Ferroptosis Inhibitory Aromatic Abietane Diterpenoids from Ajuga decumbens and Structural Revision of Two 3,4-Epoxy Group-Containing Abietanes.
Xing PengQingyun TanLeiming WuDeyin WuJun XuHuihao ZhouQiong GuPublished in: Journal of natural products (2022)
Two new 3,4-epoxy group-containing abietane diterpenoids ( 1 and 2 ), together with five known diterpenoids ( 3 - 7 ), were isolated from Ajuga decumbens . Their structures were elucidated by spectroscopic data analysis, NMR calculations, and X-ray diffraction experiments. The structures of two known abietane diterpenoids were revised based on NMR calculations and X-ray diffraction data. Notably, compound 4 specifically inhibited RSL3-induced ferroptosis with an EC 50 of 56 nM by antioxidation. Moreover, 4 significantly decreased RSL3-induced lipid and cytosolic ROS accumulation and ferroptosis marker gene PTGS2 mRNA expression. This work reports the most potent natural inhibitor against ferroptosis found so far.
Keyphrases
- cell death
- high resolution
- data analysis
- high glucose
- diabetic rats
- magnetic resonance
- density functional theory
- electron microscopy
- molecular dynamics
- molecular dynamics simulations
- total knee arthroplasty
- drug induced
- emergency department
- mass spectrometry
- solid state
- dna damage
- dual energy
- electronic health record
- machine learning
- copy number
- oxidative stress
- crystal structure
- reactive oxygen species
- computed tomography