23-Hydroxytormentic acid protects human dermal fibroblasts by attenuating UVA-induced oxidative stress.

BACKGROUND: Ultraviolet A (UVA), one of the major components of sunlight, can penetrate the dermal layer of the skin and generate reactive oxygen species (ROS). It causes alterations in the dermal connective tissue and gene expression, inflammation, photoaging, and DNA damage. AIMS: Therefore, the harmful effects of UVA and strategies to reduce it have been consistently investigated. 23-Hydroxytormentic acid (23-HTA) has been demonstrated to improve drug-induced nephrotoxicity and exhibit several free radical scavenging effects with other molecules. Therefore, the aim of this study was to investigate the anti-inflammatory effects and extracellular matrix (ECM) reconstructive activity of 23-HTA in UVA-irradiated normal human dermal fibroblasts (NHDFs). MATERIALS AND METHODS: The antioxidant capacity of 23-HTA was determined by examining its scavenging activities against hydrogen peroxide, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), and diphenylpicrylhydrazyl in vitro. Its effect on cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tertazolium bromide, and 2,7-dichlorofluorescin diacetate was used to investigate intracellular ROS scavenging activity. The mRNA levels of antioxidant enzymes and pro-inflammatory cytokines were detected using quantitative real-time polymerase chain reaction. A senescence-associated ß-galactosidase (SA-ß-gal) staining kit was used to assess senescent cells. RESULTS: 23-HTA showed antioxidant capacity mediated by ROS scavenging and regulation of antioxidant-related gene expression. Further, the SA-ß-gal analysis and mRNA expression of matrix metalloproteinases and type I procollagen suggested that 23-HTA regulates the gene expression of ECM proteins and cellular senescence under UVA-irradiated conditions. CONCLUSION: In conclusion, 23-HTA protects against and attenuates UVA-induced oxidative stress in NHDFs likely via the nuclear factor erythroid-derived 2-like 2 signaling pathway.

Synthesis and Structure Revision of Dimeric Tadalafil Analogue Adulterants in Dietary Supplements.

A number of phosphodiesterase 5 (PDE5) inhibitors approved by authorities have been used successfully in the treatment of erectile dysfunction. These medicines must be prescribed carefully due to their adverse effects, but they and their analogues are being illegally added to dietary supplements. These illegal dietary supplements pose a significant risk to public health. Several dimeric tadalafil analogues have been synthesized for use as reference standards in the inspection of functional foods that are mainly advertised as sexual enhancement products. During the course of this synthesis, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) was proven to be the reagent of choice for amide coupling to produce these dimeric tadalafil analogues. Moreover, the trans-isomer structures tentatively assigned for the isolated dimeric tadalafil analogues (bisprehomotadalafil and bisprecyclopentyltadalafil) found in dietary supplements are now revised to cis-isomer structures.

Protective effects of rosmarinic acid against hydrogen peroxide­induced cellular senescence and the inflammatory response in normal human dermal fibroblasts.

Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that induces numerous cellular events, including cellular senescence and inflammatory responses. Therefore, the aim of this study was to investigate the protective effect of Rosmarinic acid (RA) in H2O2­induced oxidative stress in normal human dermal fibroblasts (NHDFs). Cytotoxicity assays were performed using a water­soluble tetrazolium salt, and senescence­associated ß­galactosidase activity was determined to investigate the proportion of senescent cells. Antioxidant capacities were evaluated via H2O2­scavenging activity, reverse transcription­quantitative polymerase chain reaction, NRF2 luciferase reporter gene activity and intracellular ROS scavenging assays. Cytokine­coded gene expression analysis and nuclear factor­κB luciferase activity were determined to verify the anti­inflammatory effect of RA. As a result, the present study demonstrated that rosmarinic acid inhibited H2O2­induced oxidative stress and inflammatory responses in normal human dermal fibroblasts. Initially, the doses of RA that exerted minimal cytotoxic effects in NHDFs were determined using a cytotoxicity assay. Subsequently, pretreatment with the appropriate doses of RA significantly reversed the H2O2­induced decrease in NHDF cell viability and decreased cellular senescence of NHDFs. In addition, RA inhibited H2O2­induced ROS production in NHDFs, as determined by a ROS scavenging assay. The protective effects of RA were mediated by the inhibition of nuclear factor erythroid­derived 2­like 2, a transcription factor that functions as a key regulator of redox sensitivity. Furthermore, RA suppressed H2O2­induced inflammation in NHDFs and significantly rescued H2O2­induced downregulation of sirtuin 1. RA also inhibited nuclear factor (NF)­κB transcriptional activity and the expression of NF­κB target genes, including tumor necrosis factor­α and interleukin­6, in H2O2­exposed NHDFs. Taken together, these data indicate that RA inhibits H2O2­induced cellular damage in NHDFs.

Protective effect of Arthrospira platensis extracts against ultraviolet B-induced cellular senescence through inhibition of DNA damage and matrix metalloproteinase-1 expression in human dermal fibroblasts.

