Neuroprotective Effect of Mixed Mushroom Mycelia Extract on Neurotoxicity and Neuroinflammation via Regulation of ROS-Induced Oxidative Stress in PC12 and BV2 Cells
In this study, we investigated the potential of a three-mushroom complex extract (GMK) to inhibit neuronal cell death induced by the activation of AMPA and NMDA receptors following glutamate treatment in NGF-differentiated PC12 neuronal cells. GMK significantly mitigated glutamate-induced excitotoxi...
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2025-06-01
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| author | Sang-Seop Lee Da-Hyun Ko Ga-Young Lee So-Yeon Kim Seung-Yun Han Jong-Yea Park MiNa Park Hyun-Min Kim Ya-El Kim Yung-Choon Yoo |
| author_facet | Sang-Seop Lee Da-Hyun Ko Ga-Young Lee So-Yeon Kim Seung-Yun Han Jong-Yea Park MiNa Park Hyun-Min Kim Ya-El Kim Yung-Choon Yoo |
| author_sort | Sang-Seop Lee |
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| description | In this study, we investigated the potential of a three-mushroom complex extract (GMK) to inhibit neuronal cell death induced by the activation of AMPA and NMDA receptors following glutamate treatment in NGF-differentiated PC12 neuronal cells. GMK significantly mitigated glutamate-induced excitotoxic neuronal apoptosis by reducing the elevated expression of BAX, a critical regulator of apoptosis, and restoring BCL2 levels. These neuroprotective effects were associated with redox regulation, as evidenced by the upregulation of SOD, CAT, and GSH levels, and the downregulation of MDA levels. Mechanistic studies further revealed that GMK effectively scavenged ROS by downregulating NOX1, NOX2, and NOX4, while upregulating NRF1, P62, NRF2, HO1, and NQO1. Additionally, in the same model, GMK treatment increased acetylcholine, choline acetyltransferase, and GABA levels while reducing acetylcholinesterase activity. These effects were also attributed to the regulation of redox balance. Furthermore, we investigated the antioxidant and anti-inflammatory mechanisms of GMK in LPS-stimulated BV2 microglia. GMK inhibited the activation of IκB and MAPK pathways, positively regulated the BCL2/BAX ratio, suppressed TXNIP activity, and upregulated NQO1 and NOX1. In conclusion, GMK improved neuronal excitotoxicity and microglial inflammation through the positive modulation of the redox regulatory system, demonstrating its potential as a natural resource for pharmaceutical applications and functional health foods. |
| format | Article |
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| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-06-01 |
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| series | Cells |
| spelling | doaj-art-6c97b3ff76d3453e9502cfb53ceed7b42025-08-20T03:50:17ZengMDPI AGCells2073-44092025-06-01141397710.3390/cells14130977Neuroprotective Effect of Mixed Mushroom Mycelia Extract on Neurotoxicity and Neuroinflammation via Regulation of ROS-Induced Oxidative Stress in PC12 and BV2 CellsSang-Seop Lee0Da-Hyun Ko1Ga-Young Lee2So-Yeon Kim3Seung-Yun Han4Jong-Yea Park5MiNa Park6Hyun-Min Kim7Ya-El Kim8Yung-Choon Yoo9Department of Microbiology, College of Medicine, Konyang University, Daejeon 32992, Republic of KoreaDepartment of Microbiology, College of Medicine, Konyang University, Daejeon 32992, Republic of KoreaDepartment of Microbiology, College of Medicine, Konyang University, Daejeon 32992, Republic of KoreaDepartment of Microbiology, College of Medicine, Konyang University, Daejeon 32992, Republic of KoreaDepartment of Anatomy, College of Medicine, Konyang University, Daejeon 32992, Republic of KoreaGiunchan Co., Ltd., Cheonan 