maliyetli ve yüksek uygulanabilirliğe sahip yeni yaklaşımların ortaya çıkmasına yol açmıştır. Bu modern yöntemler sayesinde maddelerin izolasyonu, biyoaktivitelerinin belirlenmesi, etkileşimlerinin, potansiyel sinerjik etkilerinin ve toksisitelerinin izlenmesi mümkün hale gelmiştir. Ayrıca bu yöntemler maliyeti azaltmaya ve zaman tasarrufu sağlamaya yardımcı olur ki bu da akademi ve ilaç endüstrisi için oldukça önemlidir. Çok sayıda çalışma, bu yeni yaklaşımlar sayesinde keşfedilen ilaç benzeri molekülleri vurgulamaktadır. Bu derleme, doğal ürünlerin ayrıştırılması ve saflaştırılmasında kullanılan modern yaklaşımları ve geleneksel yöntemlere göre avantajlarını incelemektedir.

🔖

Cite This Article

Bilgi, Ç., Karahan, N. (2025). Modern Approaches to the Separation and Purification of Natural Products. Hacettepe Journal of Biology and Chemistry, Volume: 53 Issue: 2. https://doi.org/10.15671/hjbc.1527647

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (58)

  1. D.D. Baker, M. Chu, U. Oza, V. Rajgarhia, The value of natural products to future pharmaceutical discovery, Nat. Prod. Rep., 24:6 (2007) 1225-1255, 2007.
  2. O. Sticher, Natural product isolation, Nat. Prod. Rep., 25:3 (2008) 517-554.
  3. Q.W. Zhang, L.G. Lin, W.C. Ye, Techniques for extraction and isolation of natural products: a comprehensive review, Chin. Med., 13:1 (2018) 26.
  4. A. G. Atanasov, B.Waltenberger, E-M. Pferschy-Wenzig, T. Linder, C. Wawrosch, P. Uhrin, V. Temml, L. Wang, S. Schwaiger, E.H. Heiss, J.M. Rollinger, D. Schuster, J.M. Breuss, V. Bochkov, M.D. Mihovilovic, B. Kopp, R. Bauer, V.M. Dirsch, H. Stuppner, Discovery and resupply of pharmacologically active plant-derived natural products: A review, Biotechnol. Adv., 33:8 (2015) 1582–1614.
  5. S. Bernardini, A. Tiezzi, V. Laghezza Masci, E. Ovidi, Natural products for human health: an historical overview of the drug discovery approaches, Nat. Prod. Res., 32:16 (2018) 1926–1950.
  6. J. S. Zarins-Tutt, T.T. Barberi, H. Gao, A. Mearns-Spragg, L. Zhang, D.J. Newman, R.J.M. Goss, Prospecting for new bacterial metabolites: a glossary of approaches for inducing, activating and upregulating the biosynthesis of bacterial cryptic or silent natural products, Nat. Prod. Rep. 33:1 (2016) 54–72.
  7. J. Wiese, B. Ohlendorf, M. Blümel, R. Schmaljohann, J. F. Imhoff, Phylogenetic Identification of Fungi Isolated from the Marine Sponge Tethya aurantium and Identification of Their Secondary Metabolites, Mar. Drugs, 9:4 (2011) 561–585.
  8. G. Atanasov, S. B. Zotchev, V. M. Dirsch, C. T. Supuran, “Natural products in drug discovery: advances and opportunities,” Nat Rev Drug Discov, vol. 20, no. 3, pp. 200–216.
  9. K. Scherlach, C. Hertweck, Triggering cryptic natural product biosynthesis in microorganisms, Org. Biomol. Chem., 7:9 (2009) 1753.
  10. Z. Wasil, K.A.K. Pahirulzaman, C. Butts, T.J. Simpson, C.M. Lazarus, R.J. Cox, One pathway, many compounds: heterologous expression of a fungal biosynthetic pathway reveals its intrinsic potential for diversity, Chem. Sci., 4:10 (2013) 3845.
  11. R. Pan, X. Bai, J. Chen, H. Zhang, H. Wang, Exploring Structural Diversity of Microbe Secondary Metabolites Using OSMAC Strategy: A Literature Review, Front. Microbiol., 10 (2019), doi: 10.3389/fmicb.2019.00294.
  12. D. M. Selegato, I. Castro-Gamboa, Enhancing chemical and biological diversity by co-cultivation, Front. Microbiol., 14 (2023) 1117559.
  13. V. Yoon, J.R. Nodwell, Activating secondary metabolism with stress and chemicals, J. Ind. Microbiol. Biotechnol., 41:2 (2014) 415–424.
  14. H.B. Bode, B. Bethe, R. Höfs, A. Zeeck, Big Effects from Small Changes: Possible Ways to Explore Nature’s Chemical Diversity, ChemBioChem., 3:7 (2002) 619.
  15. K.P. Mishra, L. Ganju, M. Sairam, P.K. Banerjee, R.C. Sawhney, A review of high throughput technology for the screening of natural products, Biomedicine & Pharmacotherapy, 62:2 (2008) 94–98.
