İklim Kaynaklı Bitkisel Sekonder Metabolit Değişimleri: Tıbbi Kalite, Standardizasyon ve Terapötik Etkinlik Üzerine Etkileri

Year 2026, Volume: 11 Issue: 1 , 44 - 54 , 30.04.2026

Ufuk Kuşkun

https://doi.org/10.25279/sak.1895917

https://izlik.org/JA43GL22EA

Abstract

Arka Plan: Sekonder metabolitler, milyonlarca yıllık bitki evrimi boyunca savunma, iletişim ve çevresel adaptasyon süreçlerini düzenlemek üzere ortaya çıkmış temel biyokimyasal ürünlerdir. Terpenoidler, fenolikler, alkaloidler ve poliketidler gibi bu bileşikler tarihsel olarak bitki–mikroorganizma ve bitki–herbivor etkileşimlerini şekillendirmiş; aynı zamanda insanlar için önemli farmakolojik özellikler kazanmıştır. Bununla birlikte günümüzde artan sıcaklıklar, yükselen atmosferik CO₂ düzeyleri, artmış UV-B radyasyonu ve giderek şiddetlenen kuraklık stresleri gibi küresel iklim dinamikleri, bu metabolitlerin biyosentezi, birikimi ve işlevsel çeşitlenmesi üzerinde kritik zorluklar ve fırsatlar yaratmaktadır.
Amaç: Bu derleme, bitkisel sekonder metabolizmanın tarihsel evrimsel geçişlerini sentezleyerek, güncel iklim değişikliğinin biyosentetik yolaklar ve tıbbi öneme sahip türlerdeki fitokimyasal profiller üzerindeki etkilerini mekanistik bir çerçevede değerlendirmeyi amaçlamaktadır.
Yöntem: 2015–2025 yılları arasında yayımlanan çalışmaları kapsayacak şekilde PubMed, Web of Science ve Scopus veri tabanlarında kapsamlı bir literatür taraması yapılmış; özellikle iklim kaynaklı biyokimyasal modülasyonları inceleyen deneysel çalışmalar, çoklu-omik yaklaşımlar ve metabolomik analizler önceliklendirilmiştir.
Bulgular: Bulgular, yükseltilmiş CO₂ düzeylerinin karbon akışını şikimat yoluna yönlendirerek fenolik ve flavonoid gibi karbon bazlı metabolitlerde artışa yol açtığını göstermektedir. Buna karşılık ısı stresi ve kuraklık, MYB, bHLH, WRKY ve NAC gibi transkripsiyon faktörlerinin ROS aracılı aktivasyonu yoluyla terpenoid ve alkaloid biyosentezinin belirgin şekilde artmasıyla ilişkilidir. Artmış UV-B maruziyeti, fotoprotektif bir uyum mekanizması olarak flavonoid birikimini sürekli biçimde teşvik etmektedir. Tür düzeyindeki analizler; Artemisia annua’da artemisinin, Tanacetum parthenium’da parthenolide, Ferula türlerinde seskiterpen laktonlar ve Mentha türlerinde uçucu yağ bileşenlerinde belirgin kaymalar olduğunu ortaya koymaktadır. Bu değişimlerin tamamı, tıbbi bitkilerden elde edilen terapötik ürünlerin farmakolojik etkinliği, standardizasyonu ve kalite kontrolü açısından doğrudan sonuçlar taşımaktadır.
Sonuç: Sekonder metabolit biyosentezi, doğası gereği dinamik olup küresel iklim parametrelerine yüksek duyarlılık göstermektedir. İklim–metabolit etkileşimlerinin moleküler, biyokimyasal ve ekolojik düzeylerde anlaşılması; fitokimyasal çeşitliliğin korunması, farmasötik standardizasyonun sağlanması ve iklim dayanıklı tıbbi bitki kaynaklarının geliştirilmesi açısından kritik önemdedir. Kontrollü ortam tarımı, genom düzenleme teknolojileri ve iklim–metabolit etkileşimine yönelik öngörücü modellerin entegrasyonu, hızlanan küresel iklim değişikliği koşullarında biyoaktif bileşik üretiminin sürdürülebilirliğini güvence altına almak için umut verici stratejiler sunmaktadır.

