Antioxidant Activities and Mechanisms of Tomentosin in Human Keratinocytes
Tomentosin, one of natural sesquiterpene lactones sourced from <i>Inula viscosa</i> L., exerts therapeutic effects in various cell types. Here, we investigated the antioxidant activities and the underlying action mechanisms of tomentosin in HaCaT cells (a human keratinocyte cell line). S...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/5/990 |
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| author | Seyoung Yang See-Hyoung Park Sae Woong Oh Kitae Kwon Eunbi Yu Chae Won Lee Youn Kyoung Son Changmu Kim Byoung-Hee Lee Jae Youl Cho Youn-Jung Kim Jongsung Lee |
| author_facet | Seyoung Yang See-Hyoung Park Sae Woong Oh Kitae Kwon Eunbi Yu Chae Won Lee Youn Kyoung Son Changmu Kim Byoung-Hee Lee Jae Youl Cho Youn-Jung Kim Jongsung Lee |
| author_sort | Seyoung Yang |
| collection | DOAJ |
| description | Tomentosin, one of natural sesquiterpene lactones sourced from <i>Inula viscosa</i> L., exerts therapeutic effects in various cell types. Here, we investigated the antioxidant activities and the underlying action mechanisms of tomentosin in HaCaT cells (a human keratinocyte cell line). Specifically, we examined the involvement of tomentosin in aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Treatment with tomentosin for up to 60 min triggered the production of reactive oxygen species (ROS), whereas treatment for 4 h or longer decreased ROS production. Tomentosin treatment also induced the nuclear translocation of Nrf2 and upregulated the expression of Nrf2 and its target genes. These data indicate that tomentosin induces ROS production at an early stage which activates the Nrf2 pathway by disrupting the Nrf2–Keap1 complex. However, at a later stage, ROS levels were reduced by tomentosin-induced upregulation of antioxidant genes. In addition, tomentosin induced the phosphorylation of mitogen-activated protein kinases (MAPKs) including p38 MAPK and c-Jun <i>N</i>-terminal kinase (JNK). SB203580 (a p38 MAPK inhibitor) and SP600125 (a JNK inhibitor) attenuated the tomentosin-induced phosphorylation of Nrf2, suggesting that JNK and p38 MAPK signaling pathways can contribute to the tomentosin-induced Nrf2 activation through phosphorylation of Nrf2. Furthermore, <i>N</i>-acetyl-<i><sub>L</sub></i>-cysteine (NAC) treatment blocked both tomentosin-induced production of ROS and the nuclear translocation of Nrf2. These data suggest that tomentosin-induced Nrf2 signaling is mediated both by tomentosin-induced ROS production and the activation of p38 MAPK and JNK. Moreover, tomentosin inhibited the AhR signaling pathway, as evidenced by the suppression of xenobiotic-response element (XRE) reporter activity and the translocation of AhR into nucleus induced by urban pollutants, especially benzo[a]pyrene. These findings suggest that tomentosin can ameliorate skin damage induced by environmental pollutants. |
| first_indexed | 2024-03-10T03:25:02Z |
| format | Article |
| id | doaj.art-0c6cd21ea71741a1b1c43f130cff6daa |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T03:25:02Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-0c6cd21ea71741a1b1c43f130cff6daa2023-11-23T09:52:45ZengMDPI AGAntioxidants2076-39212022-05-0111599010.3390/antiox11050990Antioxidant Activities and Mechanisms of Tomentosin in Human KeratinocytesSeyoung Yang0See-Hyoung Park1Sae Woong Oh2Kitae Kwon3Eunbi Yu4Chae Won Lee5Youn Kyoung Son6Changmu Kim7Byoung-Hee Lee8Jae Youl Cho9Youn-Jung Kim10Jongsung Lee11Molecular Dermatology Laboratory, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City 16419, Gyunggi Do, KoreaDepartment of Bio and Chemical Engineering, Hongik University, Sejong City 30016, KoreaMolecular Dermatology Laboratory, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City 16419, Gyunggi Do, KoreaMolecular Dermatology Laboratory, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City 16419, Gyunggi Do, KoreaMolecular