Discovery of phloroglucinols from Hypericum japonicum as ferroptosis inhibitors

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 mu M and 0.94 +/- 0.14 mu M, 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.

Automated summary

Thirteen phloroglucinols were isolated from Hypericum japonicum, with compounds 2-3 showing significant inhibitory effects on ferroptosis induced by RSL3. This study highlights the potential anti-ferroptosis activity of phloroglucinols as a promising strategy for treating neurological diseases.