  16. J.A. Landro, I.C.A. Taylor, W.G. Stirtan, D.G. Osterman, J. Kristie, E.J. Hunnicutt, P.M.M. Rae, P.M. Sweetnam, HTS in the new millennium, J. Pharmacol. Toxicol. Methods, 44:1 (2000) 273–289.
  17. J. Hughes, S. Rees, S. Kalindjian, K. Philpott, Principles of early drug discovery, Br. J. Pharmacol., 162:6 (2011).
  18. S. Fox, S. Farr-Jones, L. Sopchak, A. Boggs, H.W. Nicely, R. Khoury, M. Biros, High-Throughput Screening: Update on Practices and Success, SLAS Discovery, 11:7 (2006) 864–869.
  19. C.A. Lipinski, F. Lombardo, B.W. Dominy, P.J. Feeney, Experimental and computational approaches to estimate solubility and permeability in drug discovery and development, Adv. Drug. Deliv. Rev., 46 (2001) 1–3.
  20. V. Blay, B. Tolani, S.P. Ho, M.R. Arkin, High-throughput screening: today’s biochemical and cell-based approaches, Drug. Discov. Today, 25:10 (2020) 1807–1821.
  21. O. Osakwe, The Significance of Discovery Screening and Structure Optimization Studies, Social Aspects of Drug Discovery, Development and Commercialization, (2016) 109–128.
  22. P. Szymański, M. Markowicz, E. Mikiciuk-Olasik, Adaptation of High-Throughput Screening in Drug Discovery—Toxicological Screening Tests, Int. J. Mol. Sci., 13:1 (2011) 427–452.
  23. S. N. R. Gajula, N. Nadimpalli, and R. Sonti, “Drug metabolic stability in early drug discovery to develop potential lead compounds,” Drug Metab Rev, vol. 53, no. 3, pp. 459–477, 2021.
  24. S.H. Bal, F. Budak, Genomik, Proteomik Kavramlarına Genel Bakış ve Uygulama Alanları, Uludağ Üniversitesi Tıp Fakültesi Dergisi, 39:1 (2013) 65–69.
  25. Ş. Ö.Budak, S. Dönmez, Gıda Biliminde Yeni Omik Teknolojileri, The Journal of Food, 37:3 (2012) 173–179.
  26. M.J. Aardema, J.T. MacGregor, Toxicology and genetic toxicology in the new era of ‘toxicogenomics’: impact of ‘-omics’ technologies, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 499:1 (2002) 13–25.
  27. K. Wanichthanarak, J.F. Fahrmann, D. Grapov, Genomic, Proteomic, and Metabolomic Data Integration Strategies, Biomark Insights, 10:4 (2015) 29511.
  28. B.S. Yarman, H. Gürkan, Ü. Güz, B. Aygün, A New Modelling Method of the ECG Signals Based on the use of an Optimized Predefined Functional Database, Acta. Cardiol, 58:3 (2003) 59–61.
  29. P.A. Hohenlohe, W.C. Funk, O.P. Rajora, Population genomics for wildlife conservation and management, Mol. Ecol., 30:1 (2021) 62–82.
  30. Ö. Gök, A. Aslan, O. Erman, İnsan ENCODE, HapMap ve 1000 Genom Projeler, Erciyes University Journal of Natural and Applied Sciences, 33:2 (2017) 35–42.
  31. W.S. Bush, J.H. Moore, Chapter 11: Genome-Wide Association Studies, PLoS Comput Biol, 8:12 (2012) 1002822.
  32. L. Cocolin, K. Rantsiou, Molecular Biology | Transcriptomics, Encyclopedia of Food Microbiology, Elsevier, Netherlands, 2014.
  33. K.H. Liang, Transcriptomics. Bioinformatics for Biomedical Science and Clinical Applications, Elsevier, Netherlands, 2013.
  34. M. Sarıman, S.S. Ekmekci, N. Abacı, A. Çakiris, F. Paçal, Z. Emrence, D. Üstek, Transcriptome Analysis Using Next Generation Sequencing, Experimed., 10:4 (2015) 51–59.
  35. A. Subramanian, P. Tamayo, V.K. Mootha, S. Mukherjee, B.L. Ebert, M.A. Gilette, A. Paulovic, S.L. Pomeroy, T.R. Golub, E.S. Lander, J.P. Mesirov Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles, Proceedings of the National Academy of Sciences, 102: 43 (2005) 15545–15550.
  36. Z. Miao, B.D. Humphreys, A.P. McMahon, J. Kim, Multi-omics integration in the age of million single-cell data, Nat. Rev. Nephrol., 17:11 (2021) 710–724.
  37. G. Marko-Varga, Proteomics principles and challenges, Pure and Applied Chemistry, 76:4 (2004) 829–837.
  38. E.Başaran, S. Aras, General Outlook and Applications of Genomics, Proteomics and Metabolomics, Turkish Bulletin of Hygiene and Experimental Biology, 67:2 (2010) 85–96.