Dermatology Laboratory, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City 16419, Gyunggi Do, KoreaNational Institute of Biological Resources, Environmental Research Complex, Incheon 22689, KoreaNational Institute of Biological Resources, Environmental Research Complex, Incheon 22689, KoreaNational Institute of Biological Resources, Environmental Research Complex, Incheon 22689, KoreaNational Institute of Biological Resources, Environmental Research Complex, Incheon 22689, KoreaMolecular Immunology Laboratory, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City 16419, Gyunggi Do, KoreaDepartment of Marine Sciences, Incheon National University, Incheon 22012, KoreaMolecular Dermatology Laboratory, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City 16419, Gyunggi Do, KoreaTomentosin, one of natural sesquiterpene lactones sourced from <i>Inula viscosa</i> L., exerts therapeutic effects in various cell types. Here, we investigated the antioxidant activities and the underlying action mechanisms of tomentosin in HaCaT cells (a human keratinocyte cell line). Specifically, we examined the involvement of tomentosin in aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Treatment with tomentosin for up to 60 min triggered the production of reactive oxygen species (ROS), whereas treatment for 4 h or longer decreased ROS production. Tomentosin treatment also induced the nuclear translocation of Nrf2 and upregulated the expression of Nrf2 and its target genes. These data indicate that tomentosin induces ROS production at an early stage which activates the Nrf2 pathway by disrupting the Nrf2–Keap1 complex. However, at a later stage, ROS levels were reduced by tomentosin-induced upregulation of antioxidant genes. In addition, tomentosin induced the phosphorylation of mitogen-activated protein kinases (MAPKs) including p38 MAPK and c-Jun <i>N</i>-terminal kinase (JNK). SB203580 (a p38 MAPK inhibitor) and SP600125 (a JNK inhibitor) attenuated the tomentosin-induced phosphorylation of Nrf2, suggesting that JNK and p38 MAPK signaling pathways can contribute to the tomentosin-induced Nrf2 activation through phosphorylation of Nrf2. Furthermore, <i>N</i>-acetyl-<i><sub>L</sub></i>-cysteine (NAC) treatment blocked both tomentosin-induced production of ROS and the nuclear translocation of Nrf2. These data suggest that tomentosin-induced Nrf2 signaling is mediated both by tomentosin-induced ROS production and the activation of p38 MAPK and JNK. Moreover, tomentosin inhibited the AhR signaling pathway, as evidenced by the suppression of xenobiotic-response element (XRE) reporter activity and the translocation of AhR into nucleus induced by urban pollutants, especially benzo[a]pyrene. These findings suggest that tomentosin can ameliorate skin damage induced by environmental pollutants.https://www.mdpi.com/2076-3921/11/5/990tomentosinhuman keratinocytesROSp38 MAPKJNKNrf2 |
| spellingShingle | Seyoung Yang See-Hyoung Park Sae Woong Oh Kitae Kwon Eunbi Yu Chae Won Lee Youn Kyoung Son Changmu Kim Byoung-Hee Lee Jae Youl Cho Youn-Jung Kim Jongsung Lee Antioxidant Activities and Mechanisms of Tomentosin in Human Keratinocytes Antioxidants tomentosin human keratinocytes ROS p38 MAPK JNK Nrf2 |
| title | Antioxidant Activities and Mechanisms of Tomentosin in Human Keratinocytes |
| title_full | Antioxidant Activities and Mechanisms of Tomentosin in Human Keratinocytes |
| title_fullStr | Antioxidant Activities and Mechanisms of Tomentosin in Human Keratinocytes |
| title_full_unstemmed | Antioxidant Activities and Mechanisms of Tomentosin in Human Keratinocytes |
| title_short | Antioxidant Activities and Mechanisms of Tomentosin in Human Keratinocytes |
| title_sort | antioxidant activities and mechanisms of tomentosin in human keratinocytes |
| topic | tomentosin human keratinocytes ROS p38 MAPK JNK Nrf2 |
| url | https://www.mdpi.com/2076-3921/11/5/990 |
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