Influence of pyrrolizidine alkaloids depletion upon the biological activity of Symphytum officinale L. extracts. (1st March 2023)

• Record Type: Journal Article
• Authors: Trifan, Adriana; Czerwińska, Monika E.; Zengin, Gokhan; Esslinger, Nils; Grubelnik, Andreas; Wolfram, Evelyn; Skalicka-Woźniak, Krystyna; Luca, Simon Vlad
• Is Part Of: Journal of ethnopharmacology. Volume 303(2023)
• Publication Date: 2023-03-01
• Subjects: Symphytum officinale -- Pyrrolizidine alkaloids -- Depletion -- Globoidnan -- Pro-inflammatory cytokines; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2022.116010
• Languages: English
• ISSNs: 0378-8741

Abstract

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-1 β, 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-1 β, 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. Graphical abstract: Image 1 Highlights: Various PA/mucilage-depleted comfrey root extracts were obtained. Phenolic acids, organic acids, fatty acids and sugars were detected by LC-HRMS/MS. PAs were below 2 ppm in PA-depleted extracts. PA-depleted extracts exhibited IL-1β, IL-8 and TNF-α inhibitory properties in LPS-stimulated neutrophils. Bioactive PA-depleted extracts can be considered safer alternatives to raw comfrey extracts.