Didymin alleviates metabolic dysfunction-associated fatty liver disease (MAFLD) via the stimulation of Sirt1-mediated lipophagy and mitochondrial biogenesis
Abstract Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most prevalent metabolic syndromes worldwide. However, no approved pharmacological treatments are available for MAFLD. Chenpi, one kind of dried peel of citrus fruits, has traditionally been utilized as a...
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-023-04790-4 |
| _version_ | 1797376844114165760 |
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| author | Jing-wen Yang Ying Zou Jun Chen Chen Cui Jia Song Meng-meng Yang Jing Gao Hui-qing Hu Long-qing Xia Li-ming Wang Xiao-yu Lv Li Chen Xin-guo Hou |
| author_facet | Jing-wen Yang Ying Zou Jun Chen Chen Cui Jia Song Meng-meng Yang Jing Gao Hui-qing Hu Long-qing Xia Li-ming Wang Xiao-yu Lv Li Chen Xin-guo Hou |
| author_sort | Jing-wen Yang |
| collection | DOAJ |
| description | Abstract Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most prevalent metabolic syndromes worldwide. However, no approved pharmacological treatments are available for MAFLD. Chenpi, one kind of dried peel of citrus fruits, has traditionally been utilized as a medicinal herb for liver diseases. Didymin is a newly identified oral bioactive dietary flavonoid glycoside derived from Chenpi. In this study, we investigated the therapeutic potential of Didymin as an anti-MAFLD drug and elucidated its underlying mechanisms. Methods High-fat diet (HFD)-induced MAFLD mice and alpha mouse liver 12 (AML12) cells were utilized to evaluate the effects and mechanisms of Didymin in the treatment of MAFLD. Liver weight, serum biochemical parameters, and liver morphology were examined to demonstrate the therapeutic efficacy of Didymin in MAFLD treatment. RNA-seq analysis was performed to identify potential pathways that could be affected by Didymin. The impact of Didymin on Sirt1 was corroborated through western blot, molecular docking analysis, microscale thermophoresis (MST), and deacetylase activity assay. Then, a Sirt1 inhibitor (EX-527) was utilized to confirm that Didymin alleviates MAFLD via Sirt1. Western blot and additional assays were used to investigate the underlying mechanisms. Results Our results suggested that Didymin may possess therapeutic potential against MAFLD in vitro and in vivo. By promoting Sirt1 expression as well as directly binding to and activating Sirt1, Didymin triggers downstream pathways that enhance mitochondrial biogenesis and function while reducing apoptosis and enhancing lipophagy. Conclusions These suggest that Didymin could be a promising medication for MAFLD treatment. Furthermore, its therapeutic effects are mediated by Sirt1. |
| first_indexed | 2024-03-08T19:44:28Z |
| format | Article |
| id | doaj.art-74617f624e434f8e97976e808efa5322 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-03-08T19:44:28Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-74617f624e434f8e97976e808efa53222023-12-24T12:27:55ZengBMCJournal of Translational Medicine1479-58762023-12-0121112110.1186/s12967-023-04790-4Didymin alleviates metabolic dysfunction-associated fatty liver disease (MAFLD) via the stimulation of Sirt1-mediated lipophagy and mitochondrial biogenesisJing-wen Yang0Ying Zou1Jun Chen2Chen Cui3Jia Song4Meng-meng Yang5Jing Gao6Hui-qing Hu7Long-qing Xia8Li-ming Wang9Xiao-yu Lv10Li Chen11Xin-guo Hou12Department of Endocrinology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Endocrinology, The Second Hospital of Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityDepartment of Endocrinology, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong UniversityAbstract Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most prevalent metabolic syndromes worldwide. However, no approved pharmacological treatments are available for MAFLD. Chenpi, one kind of dried peel of citrus fruits, has traditionally been utilized as a medicinal herb for liver diseases. Didymin is a newly identified oral bioactive dietary flavonoid glycoside derived from Chenpi. In this study, we investigated the therapeutic potential of Didymin as an anti-MAFLD drug and elucidated its underlying mechanisms. Methods High-fat diet (HFD)-induced MAFLD mice and alpha mouse liver 12 (AML12) cells were utilized to evaluate the effects and mechanisms of Didymin in the treatment of MAFLD. Liver weight, serum biochemical parameters, and liver morphology were examined to demonstrate the therapeutic efficacy of Didymin in MAFLD treatment. RNA-seq analysis was performed to identify potential pathways that could be affected by Didymin. The impact of Didymin on Sirt1 was corroborated through western blot, molecular docking analysis, microscale thermophoresis (MST), and deacetylase activity assay. Then, a Sirt1 inhibitor (EX-527) was utilized to confirm that Didymin alleviates MAFLD via Sirt1. Western blot and additional assays were used to investigate the underlying mechanisms. Results Our results suggested that Didymin may possess therapeutic potential against MAFLD in vitro and in vivo. By promoting Sirt1 expression as well as directly binding to and activating Sirt1, Didymin triggers downstream pathways that enhance mitochondrial biogenesis and function while reducing apoptosis and enhancing lipophagy. Conclusions These suggest that Didymin could be a promising medication for MAFLD treatment. Furthermore, its therapeutic effects are mediated by Sirt1.https://doi.org/10.1186/s12967-023-04790-4DidyminSirt1MAFLDMitochondrial functionLipophagyApoptosis |
| spellingShingle | Jing-wen Yang Ying Zou Jun Chen Chen Cui Jia Song Meng-meng Yang Jing Gao Hui-qing Hu Long-qing Xia Li-ming Wang Xiao-yu Lv Li Chen Xin-guo Hou Didymin alleviates metabolic dysfunction-associated fatty liver disease (MAFLD) via the stimulation of Sirt1-mediated lipophagy and mitochondrial biogenesis Journal of Translational Medicine Didymin Sirt1 MAFLD Mitochondrial function Lipophagy Apoptosis |
| title | Didymin alleviates metabolic dysfunction-associated fatty liver disease (MAFLD) via the stimulation of Sirt1-mediated lipophagy and mitochondrial biogenesis |
| title_full | Didymin alleviates metabolic dysfunction-associated fatty liver disease (MAFLD) via the stimulation of Sirt1-mediated lipophagy and mitochondrial biogenesis |
| title_fullStr | Didymin alleviates metabolic dysfunction-associated fatty liver disease (MAFLD) via the stimulation of Sirt1-mediated lipophagy and mitochondrial biogenesis |
| title_full_unstemmed | Didymin alleviates metabolic dysfunction-associated fatty liver disease (MAFLD) via the stimulation of Sirt1-mediated lipophagy and mitochondrial biogenesis |
| title_short | Didymin alleviates metabolic dysfunction-associated fatty liver disease (MAFLD) via the stimulation of Sirt1-mediated lipophagy and mitochondrial biogenesis |
| title_sort | didymin alleviates metabolic dysfunction associated fatty liver disease mafld via the stimulation of sirt1 mediated lipophagy and mitochondrial biogenesis |
| topic | Didymin Sirt1 MAFLD Mitochondrial function Lipophagy Apoptosis |
| url | https://doi.org/10.1186/s12967-023-04790-4 |
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