Bioactive peptides derived from inhibit ferroptosis in HT22 cells through direct Keap1-Nrf2 PPI inhibition.

The development of natural peptides as direct Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid2-related factor 2 (Nrf2) protein-protein interaction (PPI) inhibitors for antioxidant and anti-ferroptotic purposes has attracted increasing interest from chemists. (RAS) is a widely used traditional Chinese medicine with antioxidant capability. However, few studies have screened Keap1-Nrf2 PPI inhibitory RAS peptides (RASPs).

Antioxidant mechanisms and products of four 4',5,7-trihydroxyflavonoids with different structural types.

4',5,7-OHs are common substituents of natural flavonoids, a type of effective phenolic antioxidant. However, the antioxidant processes between 4',5,7-trihydroxyflavonoids with different structural types have not been compared systematically, and the antioxidant products are challenging to determine. This study compared four 4',5,7-trihydroxyflavonoids, including apigenin, genistein, kaempferol, and naringenin.

Linkage and Stereochemistry Characters of Phenolic Antioxidant Product Formation.

The present study developed a smart and novel strategy to elucidate the linkage and stereochemistry characters during phenolic antioxidant product formation. A series of phenolic isomers or analogues were treated with 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide radical, to create 16 antioxidant dimerization reactions in aqueous solution. The products were rapidly identified by ultraperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass-spectrometry.

Phytophenol Dimerization Reaction: From Basic Rules to Diastereoselectivity and Beyond.

Phytophenol dimerization, which is a radical-mediated coupling reaction, plays a critical role in many fields, including lignin biosynthesis. To understand the reaction, 2,2-diphenyl-1-picrylhydrazyl radical was used to initiate a series of phytophenol dimerization reactions in methanol. The products were identified using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-ESI-Q-TOF-MS/MS) analysis in situ.

Comparison of Ferroptosis-Inhibitory Mechanisms between Ferrostatin-1 and Dietary Stilbenes (Piceatannol and Astringin).

Synthetic arylamines and dietary phytophenolics could inhibit ferroptosis, a recently discovered regulated cell death process. However, no study indicates whether their inhibitory mechanisms are inherently different. Herein, the ferroptosis-inhibitory mechanisms of selected ferrostatin-1 (Fer-1) and two dietary stilbenes (piceatannol and astringin) were compared.

Structure-activity relationship and mechanism of four monostilbenes with respect to ferroptosis inhibition.

Erastin-treated bone marrow-derived mesenchymal stem cells (bmMSCs) were prepared and used to compare the ferroptosis inhibitory bioactivities of four monostilbenes, including rhapontigenin (1a), isorhapontigenin (1b), piceatannol-3'--glucoside (1c), and rhapontin (1d). Their relative levels were 1c ≈ 1b > 1a ≈ 1d in 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3,4-diaza--indacene-3-undecanoic acid (C11-BODIPY), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and flow cytometric assays. The comparison highlighted two 4'-OH-containing monostilbenes (1c and 1b) in ferroptosis inhibitory bioactivity.

Comparative Analysis of Radical Adduct Formation (RAF) Products and Antioxidant Pathways between Myricetin-3--Galactoside and Myricetin Aglycone.

The biological process, 3--galactosylation, is important in plant cells. To understand the mechanism of the reduction of flavonol antioxidative activity by 3--galactosylation, myricetin-3--galactoside (M3OGa) and myricetin aglycone were each incubated with 2 mol α,α-diphenyl-β-picrylhydrazyl radical (DPPH) and subsequently comparatively analyzed for radical adduct formation (RAF) products using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS) technology. The analyses revealed that M3OGa afforded an M3OGa-DPPH adduct (/ 873.

3',8″-Dimerization Enhances the Antioxidant Capacity of Flavonoids: Evidence from Acacetin and Isoginkgetin.

To probe the effect of 3',8″-dimerization on antioxidant flavonoids, acacetin and its 3',8″-dimer isoginkgetin were comparatively analyzed using three antioxidant assays, namely, the O scavenging assay, the Cu reducing assay, and the 2,2'-azino bis(3-ethylbenzothiazolin-6-sulfonic acid) radical scavenging assay. In these assays, acacetin had consistently higher IC values than isoginkgetin. Subsequently, the acacetin was incubated with 4-methoxy-2,2,6,6-tetramethylpiperidine-1-oxy radicals (4-methoxy-TEMPO) and then analyzed by ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-ESI-Q-TOF-MS) technology.

Antioxidant Mechanisms of Echinatin and Licochalcone A.

Echinatin and its 1,1-dimethyl-2-propenyl derivative licochalcone A are two chalcones found in the Chinese herbal medicine . First, their antioxidant mechanisms were investigated using four sets of colorimetric measurements in this study. Three sets were performed in aqueous solution, namely Cu-reduction, Fe-reduction, and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•)-scavenging measurements, while 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•)-scavenging colorimetric measurements were conducted in methanol solution.

Dual Effect of Glucuronidation of a Pyrogallol-Type Phytophenol Antioxidant: A Comparison between Scutellarein and Scutellarin.

To explore whether and how glucuronidation affects pyrogallol-type phytophenols, scutellarein and scutellarin (scutellarein-7--glucuronide) were comparatively investigated using a set of antioxidant analyses, including spectrophotometric analysis, UV-vis spectra analysis, and ultra-performance liquid chromatography coupled with electrospray ionization-quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) analysis. In spectrophotometric analyses of the scavenging of 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radicals (PTIO) and the reduction of Cu ions, scutellarein showed lower IC values than scutellarin. However, in O₂-scavenging spectrophotometric analysis, scutellarein showed higher IC value than scutellarin.

A Null -Ring Improves the Antioxidant Levels of Flavonol: A Comparative Study between Galangin and 3,5,7-Trihydroxychromone.

To clarify the role of the -ring in antioxidant flavonols, we performed a comparative study between galangin with a null -ring and 3,5,7-trihydroxychromone without a -ring using five spectrophotometric assays, namely, O₂-scavenging, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH)-scavenging, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide radical-scavenging, 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) radical-scavenging, and Fe-reducing activity. The DPPH-scavenging reaction products of these assays were further analyzed by ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) technology. In the five spectrophotometric assays, galangin and 3,5,7-trihydroxychromone dose-dependently increased their radical-scavenging (or Fe-reducing) percentages.