Ginsenoside Rg3 Attenuates TNF-α-Induced Damage in Chondrocytes through Regulating SIRT1-Mediated Anti-Apoptotic and Anti-Inflammatory Mechanisms
The upregulation of tumor necrosis factor-alpha (TNF-α) is a common event in arthritis, and the subsequent signaling cascade that leads to tissue damage has become the research focus. To explore a potential therapeutic strategy to prevent cartilage degradation, we tested the effect of ginsenoside Rg...
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MDPI AG
2021-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/12/1972 |
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| author | Ching-Hou Ma Wan-Ching Chou Chin-Hsien Wu I-Ming Jou Yuan-Kun Tu Pei-Ling Hsieh Kun-Ling Tsai |
| author_facet | Ching-Hou Ma Wan-Ching Chou Chin-Hsien Wu I-Ming Jou Yuan-Kun Tu Pei-Ling Hsieh Kun-Ling Tsai |
| author_sort | Ching-Hou Ma |
| collection | DOAJ |
| description | The upregulation of tumor necrosis factor-alpha (TNF-α) is a common event in arthritis, and the subsequent signaling cascade that leads to tissue damage has become the research focus. To explore a potential therapeutic strategy to prevent cartilage degradation, we tested the effect of ginsenoside Rg3, a bioactive component of <i>Panax ginseng</i>, on TNF-α-stimulated chondrocytes.TC28a2 Human Chondrocytes were treated with TNF-α to induce damage of chondrocytes. SIRT1 and PGC-1a expression levels were investigated by Western blotting assay. Mitochondrial SIRT3 and acetylated Cyclophilin D (CypD) were investigated using mitochondrial isolation. The mitochondrial mass number and mitochondrial DNA copy were studied for mitochondrial biogenesis. MitoSOX and JC-1 were used for the investigation of mitochondrial ROS and membrane potential. Apoptotic markers, pro-inflammatory events were also tested to prove the protective effects of Rg3. We showed Rg3 reversed the TNF-α-inhibited SIRT1 expression. Moreover, the activation of the SIRT1/PGC-1α/SIRT3 pathway by Rg3 suppressed the TNF-α-induced acetylation of CypD, resulting in less mitochondrial dysfunction and accumulation of reactive oxygen species (ROS). Additionally, we demonstrated that the reduction of ROS ameliorated the TNF-α-elicited apoptosis. Furthermore, the Rg3-reverted SIRT1/PGC-1α/SIRT3 activation mediated the repression of p38 MAPK, which downregulated the NF-κB translocation in the TNF-α-treated cells. Our results revealed that administration of Rg3 diminished the production of interleukin 8 (IL-8) and matrix metallopeptidase 9 (MMP-9) in chondrocytes via SIRT1/PGC-1α/SIRT3/p38 MAPK/NF-κB signaling in response to TNF-α stimulation. Taken together, we showed that Rg3 may serve as an adjunct therapy for patients with arthritis. |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T04:38:50Z |
| publishDate | 2021-12-01 |
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| spelling | doaj.art-a7c7f5fcfef44174b65a084ccdbc44cf2023-11-23T03:33:43ZengMDPI AGAntioxidants2076-39212021-12-011012197210.3390/antiox10121972Ginsenoside Rg3 Attenuates TNF-α-Induced Damage in Chondrocytes through Regulating SIRT1-Mediated Anti-Apoptotic and Anti-Inflammatory MechanismsChing-Hou Ma0Wan-Ching Chou1Chin-Hsien Wu2I-Ming Jou3Yuan-Kun Tu4Pei-Ling Hsieh5Kun-Ling Tsai6Department of Orthopedics, E-Da Hospital, Kaohsiung City 824, TaiwanDepartment of Orthopedics, E-Da Hospital, Kaohsiung City 824, TaiwanDepartment of Orthopedics, E-Da Hospital, Kaohsiung City 824, TaiwanDepartment of Orthopedics, E-Da Hospital, Kaohsiung City 824, TaiwanDepartment of Orthopedics, E-Da Hospital, Kaohsiung