Keywords

Sekonder metabolitler , İklim değişikliği , Fitokimyasal standardizasyon , Tıbbi bitkiler , Abiyotik stres

Climate-Driven Modulation of Plant Secondary Metabolites: Implications for Medicinal Quality, Standardization, and Therapeutic Efficacy

https://izlik.org/JA43GL22EA

Abstract

Background: Secondary metabolites are essential biochemical products that have emerged through millions of years of plant evolution to mediate defense, communication, and environmental adaptation. Historically, these compounds—such as terpenoids, phenolics, alkaloids, and polyketides—have shaped plant–microbe and plant–herbivore interactions, while simultaneously acquiring substantial pharmacological relevance for humans. However, current global climate dynamics, including rising temperatures, elevated atmospheric CO₂, increased UV-B radiation, and progressive drought stress, pose critical challenges and opportunities for the biosynthesis, accumulation, and functional diversification of these metabolites.
Aim: This narrative review synthesizes historical evolutionary transitions in plant secondary metabolism and provides an updated, mechanistic evaluation of how contemporary climate change alters biosynthetic pathways and phytochemical profiles across medicinally important species.
Methods: A comprehensive literature search was performed using PubMed, Web of Science, and Scopus for studies published between 2015 and 2025, with emphasis on experimental, multi-omics, and metabolomics-based approaches evaluating climate-driven biochemical modulation in plants.
Results: Evidence indicates that elevated CO₂ concentrations tend to enhance carbon-based metabolites, particularly phenolics and flavonoids, by redirecting carbon flux toward the shikimate pathway. Conversely, heat stress and drought are strongly associated with upregulation of terpenoid and alkaloid biosynthesis through ROS-mediated activation of transcription factors such as MYB, bHLH, WRKY, and NAC. Increased UV-B exposure consistently promotes flavonoid accumulation as a photoprotective mechanism. Species-specific analyses reveal significant shifts in key metabolites: artemisinin in Artemisia annua, parthenolide in Tanacetum parthenium, sesquiterpene lactones in Ferula spp., and essential oil constituents in Mentha species. Collectively, these alterations hold direct consequences for pharmacological potency, standardization, and quality control of plant-derived therapeutics.
Conclusion: Secondary metabolite biosynthesis is intrinsically dynamic and highly sensitive to global climate parameters. Understanding climate–metabolite interactions at molecular, biochemical, and ecological levels is crucial for preserving phytochemical diversity, ensuring pharmaceutical standardization, and developing climate-resilient medicinal plant resources. Future strategies integrating controlled-environment agriculture, genome editing, and predictive climate–metabolite modelling may offer sustainable solutions to secure bioactive compound production under accelerating global climate change.

Keywords

Secondary metabolites , Climate change , Phytochemical standardization , Medicinal plants , Abiotic stress

