Risk of contamination of medicinal plant raw materials with pyrrolizidine alkaloids
DOI:
https://doi.org/10.33730/2310-4678.2.2025.337138Keywords:
Symphytum officinale L., hepatotoxicity, quality, pharmacological safety, toxic compounds, carcinogenicity, contamination, economic consequencesAbstract
Pyrrolizidine alkaloids (PAs) are secondary metabolites found in certain plant species, particularly members of the families Boraginaceae (comprising 115 genera and approximately 2,500 species), Asteraceae (1,000 genera and 20,000 species), and Fabaceae (700 genera and 17,000 species). These compounds exhibit pronounced hepatotoxic, genotoxic, and potentially carcinogenic effects. The presence of PAs in medicinal plant raw materials can result from contamination by plant fragments from these families during harvesting, as well as horizontal transfer of compounds in the soil. This article analyzes several toxicological properties of PAs, along with their mechanisms of entry into medicinal plant raw materials, common sources, and risks associated with the use of phytomaterials that may contain these compounds. Special attention is given to the biodiversity of PA-accumulating plants in Ukraine, particularly common comfrey (Symphytum officinale), as well as plant materials that are potentially contaminated with PAs. The risks of cross-contamination during harvesting, drying, transportation, and initial processing of medicinal raw materials are evaluated. The study also emphasizes the necessity of implementing international GACP standards to reduce contamination risks. Examples of economic consequences resulting from PAs contamination are presented, and the importance of a comprehensive approach to quality control in medicinal plant raw materials is highlighted. The research findings underscore the need for systematic monitoring of PAs content in medicinal raw materials, both at the stage of wild plant collection and during pharmaceutical production, to ensure the safety and efficacy of herbal medicinal products.
References
Danylko, R., & Kliuchevych, M. (2024). Control of pyrrolizidine alkaloids in medicinal plant raw materials. In Scientific Horizons of the 21st Century: Multidisciplinary Research: Proceedings of the International Scientific Conference (Uzhhorod, May 16–17, 2024) (p. 139).
Kopp, T., Abdel-Tawab, M., & Mizaikoff, B. (2020). Extracting and analyzing pyrrolizidine alkaloids in medicinal plants: A review. Toxins, 12(5), 320. doi: 10.3390/toxins12050320
Al-Subaie, S. F., Alowaifeer, A. M., & Mohamed, M. E. (2022). Pyrrolizidine alkaloid extraction and analysis: Recent updates. Foods, 11(23), 3873. doi: 10.3390/foods11233873
Steinhoff, B. (2019). Pyrrolizidine alkaloid contamination in herbal medicinal products: Limits and occurrence. Food and Chemical Toxicology, 130, 262–266. doi: 10.1016/j.fct.2019.05.026
Jayawickreme, K., Świstak, D., Ozimek, E., Reszczyńska, E., Rysiak, A., Makuch-Kocka, A., & Hanaka, A. (2023). Pyrrolizidine alkaloids — Pros and cons for pharmaceutical and medical applications. International Journal of Molecular Sciences, 24(23), 16972. doi: 10.3390/ijms242316972
Wiesner, J. (2022). Regulatory perspectives of pyrrolizidine alkaloid contamination in herbal medicinal products. Planta Medica, 88(2), 118–124. doi: 10.1055/a-1494-1363
Wang, W., Chen, Y., Yin, Y., Wang, X, Ye, X, Jiang, K, … Wang, Z. (2022). A TMT-based shotgun proteomics uncovers overexpression of thrombospondin 1 as a contributor in pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome. Archives of Toxicology, 96(7), 2003–2019.
Tábuas, B., Cruz Barros, S., Diogo, C., Cavaleiro, C., & Sanches Silva, A. (2024). Pyrrolizidine alkaloids in foods, herbal drugs, and food supplements: Chemistry, metabolism, toxicological significance, analytical methods, occurrence, and challenges for future. Toxins, 16(2), 79. doi: 10.3390/toxins16020079
Fernández-Pintor, B., Casado, N., Morante-Zarcero, S., & Sierra, I. (2023). Evaluation of the thermal stability and transfer rate of pyrrolizidine alkaloids during the brewing of herbal infusions contaminated with Echium vulgare and Senecio vulgaris weeds. Food Control, 154, 109926. doi: 10.1016/j.foodcont.2023.109926
Steinhoff, B. (2022). Pyrrolizidine alkaloid contamination in medicinal plants: Regulatory requirements and their impact on production and quality control of herbal medicinal products. Planta Medica, 88(2), 125–129. doi: 10.1055/a1494-3623
Kakar, F., Akbarian, Z., Leslie, T., Mustafa, M. L., Watson, J., van Egmond, H. P., … Mofleh, J. (2010). An outbreak of hepatic veno‐occlusive disease in western Afghanistan associated with exposure to wheat flour contaminated with pyrrolizidine alkaloids. Journal of Toxicology, 2010, 313280. doi: 10.1155/2010/313280
Hryhora, I. M., & Solomakha, V. A. (2000). Fundamentals of phytocenology. Kyiv: Phytotsotsiocentr.
