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Acute antioxidant and cytoprotective effects of sulforaphane in brain endothelial cells and astrocytes during inflammation and excitotoxicity.

ABSTRACT: Sulforaphane (SFN), a bioactive phytochemical isothiocyanate, has a wide spectrum of cytoprotective effects that involve induction of antioxidant genes. Nongenomic antioxidant effects of SFN have not been investigated. Brain oxidative stress during inflammation and excitotoxicity leads to neurovascular injury. We tested the hypothesis that SNF exhibits acute antioxidant effects and prevents neurovascular injury during oxidative stress. In primary cultures of cerebral microvascular endothelial cells (CMVEC) and cortical astrocytes from the newborn pig brain, a pro-inflammatory cytokine TNF-α and an excitotoxic glutamate elevate reactive oxygen species (ROS) and cause cell death by apoptosis. Nox4 NADPH oxidase is the main Nox isoform in CMVEC and cortical astrocytes that is acutely activated by TNF-α and glutamate leading to ROS-mediated cell death by apoptosis. The Nox4 inhibitor GKT137831 blocked NADPH oxidase activity and overall ROS elevation, and prevented apoptosis of CMVEC and astrocytes exposed to TNF-α and glutamate, supporting the leading role of Nox4 in the neurovascular injury. Synthetic SFN (10^-11 -10^-6 mol/L) inhibited NADPH oxidase activity and reduced overall ROS production in CMVEC and astrocytes within 1-hour exposure to TNF-α and glutamate. Furthermore, in the presence of SFN, the ability of TNF-α and glutamate to produce apoptosis in CMVEC and cortical astrocytes was completely prevented. Overall, SFN at low concentrations exhibits antioxidant and antiapoptotic effects in cerebral endothelial cells and cortical astrocytes via a via a nongenomic mechanism that involves inhibition of Nox4 NADPH oxidase activity. SFN may prevent cerebrovascular injury during brain oxidative stress caused by inflammation and glutamate excitotoxicity.

SUBMITTER: Liu J

PROVIDER: S-EPMC7383090 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Tibetan tea (Kangzhuan) is an essential beverage of the Tibetan people. In this study, a lyophilized aqueous extract of Tibetan tea (LATT) was prepared and analyzed by HPLC. The results suggested that there were at least five phenolic components, including gallic acid, and four catechins (i.e., (+)-catechin, (-)-catechin gallate (CG), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate). Gallic acid, the four catechins, and LATT were then comparatively investigated by four antioxidant assays: ferric reducing antioxidant power, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•) scavenging, 1,1-diphenyl-2-picryl-hydrazl radical scavenging, and 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) radical scavenging assays. In these assays, LATT, along with the five phenolic components, increased their antioxidant effects in a concentration-dependent manner; however, the half maximal scavenging concentrations of ECG were always lower than those of CG. Gallic acid and the four catechins were also suggested to chelate Fe2+ based on UV-visible spectral analysis. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) analysis suggested that, when mixed with PTIO•, the five phenolic components could yield two types of radical adduct formation (RAF) products (i.e., tea phenolic dimers and tea phenolic-PTIO• adducts). In a flow cytometry assay, (+)-catechin and LATT was observed to have a cytoprotective effect towards oxidative-stressed bone marrow-derived mesenchymal stem cells. Based on this evidence, we concluded that LATT possesses antioxidative or cytoprotective properties. These effects may mainly be attributed to the presence of phenolic components, including gallic acid and the four catechins. These phenolic components may undergo electron transfer, H⁺-transfer, and Fe2+-chelating pathways to exhibit antioxidative or cytoprotective effects. In these effects, two diastereoisomeric CG and ECG showed differences to which a steric effect from the 2-carbon may contribute. Phenolic component decay may cause RAF in the antioxidant process.

Project description:BackgroundPyrola decorata H. Andres, is exclusively distributed in China and a source of traditional Chinese herbal medicine Luxiancao for more than 2000 years. Here, we evaluated the antioxidant and cytoprotective effects of P. decorata and its five phenolic components (protocatechuic acid, gallic acid, hyperoside, 2''-O-galloylhyperin, and quercetin), and discussed their antioxidant chemistry.MethodsA lyophilized aqueous extract of P. decorata (LAEP) was prepared and analyzed with high-performance liquid chromatography (HPLC). LAEP and its five phenolic components were comparatively investigated using five antioxidant assays, including ferric-reducing antioxidant power, cupric ion-reducing antioxidant capacity, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide radical (PTIO•)-scavenging, 1,1-diphenyl-2-picryl-hydrazl radical (DPPH•)-scavenging, and 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) radical (ABTS+•)-scavenging activities. The reaction products of the five phenolic components with 4-methoxy-2,2,6,6-tetramethylpiperidine-1-oxyl radical (4-methoxy-TEMPO•) were determined with ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) analysis. LAEP and its five phenolic components were incubated with bone marrow-derived mesenchymal stem cells (bmMSCs) subjected to oxidative stress to demonstrate their cytoprotective effects with a flow cytometry assay.ResultsIn the five antioxidant assays, LAEP and its five phenolic components dose-dependently increased the radical-scavenging (or reducing power) activities. However, the IC50 values of hyperoside were consistently higher than those of 2''-O-galloylhyperin. UPLC-ESI-Q-TOF-MS/MS analysis results indicated that the five phenolics could yield dimer products in the presence of 4-methoxy-TEMPO• via the radical adduct formation (RAF) pathway. Flow cytometry assay results confirmed the cytoprotective activity of LAEP and its five phenolic components toward stressed bmMSCs. In particular, 2''-O-galloylhyperin could more effectively reduce the percentage of damaged bmMSCs than hyperoside.ConclusionLAEP and its five phenolic components may undergo redox-based pathways (such as electron transfer and H+ transfer) and covalent-based pathway (i.e., RAF) to exhibit antioxidant activity. One consequence of RAF is the generation of phenolic-phenolic dimer. In both organic and aqueous media, 2''-O-galloylhyperin exhibited higher redox-based antioxidant levels (or cytoprotective levels) than those with hyperoside. The differences could be attributed to 2''-O-galloylation reaction.

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Acute antioxidant and cytoprotective effects of sulforaphane in brain endothelial cells and astrocytes during inflammation and excitotoxicity.

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