3-Bromo-4,5-dihydroxybenzaldehyde Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes.

A natural bromophenol found in seaweeds, 3-bromo-4,5-dihydroxybenzaldehyde (BDB), has been shown to possess antioxidant effects. This study aimed to investigate the mechanism by which BDB protects skin cells subjected to oxidative stress. The effect of BDB on the protein and mRNA levels of glutathione-related enzymes and the cell survival of human keratinocytes (HaCaT cells) was investigated. BDB treatment increased the protein and mRNA levels of glutathione synthesizing enzymes and enhanced the production of reduced glutathione in HaCaT cells. Furthermore, BDB activated NF-E2-related factor 2 (Nrf2) and promoted its localization into the nucleus by phosphorylating its up-stream signaling proteins, extracellular signal-regulated kinase and protein kinase B. Thus, BDB increased the production of reduced glutathione and established cellular protection against oxidative stress via an Nrf2-mediated pathway.

Photo-protective effect of sargachromenol against UVB radiation-induced damage through modulating cellular antioxidant systems and apoptosis in human keratinocytes.

The aim of this study was to evaluate the photo-preventive effects of sargachromenol (SC) against ultraviolet B (UVB)-induced oxidative stress in human keratinocytes via assessing the antioxidant properties and underlying molecular mechanisms. SC exhibited a significant scavenging effect on UVB-induced intracellular reactive oxygen species (ROS). SC attenuated UVB-induced oxidative macromolecular damage, including the protein carbonyl content, DNA strand break, and 8-isoprostane level. Furthermore, SC decreased UVB-induced Bax, cleaved caspase-9, and cleaved caspase-3 protein levels, but increased that of Bcl-2, which are well-known key mediators of apoptosis. Moreover, SC increased superoxide dismutase, catalase, and heme oxygenase-1 protein expression. Pre-treatment with SC upregulated the main transcription factor of antioxidant enzymes, erythroid 2-related factor 2 level, which was reduced by UVB irradiation. Extracellular signal-regulated kinase (ERK) and Jun N-terminal kinases (JNK) are involved in the regulation of many cellular events, including apoptosis. SC treatment reversed ERK and JNK activation induced by UVB. Collectively, these data indicate that SC can provide remarkable cytoprotection against the adverse effects of UVB radiation by modulating cellular antioxidant systems, and suggest the potential of developing a medical agent for ROS-induced skin diseases.

Rosmarinic Acid Attenuates Cell Damage against UVB Radiation-Induced Oxidative Stress via Enhancing Antioxidant Effects in Human HaCaT Cells.

This study was designed to investigate the cytoprotective effect of rosmarinic acid (RA) on ultraviolet B (UVB)-induced oxidative stress in HaCaT keratinocytes. RA exerted a significant cytoprotective effect by scavenging intracellular ROS induced by UVB. RA also attenuated UVB-induced oxidative macromolecular damage, including protein carbonyl content, DNA strand breaks, and the level of 8-isoprostane. Furthermore, RA increased the expression and activity of superoxide dismutase, catalase, heme oxygenase-1, and their transcription factor Nrf2, which are decreased by UVB radiation. Collectively, these data indicate that RA can provide substantial cytoprotection against the adverse effects of UVB radiation by modulating cellular antioxidant systems, and has potential to be developed as a medical agent for ROS-induced skin diseases.

Protective Effect of Diphlorethohydroxycarmalol against Ultraviolet B Radiation-Induced DNA Damage by Inducing the Nucleotide Excision Repair System in HaCaT Human Keratinocytes.

We investigated the protective properties of diphlorethohydroxycarmalol (DPHC), a phlorotannin, against ultraviolet B (UVB) radiation-induced cyclobutane pyrimidine dimers (CPDs) in HaCaT human keratinocytes. The nucleotide excision repair (NER) system is the pathway by which cells identify and repair bulky, helix-distorting DNA lesions such as ultraviolet (UV) radiation-induced CPDs and 6-4 photoproducts. CPDs levels were elevated in UVB-exposed cells; however, this increase was reduced by DPHC. Expression levels of xeroderma pigmentosum complementation group C (XPC) and excision repair cross-complementing 1 (ERCC1), which are essential components of the NER pathway, were induced in DPHC-treated cells. Expression of XPC and ERCC1 were reduced following UVB exposure, whereas DPHC treatment partially restored the levels of both proteins. DPHC also increased expression of transcription factor specificity protein 1 (SP1) and sirtuin 1, an up-regulator of XPC, in UVB-exposed cells. DPHC restored binding of the SP1 to the XPC promoter, which is reduced in UVB-exposed cells. These results indicate that DPHC can protect cells against UVB-induced DNA damage by inducing the NER system.

Esculetin induces death of human colon cancer cells via the reactive oxygen species-mediated mitochondrial apoptosis pathway.

The present study investigated the apoptotic effects of esculetin, a coumarin derivative, on the human colon cancer cell line HT-29. Esculetin had cytotoxic effects on HT-29 cells in a dose- and time-dependent manner; treatment with 55 µg/mL esculetin reduced cell viability by 50%. Esculetin induced apoptosis, as evidenced by apoptotic body formation, an increased percentage of cells in sub-G1 phase, and DNA fragmentation. Moreover, esculetin increased mitochondrial membrane depolarization, released cytochrome c into cytosol, and modulated the expression of apoptosis-associated proteins, resulting in reduced expression of B cell lymphoma-2, increased expression of Bcl-2-associated X protein, and activation of caspase-9 and caspase-3. Esculetin induced the formation of reactive oxygen species; however, treatment with an antioxidant reduced the apoptotic cell death induced by esculetin treatment. In addition, esculetin activated mitogen-activated protein kinases and specific inhibitors of these kinases abrogated the reduction in cell viability induced by esculetin treatment.