Popovych, S. Yu., Bairak, O. M., Vasheka, L. V., et al. (2018). Geobotany: Methodological aspects of research. Kyiv: Lira.
Kyrian, V. M., Hlushchenko, L. A., Tryhub, O. V., & Bohuslavskyi, R. L. (2017). Genetic resources of cultivated and wild plants of the Central Forest-Steppe of Ukraine. Genetic Resources of Plants, 2, 11–26.
Kirian, V. M., Hlushchenko, L. A., & Bohuslavskyi, R. L. (2018). Gene pool of plants of the Ukrainian Forest-Steppe. Genetic Resources of Plants, 23, 11–31.
Kyrian, V. M., Hlushchenko, L. A., Bohuslavskyi, R. L., & Hlushchenko, Yu. V. (2019). Genetic diversity of plants in the Northeastern regions of Ukraine. Plant Genetic Resources, 2(24), 26–46.
Kyrian, V. M., Hlushchenko, L. A., Hlushchenko, Yu. V., & Bohuslavskyi, R. L. (2019). Genetic resources of plants of Podillia region, Ukraine (based on the results of the 2019 expedition). Plant Genetic Resources, 3(25), 41–61.
Kyrian, V. M., Hlushchenko, L. A., & Bohuslavskyi, R. L. (2021). Genetic resources of plants in Dnipropetrovsk and Kharkiv regions. Plant Genetic Resources, 1(28), 19–35. doi: 10.36814/pgr.2021.28.02
Kyrian, V. M., Hlushchenko, L. A., & Bohuslavskyi, R. L. (2022). Genetic diversity of plants in Chernivtsi and Ternopil regions of Ukraine. Plant Genetic Resources, 1(30), 22–33. doi: 10.36814/pgr.2022.30.02
Didukh, Ya. P. (1998). Population ecology. Kyiv: Phytotsotsiocentr.
Minarchenko, V. M., & Minarchenko, O. M. (2004). Methodology for accounting plant resources (40 p.). Kyiv
Mosiakin, S. L., & Fedoronchuk, M. M. (1999). Vascular plants of Ukraine: A nomenclatural checklist. Kyiv: M. G. Kholodny Institute of Botany.
Kotov, M. I., Prokudin, Yu. N., et al. (1987). Key to higher plants of Ukraine. Kyiv: Naukova dumka.
van Dam, N. M., Verpoorte, R., & van der Meijden, E. D. (1994). Extreme differences in pyrrolizidine alkaloid levels between leaves of Cynoglossum officinale. Phytochemistry, 37(4), 1013–1016.
Popova, N. V., Lytvynenko, V. I., & Kutsanyan, A. S. (2016). Medicinal plants of the world flora: Encyclopedic reference. Kharkiv: Disa Plius.
European Pharmacopoeia (12th ed.). (2025). Strasbourg: EDQM.
State Pharmacopoeia of Ukraine. (2nd ed.). (2020). Kharkiv: SE “NEFC”.
Kotov, A. H., Kotova, Ye. Ye., & Sokolova, O. O. (2021). Atlas of illustrations for methods of identification of medicinal plant raw materials in the national monographs of the State Pharmacopoeia of Ukraine.
European Medicines Agency. (2006). Guideline on good agricultural and collection practice (GACP) for starting materials of herbal origin. London.
Downloads
Published
Issue
Section
License
- The authors reserve the right to authorship their work and pass the journal the right to publish this work under a Creative Commons Attribution License license, which allows other persons to freely distribute the published work with the obligatory The authors of the original work and the first publication of this magazine.
- The authors have the right to make independent additional agreements on the nonexclusive dissemination of the work in the form in which it was published by this magazine (for example, to post work in the company's electronic storage or to publish as a monograph) , subject to the first publication of the link to this journal.
- Journal policy allows and encourages the placement of authors on the Internet (for example, in the repositories of institutions or on personal websites) manuscript work as to the presentation of this manuscript to the editorial board and during its editorial processing, as it contributes to The productive scientific discussion and positively affects the efficiency and dynamics of citation published work (see The Effect of Open Access).