References

• A, H. W.-F. A. & C. P., & 2011, undefined. (2011). Plants containing pyrrolizidine alkaloids: toxicity and problems. Taylor & FrancisH WiedenfeldFood Additives & Contaminants: Part A, 2011•Taylor & Francis, 28(3), 282–292. https://doi.org/10.1080/19440049.2010.541288
• Agati, G., & Tattini, M. (2010). Multiple functional roles of flavonoids in photoprotection. JSTORG Agati, M TattiniThe New Phytologist, 2010•JSTOR, 186(4), 786–793. https://doi.org/10.1111/j.1469-8137.2010.03269.x
• Anas, M., Basri, S., Chaurasiya, N., & Ali, M. (2026). Artificial Intelligence-Assisted Omics Techniques in Plant Defense: Recent Advancements and Future Prospects. 143–170. https://doi.org/10.1079/9781800628649.0007
• Artemisinin production in Artemisia annua: studies in planta and results of a novel delivery method for treating malaria and other neglected diseases. (n.d.). SpringerPJ Weathers, PR Arsenault, PS Covello, A McMickle, KH Teoh, DW ReedPhytochemistry Reviews, 2011•Springer. https://doi.org/10.1007/S10529-011-0517-0
• Assunção, M., Tedesco, S., & Fevereiro, P. (2021). Molecular aspects of grafting in woody plants. Wiley Online LibraryM Assunção, S Tedesco, P FevereiroAnnual Plant Reviews Online, 2018•Wiley Online Library, 4(1), 87–126. https://doi.org/10.1002/9781119312994.apr0751
• Athanasiadou, C., & Theriou, G. (2021). Telework: systematic literature review and future research agenda. Cell.ComC Athanasiadou, G TheriouHeliyon, 2021•cell.Com, 7(10). https://doi.org/10.1016/j.heliyon.2021.e08165
• biotechnology, D. F.-A. microbiology and, & 2007, undefined. (n.d.). Taxanes: perspectives for biotechnological production. SpringerD FrenseApplied Microbiology and Biotechnology, 2007•Springer. https://doi.org/10.1007/S00253-006-0711-3
• Bistgani, Z. E., Hashemi, M., DaCosta, M., Craker, L., Maggi, F., & Morshedloo, M. R. (2019). Effect of salinity stress on the physiological characteristics, phenolic compounds and antioxidant activity of Thymus vulgaris L. and Thymus daenensis Celak. Industrial Crops and Products, 135, 311–320. https://doi.org/10.1016/j.indcrop.2019.04.055
• Challa, G. (2018). Transcriptome Analysis of Root Development in Wheat (Triticum aestivum) Using High-throughput Sequencing Technologies. https://search.proquest.com/openview/eedff6ff506d397129e6fa0443269cd6/1?pq-origsite=gscholar&cbl=18750
• Chougule, R. N., Surveswaran, S., Yadav, S. R., & Lekhak, M. M. (2022). Medicinal potential of the Cape-pondweed family (Aponogetonaceae): A review. ElsevierRN Chougule, S Surveswaran, SR Yadav, MM
• LekhakSouth African Journal of Botany, 2022•Elsevier, 149, 994–1007. https://doi.org/10.1016/j.sajb.2022.01.023 Degl’Innocenti, E., Hafsi, C., Guidi, L., & Navari-Izzo, F. (2009). The effect of salinity on photosynthetic activity in potassium-deficient barley species. Elsevier, 166(18), 1968–1981. https://doi.org/10.1016/j.jplph.2009.06.013
• Dobhal, P., Purohit, V., Chandra, S., Rawat, S., Stress, P. P.-P., & 2024, undefined. (n.d.). Climate-induced changes in essential oil production and terpene composition in alpine aromatic plants. Elsevier. https://doi.org/10.1016/J.PLANTS.2024.100445
• Ehrlich, P., Evolution, P. R.-, & 1964, undefined. (1964a). Butterflies and plants: a study in coevolution. JSTORPR Ehrlich, PH RavenEvolution, 1964•JSTOR, 18(4), 586–608. https://www.jstor.org/stable/2406212
• Ehrlich, P., Evolution, P. R.-, & 1964, undefined. (1964b). Butterflies and plants: a study in coevolution. JSTORPR Ehrlich, PH RavenEvolution, 1964•JSTOR, 18(4), 586–608. https://www.jstor.org/stable/2406212
• Fernandes, J., Silvestre, C., Zucolotto, S., Separations, J. A.-, & 2025, undefined. (n.d.). Flavonoids as markers in herbal medicine quality control: Current trends and analytical perspective. Mdpi.Com. Retrieved February 20, 2026, from https://www.mdpi.com/2297-8739/12/11/289
