Symphytum genus—from traditional medicine to modern uses: an update on phytochemistry, pharmacological activity, and safety

Abstract

With around 34 recognized species, Symphytum genus (comfrey) has a noteworthy position within the Boraginaceae family. Comfrey species have been empirically used since ancient times as wound-healing and skin-regenerating agents in ulcers, wounds, bone fractures, and rheumatic complaints. This review aims to provide a thorough examination of recent scientific advances and challenges within the Symphytum genus, covering data published between 2013 and 2023. It delivers an updated overview of the taxonomy, ethnopharmacological uses, chemical composition, and pharmacological activities of the genus. Special emphasis is put on molecular identification methods for species taxonomy, emerging extraction technologies for comfrey phytochemicals, metabolomics techniques for mapping chemical complexity, modern bioassay platforms revealing its poly-pharmacology, formulation strategies, and remediation approaches for removal of toxic pyrrolizidine alkaloids (PAs). For instance, recent metabolomic studies employing advanced spectro-chromatographic techniques have revealed a diverse chemical composition of comfrey plants, including polysaccharides, allantoin, benzoic and cinnamic acid derivatives, flavonoids, fatty acids, and unsaturated necine-structure-based PAs. The mechanisms underlying their anti-inflammatory, analgesic, wound-healing, anti-irritant, and osteo-regenerative properties were targeted in modern pharmacological setups. Thus, key compounds like allantoin, rosmarinic acid, globoidnans A and B, rabdosiin, and comfreyn A, have been identified as significant contributors to the anti-inflammatory and wound-healing effects of Symphytum-derived preparations. Despite their well-established clinical use, concerns about PAs-induced toxicity have prompted the development of novel PA remediation strategies, enabling the production of comfrey extracts with enhanced safety profiles that can meet the regulatory standards imposed by authorities.