  39. H. Kasap, P. Pazarcı, Sistem Biyolojisi, Arşiv,19:25 (2010) 25–35.
  40. C. B. Kasurka, Moleküler Toksikoloji ve ‘Omik’ Teknolojileri, Nevşehir Bilim ve Teknoloji Dergisi, 8:1 (2019) 42–55.
  41. M. Moreira, D. Schrama, A.P. Farinha, M. Cerqueira, Fish pathology research and diagnosis in aquaculture of farmed fish; a proteomics perspective, Animals, 11:1 (2021) 125.
  42. J.C. Venter, A Part of the Human Genome Sequence, Science, 299:5610 (2003) 1183–1184.
  43. R. Goodacre, Metabolomics – the way forward, Metabolomics, 1:1 (2005) 1–2, doi: 10.1007/s11306-005-1111-7.
  44. Q. Zhao, J.L. Zhang, and F. Li, Application of Metabolomics in the Study of Natural Products, Nat. Prod. Bioprospect, 8:4 (2018) 321–334.
  45. L. Harvey, R. Edrada-Ebel, R.J. Quinn, The re-emergence of natural products for drug discovery in the genomics era, Nat. Rev. Drug Discov., 14:2 (2015) 111–129.
  46. Y. Gao, Y. Wang, H. Chung, K. Chen, T. Shen, C. Hsu, Molecular networking as a dereplication strategy for monitoring metabolites of natural product treated cancer cells, Rapid Communications in Mass Spectrometry, 34:S1 (2020).
  47. F. Vincenti, C. Montesano, F. Di Ottavio, A. Gregory, D. Compagnone, M. Sergi, P. Dorrestein, Molecular networking: a useful tool for the identification of new psychoactive substances in seizures by LC–HRMS, Front. Chem., 8 (2020) 572952.
  48. E. Fox Ramos, L. Evanno, E. Poupon, P. Champy, M.A. Beniddir, Natural products targeting strategies involving molecular networking: different manners, one goal, Nat. Prod. Rep., 36:7 (2019) 960–980.
  49. S. Allard, P. Allard, I. Morel, T. Gicquel, Application of a molecular networking approach for clinical and forensic toxicology exemplified in three cases involving 3‐MeO‐PCP, doxylamine, and chlormequat, Drug. Test. Anal., 11:5 (2019) 669–677.
  50. J. Hubert, J.M. Nuzillard, J.H. Renault, Dereplication strategies in natural product research: How many tools and methodologies behind the same concept?, Phytochemistry Reviews,16:1 (2017) 55–95, doi: 10.1007/s11101-015-9448-7.
  51. D.D. Nguyen, C.H. Wu, W.J. Moree, A. Lamsa, M.H. Medema, X. Zhao, R.G. Gavilan, M. Aparicio et al., MS/MS networking guided analysis of molecule and gene cluster families, Proceedings of the National Academy of Sciences, 110:28 (2013).
  52. R.A. Quinn, L.F. Nothias, O. Vining, M. Meehan, E. Esquenazi, P.C. Dorrestein, Molecular Networking As a Drug Discovery, Drug Metabolism, and Precision Medicine Strategy, Trends Pharmacol Sci, 38: 2 (2017) 143–154.
  53. A. C. Pilon, H. Gu, D. Raftery, V.S. Bolzani, N.P. Lopes, I. Castro-Gamboa, F. Carnevale Neto, Mass Spectral Similarity Networking and Gas-Phase Fragmentation Reactions in the Structural Analysis of Flavonoid Glycoconjugates, Anal Chem, 91:16 (2019) 10413–10423.
  54. S. Woo, K. Bin Kang, J. Kim, S.H. Sung, Molecular Networking Reveals the Chemical Diversity of Selaginellin Derivatives, Natural Phosphodiesterase-4 Inhibitors from Selaginella tamariscina, J. Nat. Prod, 82:7 (2019) 1820–1830.
  55. N. Garg, C.A. Kapono, Y.W. Lim, N. Koyama, M.J.A. Vermeij, D. Conrad, F. Rohwer, P.C. Dorrestein, Mass spectral similarity for untargeted metabolomics data analysis of complex mixtures, Int. J. Mass. Spectrom., 377 (2015) 719–727.
  56. M. Wang, J.J. Carver, V.V. Phelan, L.M. Sanchez, N. Garg, Y. Peng, D.D. Nguyen, J. Watrous et al., Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking, Nat. Biotechnol, 34:8 (2016) 828–837.
  57. P. Shannon, A. Markiel, O. Ozier, N.S. Baliga, J.T. Wang, D. Ramage, N. Amin, B. Schwikowski, Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks, Genome Res., 13:11 (2003) 2498–2504.
  58. E.Başaran, S. Aras, General Outlook and Applications of Genomics, Proteomics and Metabolomics, Turkish Bulletin of Hygiene and Experimental Biology, 67:2 (2010) 85–96.