• Fernie, A. R., Cavalcanti, J. H. F., & Nunes-Nesi, A. (2020). Metabolic Roles of Plant Mitochondrial Carriers. Biomolecules 2020, Vol. 10, Page 1013, 10(7), 1013. https://doi.org/10.3390/biom10071013
• Foyer, C., cell, G. N.-T. plant, & 2005, undefined. (n.d.). Redox homeostasis and antioxidant signaling: a metabolic interface between stress perception and physiological responses. Academic.Oup.ComCH Foyer, G NoctorThe Plant Cell, 2005•academic.Oup.Com. Retrieved February 20, 2026, from https://academic.oup.com/plcell/article-abstract/17/7/1866/6114571
• Gadzovska, S., Maury, S., Delaunay, A., Spasenoski, M., Hagège, D., Courtois, D., & Joseph, C. (2013). The influence of salicylic acid elicitation of shoots, callus, and cell suspension cultures on production of naphtodianthrones and phenylpropanoids in Hypericum. SpringerS Gadzovska, S Maury, A Delaunay, M Spasenoski, D Hagège, D Courtois, C JosephPlant Cell, Tissue and Organ Culture (PCTOC), 2013•Springer, 113(1), 25–39. https://doi.org/10.1007/s11240-012-0248-0
• Gao, H., Pei, X., Song, X., Wang, S., Yang, Z., Zhu, J., Lin, Q., Zhu, Q., & Yang, X. (2024). Application and development of CRISPR technology in the secondary metabolic pathway of the active ingredients of phytopharmaceuticals. Frontiers in Plant Science, 15, 1477894. https://doi.org/10.3389/fpls.2024.1477894
• Ge, G., Dai, D., Zhou, X., Wu, W., Zheng, C., Fitoterapia, X. S.-, & 2022, undefined. (n.d.). Rare isotachin-derived from the Dasymaschalon rostratum fungus Penicillium tanzanicum ZY-5. Elsevier. Retrieved February 20, 2026, from https://www.sciencedirect.com/science/article/pii/S0367326X2100294X
• Jain, S., Shrivastava, S., Anal, A. A.-… . J. Pharm. Chem., & 2024, undefined. (n.d.). WHO guidelines for quality control of herbal medicines: From cultivation to consumption. Researchgate.Net. Retrieved February 20, 2026, from https://www.researchgate.net/profile/Ankit-Agrawal-70/publication/384472754_sep_2024/links/66fb76cf869f1104c6c17ff4/sep-2024.pdf
• Jamloki, A., Bhattacharyya, M., Nautiyal, M., Heliyon, B. P.-, & 2021, undefined. (n.d.). Elucidating the relevance of high temperature and elevated CO2 in plant secondary metabolites (PSMs) production. Cell.ComA Jamloki, M Bhattacharyya, MC Nautiyal, B PatniHeliyon, 2021•cell.Com. Retrieved February 20, 2026, from https://www.cell.com/heliyon/fulltext/S2405-8440(21)01812-0
• Jangpangi, D., Patni, B., Chandola, V., & Chandra, S. (2025a). Medicinal plants in a changing climate: understanding the links between environmental stress and secondary metabolite synthesis. Frontiers in Plant Science, 16. https://doi.org/10.3389/fpls.2025.1587337
• Jangpangi, D., Patni, B., Chandola, V., & Chandra, S. (2025b). Medicinal plants in a changing climate: understanding the links between environmental stress and secondary metabolite synthesis. Frontiers in Plant Science, 16. https://doi.org/10.3389/fpls.2025.1587337
• Khan, A., Kanwal, F., Ullah, S., Fahad, M., Tariq, L., Altaf, M. T., ... & Zhang, G. (2025). Plant secondary metabolites—Central regulators against abiotic and biotic stresses. Metabolites, 15(4), 276.
• Khorasaninejad, S., Mousavi, A., Soltanloo, H., Hemmati, K., & Khalighi, A. (2011). The effect of drought stress on growth parameters, essential oil yield and constituent of Peppermint (Mentha piperita L.). Academicjournals.OrgS Khorasaninejad, A Mousavi, H Soltanloo, K Hemmati, A KhalighiJournal of Medicinal Plants Research, 2011•academicjournals.Org, 5(22), 5360–5365. https://academicjournals.org/article/article1380536853_Khorasaninejad%20et%20al.pdf
• Li, G., Xie, Q., Lin, P., Li, H., & Chen, Y. (2024). Deciphering the mechanisms of authentic medicinal herbs formation through the information perspective on gene-environment interactions. International Journal of Agriculture Innovation, Technology and Globalisation, 4(2), 121–145. https://doi.org/10.1504/ijaitg.2024.142674
