Chemical constituents of Ajuga forrestii and their anti-ferroptosis activity.

Six new neoclerodane diterpenoids (1-6), along with ten known compounds (7-16), were isolated from Ajuga forrestii. Their structures were elucidated by HRESIMS, 1D and 2D NMR, ECD calculation, and single-crystal X-ray diffraction analysis. The structure of a known neoclerodane diterpene ajudecunoid C (6) was revised based on the reported NMR empirical rules. All the isolates were evaluated for their inhibitory effect on RSL3-induced ferroptosis in HT22 mouse hippocampal neuronal cells. Among them, compounds 8, 9, and 12 significantly inhibited RSL3-induced ferroptosis with EC50 values of 0.45 µM, 0.076 µM, and 0.14 µM.

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 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.

Structure-Activity Relationship Analysis on Antioxidant and Anticancer Actions of Theaflavins on Human Colon Cancer Cells.

The roles of natural products as effective cancer prevention and therapeutic agents have been documented by various studies in recent years, but the action mechanisms and structure-activity relationship need more elucidation. The present study showed that theaflavins (theaflavin and its derivatives, TFs) from black tea caused an inhibitory effect on the proliferation of human colon adenocarcinoma cancer SW480 cells and human colon cancer SW620 cells [half maximal inhibitory concentration (IC50) < 32.0 µM] by the induction of cell cycle arrest but exerted lower toxicity against normal cells with a high safety index (1.89-6.26). Moreover, TFs triggered a decrease in reactive oxygen species in SW480 cells as a result of their excellent radical-scavenging ability (e.g., the IC50 value of TF4 to ABTS• + was 1.91 ± 0.21 µM). More importantly, the structure-activity relationship analysis of TFs exhibited that the galloyl group was an important factor to affect these activities. Taken together, we revealed that the TFs could act as substitutes for natural antioxidants and promising anticancer agents with beneficial influence on human health and then anticipated that this study may provide useful information on the development of therapeutic natural products.