Discovery of phloroglucinols from Hypericum japonicum as ferroptosis inhibitors

Abstract Ferroptosis is a new type of cell death, which involves central neuronal system. Inhibition of ferroptosis is a promising strategy to prevent and treat neurological diseases. Thirteen phloroglucinols (1−13) were obtained from the whole plants of Hypericum japonicum. Of them, compounds 1–3 are new ones. Their structures were elucidated by extensive analysis of spectroscopic data and X-ray diffraction. All the isolates were evaluated for their inhibitory effect on RSL3-induced ferroptosis. Two new compounds 2–3 showed significant inhibitory effect with EC50 of 0.48 ± 0.14 μM and 0.94 ± 0.14 μM, respectively. DPPH free radical scavenging abilities of all compounds were assessed to evaluate their antioxidant effect. This work first reports the anti-ferroptosis activity of phloroglucinols.