• Li, L., Jiang, G., Li, H., Liu, J., Zhang, P., Wang, Q., Huang, L., Zhang, S., Wang, X., Zhang, L., Bai, Y., & Qin, P. (2024). UV-B induced flavonoid accumulation and related gene expression in blue-grained wheat at different periods of time. Frontiersin.OrgL Li, G Jiang, H Li, J Liu, P Zhang, Q Wang, L Huang, S Zhang, X Wang, L Zhang, Y BaiFrontiers in Plant Science, 2024•frontiersin.Org, 15. https://doi.org/10.3389/fpls.2024.1520543
• Li, Y., Liu, C., Shi, Q., Yang, F., & Wei, M. (2021). Mixed red and blue light promotes ripening and improves quality of tomato fruit by influencing melatonin content. ElsevierY Li, C Liu, Q Shi, F Yang, M WeiEnvironmental and Experimental Botany, 2021•Elsevier, 185. https://doi.org/10.1016/j.envexpbot.2021.104407
• Maeda, H. A., & Fernie, A. R. (2021). Evolutionary history of plant metabolism. Annualreviews.OrgHA Maeda, AR FernieAnnual Review of Plant Biology, 2021•annualreviews.Org, 72, 185–216. https://doi.org/10.1146/annurev-arplant-080620-031054
• Manafi, H., Mozafari, A. A., & Ghoran, S. H. (2024). Melatonin application in in vitro conditions may modulate the phyto-biochemical mechanisms of Hymenocrater longiflorus Benth. Under salinity stress. Plant Growth Regulation 2024 104:3, 104(3), 1465–1482. https://doi.org/10.1007/s10725-024-01233-y
• Meraj, T., Fu, J., Raza, M., Zhu, C., Shen, Q., Genes, D. X.-, & 2020, undefined. (n.d.). Transcriptional factors regulate plant stress responses through mediating secondary metabolism. Mdpi.ComTA Meraj, J Fu, MA Raza, C Zhu, Q Shen, D Xu, Q WangGenes, 2020•mdpi.Com. Retrieved February 20, 2026, from https://www.mdpi.com/2073-4425/11/4/346
• Michael, K. J., & Tomczyk, W. M. (n.d.). Flavonoids of the Caryophyllaceae. https://doi.org/10.1007/s11101-021-09755-3
• Mithöfer, A., biology, W. B.-A. review of plant, & 2012, undefined. (2012). Plant defense against herbivores: chemical aspects. Annualreviews.OrgA Mithöfer, W BolandAnnual Review of Plant Biology, 2012•annualreviews.Org, 63, 431–450. https://doi.org/10.1146/annurev-arplant-042110-103854
• Moreira, R., Pereira, D. M., Valentão, P., & Andrade, P. B. (2018). Pyrrolizidine alkaloids: chemistry, pharmacology, toxicology and food safety. Mdpi.ComR Moreira, DM Pereira, P Valentão, PB AndradeInternational Journal of Molecular Sciences, 2018•mdpi.Com, 19(6). https://doi.org/10.3390/ijms19061668
• Murthy, H. N., Lee, E. J., & Paek, K. Y. (2014). Production of secondary metabolites from cell and organ cultures: strategies and approaches for biomass improvement and metabolite accumulation. SpringerHN Murthy, EJ Lee, KY PaekPlant Cell, Tissue and Organ Culture (PCTOC), 2014•Springer, 118(1), 1–16. https://doi.org/10.1007/s11240-014-0467-7
• Neto, V. G., de Castro, R. D., Lima, B. L. S., Vieira, C. J. B., Rosário, N. L., Fernandez, L. G., Goudsmit, E., Ligterink, W., Hilhorst, H. W. M., & Ribeiro, P. R. (2021). Modulation of NF-YB genes in Ricinus communis L. in response to different temperatures and developmental stages and functional characterization of RcNF-YB8 as. ElsevierVG Neto, RD de Castro, BLS Lima, CJB Vieira, NL Rosário, LG Fernandez, E GoudsmitPlant Physiology and Biochemistry, 2021•Elsevier, 166, 20–30. https://doi.org/10.1016/j.plaphy.2021.05.014
• Nicolas-Espinosa, J., … P. G.-I.-I. J. of, & 2023, undefined. (n.d.). Confronting secondary metabolites with water uptake and transport in plants under abiotic stress. Mdpi.ComJ Nicolas-Espinosa, P Garcia-Ibañez, A Lopez-Zaplana, L Yepes-MolinaInternational Journal of Molecular Sciences, 2023•mdpi.Com. Retrieved February 20, 2026, from https://www.mdpi.com/1422-0067/24/3/2826
