Oxymatrine Improves Oxidative Stress-Induced Senescence in HT22 Cells and Mice via the Activation of AMP-Activated Protein Kinase
The accumulation of oxidative stress is one of the important factors causing cellular senescence. Oxymatrine (OM) is a natural quinolizidine alkaloid compound known for its antioxidant effects. This study aimed to investigate the anti-senescence potential of OM through oxidative stress-induced in vi...
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MDPI AG
2023-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/12/2078 |
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| author | Nagarajan Maharajan Chang-Min Lee Karthikeyan A. Vijayakumar Gwang-Won Cho |
| author_facet | Nagarajan Maharajan Chang-Min Lee Karthikeyan A. Vijayakumar Gwang-Won Cho |
| author_sort | Nagarajan Maharajan |
| collection | DOAJ |
| description | The accumulation of oxidative stress is one of the important factors causing cellular senescence. Oxymatrine (OM) is a natural quinolizidine alkaloid compound known for its antioxidant effects. This study aimed to investigate the anti-senescence potential of OM through oxidative stress-induced in vitro and in vivo models. By treating 600 μM of H<sub>2</sub>O<sub>2</sub> to the HT22 mouse hippocampal neuronal cell line and by administering 150 mg/kg D-galactose to mice, we generated oxidative stress-induced senescence models. After providing 1, 2, and 4 μg/mL of OM to the HT22 mouse cell line and by administering 50 mg/kg OM to mice, we evaluated the enhancing effects. We evaluated different senescence markers, AMPK activity, and autophagy, along with DCFH-DA detection reaction and behavioral tests. In HT22 cells, OM showed a protective effect. OM, by reducing ROS and increasing p-AMPK expression, could potentially reduce oxidative stress-induced senescence. In the D-Gal-induced senescence mouse model, both the brain and heart tissues recovered AMPK activity, resulting in reduced levels of senescence. In neural tissue, to assess neurological recovery, including anxiety symptoms and exploration, we used a behavioral test. We also found that OM decreased the expression level of receptors for advanced glycation end products (RAGE). In heart tissue, we could observe the restoration of AMPK activity, which also increased the activity of autophagy. The results of our study suggest that OM ameliorates oxidative stress-induced senescence through its antioxidant action by restoring AMPK activity. |
| first_indexed | 2024-03-08T21:02:18Z |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-08T21:02:18Z |
| publishDate | 2023-12-01 |
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| series | Antioxidants |
| spelling | doaj.art-2741f81714434906b7b47789da0b69812023-12-22T13:48:27ZengMDPI AGAntioxidants2076-39212023-12-011212207810.3390/antiox12122078Oxymatrine Improves Oxidative Stress-Induced Senescence in HT22 Cells and Mice via the Activation of AMP-Activated Protein KinaseNagarajan Maharajan0Chang-Min Lee1Karthikeyan A. Vijayakumar2Gwang-Won Cho3Department of Biological Science, College of Natural Sciences, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 501759, Republic of KoreaDepartment of Biological Science, College of Natural Sciences, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 501759, Republic of KoreaDepartment of Biological Science, College of Natural Sciences, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 501759, Republic of KoreaDepartment of Biological Science, College of Natural Sciences, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 501759, Republic of KoreaThe accumulation of oxidative stress is one of the important factors causing cellular senescence. Oxymatrine (OM) is a natural quinolizidine alkaloid compound known for its antioxidant effects. This study aimed to investigate the anti-senescence potential of OM through oxidative stress-induced in vitro and in vivo models. By treating 600 μM of H<sub>2</sub>O<sub>2</sub> to the HT22 mouse hippocampal neuronal cell line and by administering 150 mg/kg D-galactose to mice, we generated oxidative stress-induced senescence models. After providing 1, 2, and 4 μg/mL of OM to the HT22 mouse cell line and by administering 50 mg/kg OM to mice, we evaluated the enhancing effects. We evaluated different senescence markers, AMPK activity, and autophagy, along with DCFH-DA detection reaction and behavioral tests. In HT22 cells, OM showed a protective effect. OM, by reducing ROS and increasing p-AMPK expression, could potentially reduce oxidative stress-induced senescence. In the D-Gal-induced senescence mouse model, both the brain and heart tissues recovered AMPK activity, resulting in reduced levels of senescence. In neural tissue, to assess neurological recovery, including anxiety symptoms and exploration, we used a behavioral test. We also found that OM decreased the expression level of receptors for advanced glycation end products (RAGE). In heart tissue, we could observe the restoration of AMPK activity, which also increased the activity of autophagy. The results of our study suggest that OM ameliorates oxidative stress-induced senescence through its antioxidant action by restoring AMPK activity.https://www.mdpi.com/2076-3921/12/12/2078OxymatrineAMPKcellular senescenceoxidative stressautophagy |
| spellingShingle | Nagarajan Maharajan Chang-Min Lee Karthikeyan A. Vijayakumar Gwang-Won Cho Oxymatrine Improves Oxidative Stress-Induced Senescence in HT22 Cells and Mice via the Activation of AMP-Activated Protein Kinase Antioxidants Oxymatrine AMPK cellular senescence oxidative stress autophagy |
| title | Oxymatrine Improves Oxidative Stress-Induced Senescence in HT22 Cells and Mice via the Activation of AMP-Activated Protein Kinase |
| title_full | Oxymatrine Improves Oxidative Stress-Induced Senescence in HT22 Cells and Mice via the Activation of AMP-Activated Protein Kinase |
| title_fullStr | Oxymatrine Improves Oxidative Stress-Induced Senescence in HT22 Cells and Mice via the Activation of AMP-Activated Protein Kinase |
| title_full_unstemmed | Oxymatrine Improves Oxidative Stress-Induced Senescence in HT22 Cells and Mice via the Activation of AMP-Activated Protein Kinase |
| title_short | Oxymatrine Improves Oxidative Stress-Induced Senescence in HT22 Cells and Mice via the Activation of AMP-Activated Protein Kinase |
| title_sort | oxymatrine improves oxidative stress induced senescence in ht22 cells and mice via the activation of amp activated protein kinase |
| topic | Oxymatrine AMPK cellular senescence oxidative stress autophagy |
| url | https://www.mdpi.com/2076-3921/12/12/2078 |
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