Ultraviolet (UV) light exposure causes skin photoaging, which is known to be preventable and controllable by application of UV-protective agents. In this study, we demonstrated, for the first time, that the extract of microalgae Arthrospira platensis has a reverse effect on UV-induced photodamage such as loss of cell viability, cellular senescence, DNA damage, and collagen destruction in dermal fibroblasts. Forty-eight extracts were prepared from the cell biomass by controlling culture light conditions, extract solvents, and disruption methods. Then, we analyzed their cytotoxicities using WST-1 assay and separated low and high cytotoxic extracts with normal human dermal fibroblasts (nHDFs). Using the low cytotoxic extracts, we performed UVB protection assay and selected the most effective extract demonstrating protective effect against UVB-induced nHDF damage. Flow cytometric analysis and senescence-associated (SA) ß-galactosidase assay showed that pretreatment with the extract reversed UVB-induced G2/M phase cell cycle arrest and senescence in nHDFs. Furthermore, UVB-induced DNA damage in nHDFs, such as cyclobutane pyrimidine dimer formation, was significantly suppressed by the extract. Further, quantitative real-time PCR experiments revealed that the extract significantly inhibited UVB-induced upregulation of matrix metalloproteinase 1 (MMP1) and MMP3 expression in nHDFs. Therefore, we concluded that the microalgae extract can be a potential anti-photoaging agent.

Erratum to: Extract of Ettlia sp. YC001 Exerts Photoprotective Effects against UVB Irradiation in Normal Human Dermal Fibroblast.

This erratum is being published to correct the errors of the words in the section of Result and the Figure 4B. The words of 'with H2O2' (left column, line 25) in page 781 should be corrected as 'with the extract'. And the Figure 4B in page 780 should be replaced with the below new Figure 4B.

Extract of Ettlia sp. YC001 Exerts Photoprotective Effects against UVB Irradiation in Normal Human Dermal Fibroblasts.

The identification of novel reagents that exert a biological ultraviolet (UV)-protective effect in skin cells represents an important strategy for preventing UV-induced skin aging. To this end, we investigated the potential protective effects of Ettlia sp. YC001 extracts against UV-induced cellular damage in normal human dermal fibroblasts (NHDFs). We generated four different extracts from Ettlia sp. YC001, and found that they exhibit low cytotoxicity in NHDFs. The ethyl acetate extract of Ettlia sp. YC001 markedly decreased UVB-induced cytotoxicity. Additionally, the ethyl acetate extract significantly inhibited the production of hydrogen peroxide-induced reactive oxygen species. Moreover, it inhibited UVB-induced thymine dimers, as confirmed by luciferase assay and thymine dimer dot-blot assay. Thus, the study findings suggest Ettlia sp. YC001 extract as a novel photoprotective reagent on UVB-induced cell dysfunctions in NHDFs.

Pretreatment of Ferulic Acid Protects Human Dermal Fibroblasts against Ultraviolet A Irradiation.

BACKGROUND: Approximately 90%~99% of ultraviolet A (UVA) ray reaches the Earth's surface. The deeply penetrating UVA rays induce the formation of reactive oxygen species (ROS), which results in oxidative stress such as photoproducts, senescence, and cell death. Thus, UVA is considered a primary factor that promotes skin aging. OBJECTIVE: Researchers investigated whether pretreatment with ferulic acid protects human dermal fibroblasts (HDFs) against UVA-induced cell damages. METHODS: HDF proliferation was analyzed using the water-soluble tetrazolium salt assay. Cell cycle distribution and intracellular ROS levels were assessed by flow cytometric analysis. Senescence was evaluated using a senescence-associated ß-galactosidase assay, while Gadd45α promoter activity was analyzed through a luciferase assay. The expression levels of superoxide dismutase 1 (SOD1), catalase (CAT), xeroderma pigmentosum complementation group A and C, matrix metalloproteinase 1 and 3, as well as p21 and p16 were measured using quantitative real-time polymerase chain reaction. RESULTS: Inhibition of proliferation and cell cycle arrest were detected in cells that were irradiated with UVA only. Pretreatment with ferulic acid significantly increased the proliferation and cell cycle progression in HDFs. Moreover, ferulic acid pretreatment produced antioxidant effects such as reduced DCF intensity, and affected SOD1 and CAT mRNA expression. These effects were also demonstrated in the analysis of cell senescence, promoter activity, expression of senescent markers, and DNA repair. CONCLUSION: These results demonstrate that ferulic acid exerts protective effects on UVA-induced cell damages via anti-oxidant and stress-inducible cellular mechanisms in HDFs.

Synthesis of N-Imidoyl and N-Oxoimidoyl Sulfoximines from 1-Alkynes, N-Sulfonyl Azides, and Sulfoximines.

N-Imidoylation of sulfoximines is developed from a Cu-catalyzed three-component reaction from 1-alkynes, N-sulfonyl azides, and sulfoximines in THF at room temperature under air. In addition, N-oxoimidoylation of sulfoximines is accessed from a Cu-catalyzed three-component reaction from 1-alkynes, N-sulfonyl azides, and sulfoximines in THF at room temperature followed by a Cu-catalyzed oxidative reaction at 50 °C under air, producing N-oxoimidoyl sulfoximines.

MicroRNA-1290 promotes asiatic acid­induced apoptosis by decreasing BCL2 protein level in A549 non­small cell lung carcinoma cells.

Asiatic acid, a triterpenoid derived from Centella asiatica, is a putative anticancer agent in several types of cancer cells. Investigations of its biological role in negative regulation of cell growth have focused on the extent of induction of apoptosis in a cell-type-specific manner. In this study, we identified an important regulator of asiatic acid-induced cell death, microRNA (miR)-1290, which sensitizes cells to asiatic acid-induced cytotoxicity and negatively regulates BCL2 expression. Asiatic acid significantly upregulated miR-1290, and asiatic acid-induced cell death was shown to be dependent on miR-1290 activity. Molecular assays demonstrated that BCL2 mRNA is a direct target of miR-1290-mediated RNA interference. The results of functional studies suggest that miR-1290 suppresses cell viability and cell cycle progression. These data provide insight into miR-1290-mediated cellular mechanisms in asiatic acid-treated A549 non-small cell lung carcinoma cells.