Triadenosides A–F, benzophenone rhamnosides from Triadenum japonicum and their anti-ferroptosis activity

Abstract

Previously undescribed benzophenone rhamnosides, triadenosides A–F (1–6), were isolated from the aerial parts of Triadenum japonicum (Blume) Makino (Hypericaceae), where known compounds including benzophenone rhamnosides (7 and 8), benzophenone C-glucoside (9), flavonols and their glycosides (10–17), and biflavone (18) were also isolated and identified. Detailed spectroscopic analysis revealed that triadenoside A (1) was 2,3′,5′-trihydroxy-4,6-dimethoxybenzophenone 2-O-α-L-rhamnopyranoside, while the absolute configuration of the rhamnosyl moiety was confirmed by HPLC analysis. Triadenosides B–E (2–5) were assigned as acetyl derivatives of 1 in their rhamnosyl moieties. In contrast, triadenoside F (6) was elucidated to be 2,3′,5′,6-tetrahydroxy-4-methoxybenzophenone 2-O-α-L-(4″-O-acetyl)rhamnopyranoside. Compounds 1–18 isolated from T. japonicum as well as some benzophenone derivatives (5a–5e, 6a, and 8a) prepared from 5, 6, and 8 were evaluated for their inhibitory activity against RSL3-induced ferroptosis on human hepatoma Hep3B cells, showing significant inhibitory effects of triadenosides A–E (1–5) and their derivatives (5c, 5d, and 5e) with EC₅₀ values ranging from 18.0 to 41.4 nM comparable to that of a ferroptosis inhibitor, ferrostatin-1, whereas triadenoside F (6) did not exhibit such activity.