A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity
Aldehyde dehydrogenases (ALDHs) are the major enzyme superfamily for the aldehyde metabolism. Since the ALDH polymorphism leads to the accumulation of acetaldehyde, we considered that the enhancement of the liver ALDH activity by certain food ingredients could help prevent alcohol-induced chronic di...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/3/1762 |
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| author | Yujia Liu Takumi Myojin Kexin Li Ayuki Kurita Masayuki Seto Ayano Motoyama Xiaoyang Liu Ayano Satoh Shintaro Munemasa Yoshiyuki Murata Toshiyuki Nakamura Yoshimasa Nakamura |
| author_facet | Yujia Liu Takumi Myojin Kexin Li Ayuki Kurita Masayuki Seto Ayano Motoyama Xiaoyang Liu Ayano Satoh Shintaro Munemasa Yoshiyuki Murata Toshiyuki Nakamura Yoshimasa Nakamura |
| author_sort | Yujia Liu |
| collection | DOAJ |
| description | Aldehyde dehydrogenases (ALDHs) are the major enzyme superfamily for the aldehyde metabolism. Since the ALDH polymorphism leads to the accumulation of acetaldehyde, we considered that the enhancement of the liver ALDH activity by certain food ingredients could help prevent alcohol-induced chronic diseases. Here, we evaluated the modulating effects of 3-hydroxyphenylacetic acid (OPAC), the major metabolite of quercetin glycosides, on the ALDH activity and acetaldehyde-induced cytotoxicity in the cultured cell models. OPAC significantly enhanced the total ALDH activity not only in mouse hepatoma Hepa1c1c7 cells, but also in human hepatoma HepG2 cells. OPAC significantly increased not only the nuclear level of aryl hydrocarbon receptor (AhR), but also the AhR-dependent reporter gene expression, though not the nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent one. The pretreatment of OPAC at the concentration required for the ALDH upregulation completely inhibited the acetaldehyde-induced cytotoxicity. Silencing AhR impaired the resistant effect of OPAC against acetaldehyde. These results strongly suggested that OPAC protects the cells from the acetaldehyde-induced cytotoxicity, mainly through the AhR-dependent and Nrf2-independent enhancement of the total ALDH activity. Our findings suggest that OPAC has a protective potential in hepatocyte models and could offer a new preventive possibility of quercetin glycosides for targeting alcohol-induced chronic diseases. |
| first_indexed | 2024-03-09T23:44:58Z |
| format | Article |
| id | doaj.art-a148f91ad4a141b58d34a43d72e2a96e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:44:58Z |
| publishDate | 2022-02-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a148f91ad4a141b58d34a43d72e2a96e2023-11-23T16:46:11ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01233176210.3390/ijms23031762A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase ActivityYujia Liu0Takumi Myojin1Kexin Li2Ayuki Kurita3Masayuki Seto4Ayano Motoyama5Xiaoyang Liu6Ayano Satoh7Shintaro Munemasa8Yoshiyuki Murata9Toshiyuki Nakamura10Yoshimasa Nakamura11School of Biological Engineering, Dalian Polytechnic University, Dalian 116034, ChinaGraduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, JapanSchool of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, ChinaGraduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, JapanGraduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, JapanGraduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, JapanSchool of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, ChinaGraduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, JapanGraduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, JapanGraduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, JapanGraduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, JapanGraduate School of Environmental and Life Science, Okayama University, Okayama 700-8530, JapanAldehyde dehydrogenases (ALDHs) are the major enzyme superfamily for the aldehyde metabolism. Since the ALDH polymorphism leads to the accumulation of acetaldehyde, we considered that the enhancement of the liver ALDH activity by certain food ingredients could help prevent alcohol-induced chronic diseases. Here, we evaluated the modulating effects of 3-hydroxyphenylacetic acid (OPAC), the major metabolite of quercetin glycosides, on the ALDH activity and acetaldehyde-induced cytotoxicity in the cultured cell models. OPAC significantly enhanced the total ALDH activity not only in mouse hepatoma Hepa1c1c7 cells, but also in human hepatoma HepG2 cells. OPAC significantly increased not only the nuclear level of aryl hydrocarbon receptor (AhR), but also the AhR-dependent reporter gene expression, though not the nuclear factor erythroid-2-related factor 2 (Nrf2)-dependent one. The pretreatment of OPAC at the concentration required for the ALDH upregulation completely inhibited the acetaldehyde-induced cytotoxicity. Silencing AhR impaired the resistant effect of OPAC against acetaldehyde. These results strongly suggested that OPAC protects the cells from the acetaldehyde-induced cytotoxicity, mainly through the AhR-dependent and Nrf2-independent enhancement of the total ALDH activity. Our findings suggest that OPAC has a protective potential in hepatocyte models and could offer a new preventive possibility of quercetin glycosides for targeting alcohol-induced chronic diseases.https://www.mdpi.com/1422-0067/23/3/17623-hydroxyphenylacetic acidaldehyde dehydrogenasequercetin metabolitesaryl hydrocarbon receptoracetaldehyde |
| spellingShingle | Yujia Liu Takumi Myojin Kexin Li Ayuki Kurita Masayuki Seto Ayano Motoyama Xiaoyang Liu Ayano Satoh Shintaro Munemasa Yoshiyuki Murata Toshiyuki Nakamura Yoshimasa Nakamura A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity International Journal of Molecular Sciences 3-hydroxyphenylacetic acid aldehyde dehydrogenase quercetin metabolites aryl hydrocarbon receptor acetaldehyde |
| title | A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity |
| title_full | A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity |
| title_fullStr | A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity |
| title_full_unstemmed | A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity |
| title_short | A Major Intestinal Catabolite of Quercetin Glycosides, 3-Hydroxyphenylacetic Acid, Protects the Hepatocytes from the Acetaldehyde-Induced Cytotoxicity through the Enhancement of the Total Aldehyde Dehydrogenase Activity |
| title_sort | major intestinal catabolite of quercetin glycosides 3 hydroxyphenylacetic acid protects the hepatocytes from the acetaldehyde induced cytotoxicity through the enhancement of the total aldehyde dehydrogenase activity |
| topic | 3-hydroxyphenylacetic acid aldehyde dehydrogenase quercetin metabolites aryl hydrocarbon receptor acetaldehyde |
| url | https://www.mdpi.com/1422-0067/23/3/1762 |
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