Antioxidation and Cytoprotection of Acteoside and Its Derivatives: Comparison and Mechanistic Chemistry

Abstract

The study tried to explore the role of sugar-residues and mechanisms of phenolic phenylpropanoid antioxidants. Acteoside, along with its apioside forsythoside B and rhamnoside poliumoside, were comparatively investigated using various antioxidant assays. In three electron-transfer (ET)-based assays (FRAP, CUPRAC, PTIO•-scavenging at pH 4.5), the relative antioxidant levels roughly ruled as: acteoside >forsythoside B > poliumoside. Such order was also observed in H⁺-transfer-involved PTIO•-scavenging assay at pH 7.4, and in three multiple-pathway-involved radical-scavenging assays, i.e., ABTS⁺•-scavenging, DPPH•-scavenging, and •O₂^--scavenging. In UV-vis spectra, each of them displayed a red-shift at 335→364 nm and two weak peaks (480 and 719 nm), when mixed with Fe²⁺; however, acteoside gave the weakest absorption. In Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) analysis, no radical-adduct-formation (RAF) peak was found. MTT assay revealed that poliumoside exhibited the highest viability of oxidative-stressed bone marrow-derived mesenchymal stem cells. In conclusion, acteoside, forsythoside B, and poliumoside may be involved in multiple-pathways to exert the antioxidant action, including ET, H⁺-transfer, or Fe²⁺-chelating, but not RAF. The ET and H⁺-transfer may be hindered by rhamnosyl and apiosyl moieties; however, the Fe²⁺-chelating potential can be enhanced by two sugar-residues (especially rhamnosyl moiety). The general effect of rhamnosyl and apiosyl moieties is to improve the antioxidant or cytoprotective effects.

Keywords: acteoside; apiosyl; forsythoside B; phenylpropanoid glycosides; poliumoside; rhamnosyl.

Figure 1

The structures (left) and preferential-conformation-based ball-and-stick models (right) of three natural phenylpropanoid glycosides (acteoside, forsythoside B, and poliumoside).

Figure 2

The results of Fe²⁺-chelating reaction of acteoside and its derivatives. (A) UV-vis spectra of the reaction mixture of Fe²⁺ with acteoside; (B) UV-vis spectra of the reaction mixture of Fe²⁺ with forsythoside B; (C) UV-vis spectra of the reaction mixture of Fe²⁺ with poliumoside; (D) The solution appearances.

Figure 3

Flow chart of MTT assay experiment (Bio-Kinetics reader was the product of PE-1420; Bio-Kinetics Corporation, Sioux Center, IA, USA). MTT was at 5 mg/mL (in PBS), and the addition volume was 20 µL. Addition of oxidative reagent was conducted by injection of H₂O₂ (50 μM).