Discovery of phloroglucinols from Hypericum japonicum as ferroptosis inhibitors

• Published in: Fitoterapia 2021-09, Vol.153, p.104984, Article 104984
• Main Authors: Peng, Xing, Tan, Qingyun, Zhou, Huihao, Xu, Jun, Gu, Qiong
• Format: Article
• Language: English
• Subjects: Antioxidant effect; Antioxidants; Cell death; Evaluation; Ferroptosis; Ferroptosis inhibitor; Free radicals; Hypericum japonicum; Neurological diseases; Phloroglucinols; Scavenging; X-ray diffraction
• ISSN: 0367-326X; 1873-6971
• DOI: 10.1016/j.fitote.2021.104984

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. [Display omitted] •Thirteen phloroglucinols including three new ones were isolated.•Phloroglucinols exhibited significant anti-ferroptosis activity.•Compound 2 exhibited most potent anti-ferroptosis activity with EC50 value of 0.48 μM.