Influence of pyrrolizidine alkaloids depletion upon the biological activity of Symphytum officinale L. extracts

Trifan, Adriana; Czerwińska, Monika E; Zengin, Gokhan; Esslinger, Nils; Grubelnik, Andreas; Wolfram, Evelyn; Skalicka-Woźniak, Krystyna; Luca, Simon Vlad

doi:10.1016/j.jep.2022.116010

Publication type:	Article in scientific journal
Type of review:	Peer review (publication)
Title:	Influence of pyrrolizidine alkaloids depletion upon the biological activity of Symphytum officinale L. extracts
Authors:	Trifan, Adriana Czerwińska, Monika E Zengin, Gokhan Esslinger, Nils Grubelnik, Andreas Wolfram, Evelyn Skalicka-Woźniak, Krystyna Luca, Simon Vlad
et. al:	No
DOI:	10.1016/j.jep.2022.116010
Published in:	Journal of Ethnopharmacology
Volume(Issue):	303
Issue:	116010
Issue Date:	1-Mar-2023
Publisher / Ed. Institution:	Elsevier
ISSN:	0378-8741 1872-7573
Language:	English
Subjects:	Depletion; Globoidnan; Pro-inflammatory cytokines; Pyrrolizidine alkaloids; Symphytum officinale; Chromatography, Liquid; Antioxidants; Monophenol monooxygenase; Interleukin-8; Lipopolysaccharides; Tumor necrosis factor-alpha; Tandem mass spectrometry; Plant extracts; Phytochemicals; Comfrey; Pyrrolizidine alkaloids; Boraginaceae
Subject (DDC):	615: Pharmacology and therapeutics
Abstract:	Ethnopharmacological relevance: Comfrey (Symphytum officinale L., Boraginaceae) root preparations are used as both traditional remedies and therapeutic agents in treating pain and inflammation associated with joint, bone, and muscle ailments. Even though numerous phytochemicals contribute to the beneficial effects of comfrey, the presence of toxic pyrrolizidine alkaloids (PAs) overshadows its uses. Aim of the study: In this work, different PA-/mucilage-depleted/undepleted comfrey root extracts were subjected to detailed phytochemical characterization and biological evaluation. Materials and methods: The phytochemical profiling was performed by LC-HRMS/MS. The quantification of PAs and major phenolic compounds was carried out by LC-MS/MS and LC-DAD. Antioxidant and enzyme inhibitory activity was determined by in vitro free radical scavenging, ion reducing, metal chelating, cholinesterase, tyrosinase, amylase, and glucosidase assays. Using an ex vivo model of LPS-stimulated neutrophils, their viability (as measured by flow cytometry) and the release of IL-1β, IL-8, and TNF-α were determined (ELISA assay). Results: 12 phenolic acids, six PAs, three organic acids, two fatty acids, and two sugars were identified in the obtained comfrey extracts. The PA-depleted materials contained PAs levels below 2 ppm, whereas the removal of mucilage increased the content of rosmarinic acid, globoidnan A, globoidnan B, and rabdosiin. PA-depletion did not significantly affect the antioxidant potential. However, the radical scavenging and metal reducing properties were higher in the mucilage-depleted extracts. Neither PA-depletion nor mucilage-depletion had considerable effects on the in vitro inhibitory activity of cholinesterases, tyrosinase, amylase, and glucosidase or release of ex vivo pro-inflammatory cytokines (e.g., IL-1β, IL-8, and TNF-α) in LPS-stimulated neutrophils. Conclusions: In light of their superior safety profiles, PA-depleted comfrey extracts can be utilized further in cosmetic and pharmaceutical products.
URI:	https://digitalcollection.zhaw.ch/handle/11475/30017
Fulltext version:	Published version
License (according to publishing contract):	Licence according to publishing contract
Departement:	Life Sciences and Facility Management
Organisational Unit:	Institute of Chemistry and Biotechnology (ICBT)
Appears in collections:	Publikationen Life Sciences und Facility Management

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Trifan, A., Czerwińska, M. E., Zengin, G., Esslinger, N., Grubelnik, A., Wolfram, E., Skalicka-Woźniak, K., & Luca, S. V. (2023). Influence of pyrrolizidine alkaloids depletion upon the biological activity of Symphytum officinale L. extracts. Journal of Ethnopharmacology, 303(116010). https://doi.org/10.1016/j.jep.2022.116010

Trifan, A. et al. (2023) ‘Influence of pyrrolizidine alkaloids depletion upon the biological activity of Symphytum officinale L. extracts’, Journal of Ethnopharmacology, 303(116010). Available at: https://doi.org/10.1016/j.jep.2022.116010.

A. Trifan et al., “Influence of pyrrolizidine alkaloids depletion upon the biological activity of Symphytum officinale L. extracts,” Journal of Ethnopharmacology, vol. 303, no. 116010, Mar. 2023, doi: 10.1016/j.jep.2022.116010.

TRIFAN, Adriana, Monika E CZERWIŃSKA, Gokhan ZENGIN, Nils ESSLINGER, Andreas GRUBELNIK, Evelyn WOLFRAM, Krystyna SKALICKA-WOŹNIAK und Simon Vlad LUCA, 2023. Influence of pyrrolizidine alkaloids depletion upon the biological activity of Symphytum officinale L. extracts. Journal of Ethnopharmacology. 1 März 2023. Bd. 303, Nr. 116010. DOI 10.1016/j.jep.2022.116010

Trifan, Adriana, Monika E Czerwińska, Gokhan Zengin, Nils Esslinger, Andreas Grubelnik, Evelyn Wolfram, Krystyna Skalicka-Woźniak, and Simon Vlad Luca. 2023. “Influence of Pyrrolizidine Alkaloids Depletion upon the Biological Activity of Symphytum Officinale L. Extracts.” Journal of Ethnopharmacology 303 (116010). https://doi.org/10.1016/j.jep.2022.116010.

Trifan, Adriana, et al. “Influence of Pyrrolizidine Alkaloids Depletion upon the Biological Activity of Symphytum Officinale L. Extracts.” Journal of Ethnopharmacology, vol. 303, no. 116010, Mar. 2023, https://doi.org/10.1016/j.jep.2022.116010.