City 824, TaiwanDepartment of Anatomy, School of Medicine, China Medical University, Taichung 404, TaiwanDepartment of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan 701, TaiwanThe upregulation of tumor necrosis factor-alpha (TNF-α) is a common event in arthritis, and the subsequent signaling cascade that leads to tissue damage has become the research focus. To explore a potential therapeutic strategy to prevent cartilage degradation, we tested the effect of ginsenoside Rg3, a bioactive component of <i>Panax ginseng</i>, on TNF-α-stimulated chondrocytes.TC28a2 Human Chondrocytes were treated with TNF-α to induce damage of chondrocytes. SIRT1 and PGC-1a expression levels were investigated by Western blotting assay. Mitochondrial SIRT3 and acetylated Cyclophilin D (CypD) were investigated using mitochondrial isolation. The mitochondrial mass number and mitochondrial DNA copy were studied for mitochondrial biogenesis. MitoSOX and JC-1 were used for the investigation of mitochondrial ROS and membrane potential. Apoptotic markers, pro-inflammatory events were also tested to prove the protective effects of Rg3. We showed Rg3 reversed the TNF-α-inhibited SIRT1 expression. Moreover, the activation of the SIRT1/PGC-1α/SIRT3 pathway by Rg3 suppressed the TNF-α-induced acetylation of CypD, resulting in less mitochondrial dysfunction and accumulation of reactive oxygen species (ROS). Additionally, we demonstrated that the reduction of ROS ameliorated the TNF-α-elicited apoptosis. Furthermore, the Rg3-reverted SIRT1/PGC-1α/SIRT3 activation mediated the repression of p38 MAPK, which downregulated the NF-κB translocation in the TNF-α-treated cells. Our results revealed that administration of Rg3 diminished the production of interleukin 8 (IL-8) and matrix metallopeptidase 9 (MMP-9) in chondrocytes via SIRT1/PGC-1α/SIRT3/p38 MAPK/NF-κB signaling in response to TNF-α stimulation. Taken together, we showed that Rg3 may serve as an adjunct therapy for patients with arthritis.https://www.mdpi.com/2076-3921/10/12/1972ginsenoside Rg3chondrocytesSIRT1apoptosisinflammation |
| spellingShingle | Ching-Hou Ma Wan-Ching Chou Chin-Hsien Wu I-Ming Jou Yuan-Kun Tu Pei-Ling Hsieh Kun-Ling Tsai Ginsenoside Rg3 Attenuates TNF-α-Induced Damage in Chondrocytes through Regulating SIRT1-Mediated Anti-Apoptotic and Anti-Inflammatory Mechanisms Antioxidants ginsenoside Rg3 chondrocytes SIRT1 apoptosis inflammation |
| title | Ginsenoside Rg3 Attenuates TNF-α-Induced Damage in Chondrocytes through Regulating SIRT1-Mediated Anti-Apoptotic and Anti-Inflammatory Mechanisms |
| title_full | Ginsenoside Rg3 Attenuates TNF-α-Induced Damage in Chondrocytes through Regulating SIRT1-Mediated Anti-Apoptotic and Anti-Inflammatory Mechanisms |
| title_fullStr | Ginsenoside Rg3 Attenuates TNF-α-Induced Damage in Chondrocytes through Regulating SIRT1-Mediated Anti-Apoptotic and Anti-Inflammatory Mechanisms |
| title_full_unstemmed | Ginsenoside Rg3 Attenuates TNF-α-Induced Damage in Chondrocytes through Regulating SIRT1-Mediated Anti-Apoptotic and Anti-Inflammatory Mechanisms |
| title_short | Ginsenoside Rg3 Attenuates TNF-α-Induced Damage in Chondrocytes through Regulating SIRT1-Mediated Anti-Apoptotic and Anti-Inflammatory Mechanisms |
| title_sort | ginsenoside rg3 attenuates tnf α induced damage in chondrocytes through regulating sirt1 mediated anti apoptotic and anti inflammatory mechanisms |
| topic | ginsenoside Rg3 chondrocytes SIRT1 apoptosis inflammation |
| url | https://www.mdpi.com/2076-3921/10/12/1972 |
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