31035, Republic of KoreaGiunchan Co., Ltd., Cheonan 31035, Republic of KoreaGiunchan Co., Ltd., Cheonan 31035, Republic of KoreaGiunchan Co., Ltd., Cheonan 31035, Republic of KoreaDepartment of Microbiology, College of Medicine, Konyang University, Daejeon 32992, Republic of KoreaIn this study, we investigated the potential of a three-mushroom complex extract (GMK) to inhibit neuronal cell death induced by the activation of AMPA and NMDA receptors following glutamate treatment in NGF-differentiated PC12 neuronal cells. GMK significantly mitigated glutamate-induced excitotoxic neuronal apoptosis by reducing the elevated expression of BAX, a critical regulator of apoptosis, and restoring BCL2 levels. These neuroprotective effects were associated with redox regulation, as evidenced by the upregulation of SOD, CAT, and GSH levels, and the downregulation of MDA levels. Mechanistic studies further revealed that GMK effectively scavenged ROS by downregulating NOX1, NOX2, and NOX4, while upregulating NRF1, P62, NRF2, HO1, and NQO1. Additionally, in the same model, GMK treatment increased acetylcholine, choline acetyltransferase, and GABA levels while reducing acetylcholinesterase activity. These effects were also attributed to the regulation of redox balance. Furthermore, we investigated the antioxidant and anti-inflammatory mechanisms of GMK in LPS-stimulated BV2 microglia. GMK inhibited the activation of IκB and MAPK pathways, positively regulated the BCL2/BAX ratio, suppressed TXNIP activity, and upregulated NQO1 and NOX1. In conclusion, GMK improved neuronal excitotoxicity and microglial inflammation through the positive modulation of the redox regulatory system, demonstrating its potential as a natural resource for pharmaceutical applications and functional health foods.https://www.mdpi.com/2073-4409/14/13/977mushroom mycelial extractexcitotoxicityneuroinflammationPC12 neuronsBV2 microgliaROS |
| spellingShingle | Sang-Seop Lee Da-Hyun Ko Ga-Young Lee So-Yeon Kim Seung-Yun Han Jong-Yea Park MiNa Park Hyun-Min Kim Ya-El Kim Yung-Choon Yoo Neuroprotective Effect of Mixed Mushroom Mycelia Extract on Neurotoxicity and Neuroinflammation via Regulation of ROS-Induced Oxidative Stress in PC12 and BV2 Cells Cells mushroom mycelial extract excitotoxicity neuroinflammation PC12 neurons BV2 microglia ROS |
| title | Neuroprotective Effect of Mixed Mushroom Mycelia Extract on Neurotoxicity and Neuroinflammation via Regulation of ROS-Induced Oxidative Stress in PC12 and BV2 Cells |
| title_full | Neuroprotective Effect of Mixed Mushroom Mycelia Extract on Neurotoxicity and Neuroinflammation via Regulation of ROS-Induced Oxidative Stress in PC12 and BV2 Cells |
| title_fullStr | Neuroprotective Effect of Mixed Mushroom Mycelia Extract on Neurotoxicity and Neuroinflammation via Regulation of ROS-Induced Oxidative Stress in PC12 and BV2 Cells |
| title_full_unstemmed | Neuroprotective Effect of Mixed Mushroom Mycelia Extract on Neurotoxicity and Neuroinflammation via Regulation of ROS-Induced Oxidative Stress in PC12 and BV2 Cells |
| title_short | Neuroprotective Effect of Mixed Mushroom Mycelia Extract on Neurotoxicity and Neuroinflammation via Regulation of ROS-Induced Oxidative Stress in PC12 and BV2 Cells |
| title_sort | neuroprotective effect of mixed mushroom mycelia extract on neurotoxicity and neuroinflammation via regulation of ros induced oxidative stress in pc12 and bv2 cells |
| topic | mushroom mycelial extract excitotoxicity neuroinflammation PC12 neurons BV2 microglia ROS |
| url | https://www.mdpi.com/2073-4409/14/13/977 |
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