Lin Yang,Yangping Liu,Wenhui Zhang,Yujie Hua,Ban Chen,Quanzhou Wu,Dongfeng Chen,Shuqin Liu,Xican Li
The search for a safe and effective inhibitor of ferroptosis, a recently described cell death pathway, has attracted increasing interest from scientists. Two hydrolyzable tannins, chebulagic acid and chebulinic acid, were selected for the study. Their optimized conformations were calculated using computational chemistry at the B3LYP-D3(BJ)/6-31G and B3LYP-D3(BJ)/6-311 + G(d,p) levels. The results suggested that (1) chebulagic acid presented a chair conformation, while chebulinic acid presented a skew-boat conformation; (2) the formation of chebulagic acid requires 762.1729 kcal/mol more molecular energy than chebulinic acid; and (3) the 3,6-HHDP (hexahydroxydiphenoyl) moiety was shown to be in an (R)- absolute stereoconfiguration. Subsequently, the ferroptosis inhibition of both tannins was determined using a erastin-treated bone marrow-derived mesenchymal stem cells (bmMSCs) model and compared to that of ferrostatin-1 (Fer-1). The relative inhibitory levels decreased in the following order: Fer-1 > chebulagic acid > chebulinic acid, as also revealed by the in vitro antioxidant assays. The UHPLC–ESI-Q-TOF-MS analysis suggested that, when treated with 16-(2-(14-carboxytetradecyl)-2-ethyl-4,4-dimethyl-3-oxazolidinyloxy free radicals, Fer-1 generated dimeric products, whereas the two acids did not. In conclusion, two hydrolyzable tannins, chebulagic acid and chebulinic acid, can act as natural ferroptosis inhibitors. Their ferroptosis inhibition is mediated by regular antioxidant pathways (ROS scavenging and iron chelation), rather than the redox-based catalytic recycling pathway exhibited by Fer-1. Through antioxidant pathways, the HHDP moiety in chebulagic acid enables ferroptosis-inhibitory action of hydrolyzable tannins.Keywords:ferroptosis-inhibition;ferrostatin-1;chebulagic acid;chebulinic acid;hydrolyzable tannin;HHDP
Peng-Cheng Guo,Hua-Dan Shen,Jiang-Ji Fang,Tian-Ming Ding,Xiao-Ping Ding,Jun-Feng Liu
An on-line high-performance liquid chromatography–biochemical detection (HPLC-BCD) method, in which compounds separated by HPLC were on-line reacted with enzyme and substrate solutions delivered by flow injection and the enzyme inhibition signal was collected by UV detection, was developed to rapidly screen α -glucosidase inhibitors from green tea extracts in this study. The chromatographic fingerprints and enzyme inhibition profiles of the different brands of green tea could be simultaneously detected by the on-line HPLC-BCD method. Enzyme inhibition profiles were detected by the UV detector at 415 nm based on the reaction of α -glucosidase and p -nitrophenyl α - d -glucopyranoside (PNPG). PNPG (1.25 m m ), α -glucosidase (0.4 U/mL) and the flow rate 0.07 mL/min were applied as optimized parameters to detect α -glucosidase inhibitors in green tea. Four components in green tea showed α -glucosidase inhibition action and three of them were identified as HHDP-galloyl glucose, (−)-epigallocatechin-3-gallate and (−)-epicatechin-3-gallate by HPLC–fourier-transform mass spectrometry (HPLC-FTMS). Two brands of green tea derived from Mengding and Enshi mountainous areas might be superior to the other samples in the prevention and treatment of diabetes owing to their stronger activities of enzyme inhibitors. The proposed on-line HPLC-BCD method could be used to rapidly identify the potential enzyme inhibitors in complex matrixes.
危险品化学品经营许可证（带存储）