The aerial parts of Epilobium angustifolium L. (fireweed) (Onagraceae) are renowned for their use in the treatment of prostatic, kidney and urinary tract diseases, and skin infections. In this work, a comprehensive phytochemical profiling of the methanol-aqueous extract from E. anfustifolium aerial parts was performed by the means of liquid chromatography-Orbitrap high-resolution mass spectrometry. Annotation and dereplication of 121 secondary metabolites were achieved, including acylquinic acids, gallo- and ellagitannins, flavonoids, phenolic acids, and their glycosides. Forty-six compounds are reported for the first time in the species. Total phenolic and flavonoid content were 85.04 ± 0.18 mg GAE/g and 27.71 ± 0.74 mg QE/g, respectively. Antioxidant capacity assessment revealed that the extract actively scavenged DPPH and ABTS radicals (310.74 and 466.82 mg TE/g) along with a high reducing power in CUPRAC and FRAP assay (442.83 and 291.50 mg TE/g), respectively, and metal chelating (48.20 mg EDTA/g). The extract also had a distinct impact on α-glucosidase (3.48 mmol ACAE/g) and moderate activity towards α-amylase (0.44 mmol ACAE/g) and lipase (8.03 OE/g). It inhibited acetyl- and butyrylcholinesterase (2.05 and 1.67 mg GALE/g) and had a prominent anti-tyrosinase effect (61.91 mg KA/g). Our results contribute to establishing fireweed as a multifunctional agent for use in herbal preparations.
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