Phenolic glycosides from Ligusticum wallichii with cytotoxic activity

Ligusticum wallichii Franch. (Apiaceae) is a traditional medicinal plant extensively used in Asia for treating circulatory and neurological disorders. Two new phenolic glycosides, ligusticosides A and B ( 1 and 2 ), along with five known compounds, 2-methoxy-4-(3-methoxy-1-propenyl)-phenol ( 3 ), ferulic acid ( 4 ), coniferin ( 5 ), 2-methoxy-2-(4′-hydroxyphenyl)ethanol ( 6 ), and falcarindiol ( 7 ) were isolated from the roots of L. wallichii. The chemical structures of the isolated compounds were elucidated by comprehensive spectroscopic and chemical analyses, including NMR and HR-ESI-MS. All compounds were evaluated for cytotoxic activity by the MTS assay on PC9 (lung), A2058 (melanoma), and HepG2 (liver) cancer cell lines. Compounds 1 , 2 , 5 , and 7 exhibited significant cytotoxic activity with IC₅₀ values ranging from 3.2 to 9.8 µM against the tested cell lines. Compounds 1 , 2 , 5 , and 7 also significantly increased caspase-3 activity (2.52–3.20-fold) and PARP-1 cleavage (2.41–2.88-fold), indicating apoptosis as a major mechanism of action. • Two new ligusticosides A and B ( 1 and 2 ) were isolated from the roots of Ligusticum wallichii. • The structures were successfully determined by spectroscopic evidence. • Compounds 1 , 2 , 5 , and 7 exhibited significant cytotoxic activity with IC₅₀ values from 3.2 to 9.8 µM on tested cell lines. • Compounds 1 , 2 , 5 , and 7 significantly increased caspase-3 activity and PARP-1 cleavage.