Skin microbiota metabolism of natural products from comfrey root (Symphytum officinale L.)

Abstract

Ethnopharmacological relevance: Comfrey root (Symphytum officinale L., Boraginaceae) has been used in folk medicine for a long time to treat different diseases. It is recommended for swellings, phlebitis, contusions, gastro-duodenal ulcers, respiratory diseases, and metrorrhagia. Currently, preparations from S. officinale are only topically used due to its wound-healing effects, and for reducing inflammation and the treatment of broken bones, tendon damage, painful joints and muscles. Although it is a widespread plant material, little is known about the interaction of externally applied preparations of comfrey with the human skin microbiome.

Aim of the study: The study aims to determine the interaction between human skin microbiota and the comfrey root extracts, by monitoring the biotransformation of the constituents present in the extract and evaluating changes in the population of the skin microbiota in an ex vivo setting.

Material and methods: The comfrey root extract was incubated with the human skin microbiota from ten healthy donors. The UHPLC-DAD-MSⁿ analysis determined the composition of the raw extract and the microbial metabolites. Bacterial genomic DNA was extracted and examined by amplification sequencing of the 16S rDNA to determine changes in the bacterial composition.

Results: The hydroethanolic extract of comfrey root primarily consists of phenolic acids, pyrrolizidine alkaloids, and their derivatives, and lignans. The natural products present in the extract underwent biodegradation by the skin microbiota, leading to the formation of smaller molecules. It was observed that the skin microbial metabolism primarily focused on modifying the derivatives of pyrrolizidine alkaloids. It resulted in the production of deacetylated and deesterificated compounds. However, it did not lead to the conversion of these compounds into free alkaloids.

Conclusions: The microbiota-triggered biotransformation of the comfrey root extract was observed. A few N-oxides were metabolized to deacetylated and deesterificated forms in ex vivo conditions. It suggests that the intermittent external applications of comfrey preparations perchance are unlikely to pose a substantial risk. While it even may serve as a potential factor influencing the extract activity in treating skin diseases.

Keywords: Comfrey; Metabolism; Pyrrolizidine alkaloids; Skin microbiota; Symphytum officinale.