Polyphenols are attracting increasing attention to the discovery of useful agents for the treatment of neurodegenerative diseases.

Thelesperma megapotamicum (Spreng.) Kuntze belongs to the family Asteraceae which is known to have a high antioxidant capacity.

The phytochemical investigation of T. megapotamicum revealed the presence of 1’-S-acetoxyeugenol isobutyrate (1), 1’-S-isobutyroxyeugenol isobutyrate (2), stigmasterol (3), b-sitosterol (4), lupeol (5), luteolin (6), eriodictyol (7), and marein (8), as major secondary metabolites. Compounds 1-5, and 7 were isolated for the first time from T. megapotamicum.

The neuroprotective activity of this species was studied by evaluating the inhibition in vitro of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and antioxidant capacity of the sub-extracts and of the major metabolites isolated from them. The AChE and BChE inhibition were determined by Ellman’s method and the antioxidant activity by DPPH assay.

The chloroform (IC₅₀ = 30.7 ± 1.5 μg/mL) and n-butanol sub-extracts (IC₅₀ = 60.3 ± 2.3 μg/mL) were the most active against BChE. Metabolites 1, 2 and 8, isolated from these sub-extracts, exhibited the highest activity against this enzyme, with IC₅₀ values of 59.0 ± 2.1 μM, 46.4 ± 1.2 μM, and 51.6 ± 2.3 μM, respectively.

The ethyl acetate (IC₅₀ = 19.6 ± 0.7 μg/mL) and n-butanol sub-extracts (IC₅₀ = 49.5 ± 2.2 μg/mL) showed an interesting antioxidant activity. Compounds 6, 7 and 8, obtained from these sub-extracts, were the most active, with IC₅₀ values of 19.1 ± 2.8 μM, 17.9 ± 1.2 μM, and 78.6 ± 1.7 μM, respectively.

The inhibitory activity against BChE and antioxidant capacity of the polyphenols present in T. megapotamicum highlight this species as a promising source of active metabolites for the development of agents for the treatment of neurodegenerative diseases.