• Pant, P., Pandey, S., & Dall’Acqua, S. (2021). The influence of environmental conditions on secondary metabolites in medicinal plants: A literature review. Wiley Online LibraryP Pant, S Pandey, S Dall’AcquaChemistry & Biodiversity, 2021•Wiley Online Library, 18(11). https://doi.org/10.1002/cbdv.202100345
• Qaderi, M., Martel, A., Plants, C. S.-, & 2023, undefined. (2023). Environmental factors regulate plant secondary metabolites. Plants. 2023; 12: 447. Mdpi.Com. https://www.academia.edu/download/102336344/pdf.pdf
• Reshi, Z., Ahmad, W., Lukatkin, A., Metabolites, S. J.-, & 2023, undefined. (n.d.). From nature to lab: A review of secondary metabolite biosynthetic pathways, environmental influences, and in vitro approaches. Mdpi.ComZA Reshi, W Ahmad, AS Lukatkin, SB JavedMetabolites, 2023•mdpi.Com. Retrieved February 20, 2026, from https://www.mdpi.com/2218-1989/13/8/895
• Science, G. F.-, & 1959, undefined. (1959). The raison d’etre of secondary plant substances: these odd chemicals arose as a means of protecting plants from insects and now guide insects to food. Science.Org, 129(3361), 1466–1470. https://doi.org/10.1126/science.129.3361.1466
• Springer, N. M., & Schmitz, R. J. (2017). Exploiting induced and natural epigenetic variation for crop improvement. Nature Reviews Genetics 2017 18:9, 18(9), 563–575. https://doi.org/10.1038/nrg.2017.45
• Sun, Y., Alseekh, S., & Fernie, A. R. (2023). Plant secondary metabolic responses to global climate change: a meta‐analysis in medicinal and aromatic plants. Wiley Online LibraryY Sun, S Alseekh, AR FernieGlobal Change Biology, 2023•Wiley Online Library, 29(2), 477–504. https://doi.org/10.1111/gcb.16484
• Sun, Y., & Fernie, A. R. (2024). Plant secondary metabolism in a fluctuating world: climate change perspectives. Cell.ComY Sun, AR FernieTrends in Plant Science, 2024•cell.Com, 29(5), 560–571. https://doi.org/10.1016/j.tplants.2023.11.008
• Tian, X., Hu, M., Yang, J., Yin, Y., Foods, W. F.-, & 2024, undefined. (n.d.). Ultraviolet-B radiation stimulates flavonoid biosynthesis and antioxidant systems in buckwheat sprouts. Mdpi.ComX Tian, M Hu, J Yang, Y Yin, W FangFoods, 2024•mdpi.Com. Retrieved February 20, 2026, from https://www.mdpi.com/2304-8158/13/22/3650
• van der Linden, C. F. H., WallisDeVries, M. F., & Simon, S. (2021). Great chemistry between us: The link between plant chemical defenses and butterfly evolution. Wiley Online LibraryCFH van Der Linden, MF WallisDeVries, S SimonEcology and Evolution, 2021•Wiley Online Library, 11(13), 8595–8613. https://doi.org/10.1002/ece3.7673
• Xu, L., sciences, X. W.-I. journal of molecular, & 2025, undefined. (2025). A comprehensive review of phenolic compounds in horticultural plants. Mdpi.ComL Xu, X WangInternational Journal of Molecular Sciences, 2025•mdpi.Com, 26(12). https://doi.org/10.3390/ijms26125767
• Xu, S., & Gaquerel, E. (2025). Evolution of plant specialized metabolites: beyond ecological drivers. Trends in Plant Science.
• York, F. G.-S. (New, NY), undefined, & 1959, undefined. (1959). The raison d’ĕtre of secondary plant substances; these odd chemicals arose as a means of protecting plants from insects and now guide insects to food. Europepmc.Org, 129(3361), 1466–1470. https://doi.org/10.1126/science.129.3361.1466
• Zandalinas, S. I., Balfagón, D., Gómez-Cadenas, A., & Mittler, R. (2022). Responses of plants to climate change: metabolic changes during abiotic stress combination in plants. J. Exp. Bot, 73(11), 3339-3354.
• Zhao, J., Davis, L., advances, R. V.-B., & 2005, undefined. (n.d.). Elicitor signal transduction leading to production of plant secondary metabolites. ElsevierJ Zhao, LC Davis, R VerpoorteBiotechnology Advances, 2005•Elsevier. Retrieved February 21, 2026, from https://www.sciencedirect.com/science/article/pii/S0734975005000182