Mitigating effects of Jiawei Chaihu Shugan decoction on necroptosis and inflammation of hippocampal neurons in epileptic mice
Abstract Jiawei Chaihu Shugan decoction (JWCHSGD) is a traditional Chinese medicine well-known for its beneficial effects in treating epilepsy (Xianzheng in ancient Chinese), but the molecular mechanism of its action remains unclear. To investigate the molecular mechanism of JWCHSGD’s prevention of...
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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-025-89275-8 |
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| author | Qin Wang Baijun Qin Han Yu Jiawei Zeng Jingjing Fan Qiong Wu Rong Zeng Haichun Yu Xian Zhang Mingfen Li Yanying Zhou Limei Diao |
| author_facet | Qin Wang Baijun Qin Han Yu Jiawei Zeng Jingjing Fan Qiong Wu Rong Zeng Haichun Yu Xian Zhang Mingfen Li Yanying Zhou Limei Diao |
| author_sort | Qin Wang |
| collection | DOAJ |
| description | Abstract Jiawei Chaihu Shugan decoction (JWCHSGD) is a traditional Chinese medicine well-known for its beneficial effects in treating epilepsy (Xianzheng in ancient Chinese), but the molecular mechanism of its action remains unclear. To investigate the molecular mechanism of JWCHSGD’s prevention of epilepsy-mediated neuron from necroptosis and inflammation via the circRNA-Csnk1g3/Csnk1g3-85aa/ CK1γ3/TNF-α signal pathway. In vitro, murine neuronal HT22 cells were treated in six groups: control, model, carbamazepine, and three JWCHSGD doses (high, medium, low). Viability and apoptosis were assessed via CCK-8 and flow cytometry. In vivo, 60 C57BL/6J mice were divided into six groups: control, model, carbamazepine, JWCHSGD, JWCHSGD + Sh Circ_Csnk1g3, and JWCHSGD + Sh NC. An epilepsy model was induced, and treatments were administered for two weeks. Outcomes included EEG, hippocampal histopathology, apoptosis (TUNEL), and mRNA/protein expression of key pathway markers. In HT22 cells, the model group showed reduced viability, increased apoptosis, and elevated mRNA/protein levels of Csnk1g3-85aa, RIP1, RIP3, MLKL, TNF-α, IL-6, and IL-1β (P < 0.05). JWCHSGD and carbamazepine increased viability and decreased apoptosis, reversing these molecular changes (P < 0.05). In mice, the model group had heightened epileptic discharges, neuronal damage, and apoptosis, along with increased expression of the same markers (P < 0.05). JWCHSGD and carbamazepine mitigated these effects (P < 0.05). JWCHSGD reduces epileptic events by regulating the circRNA-Csnk1g3/Csnk1g3-85aa/CK1γ3/TNF-α signaling pathway, impacting necroptosis and inflammation in hippocampal neurons and HT22 cells. |
| format | Article |
| id | doaj-art-85ec8806e35b42cb80be967b86966c92 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-85ec8806e35b42cb80be967b86966c922025-02-09T12:35:05ZengNature PortfolioScientific Reports2045-23222025-02-0115111910.1038/s41598-025-89275-8Mitigating effects of Jiawei Chaihu Shugan decoction on necroptosis and inflammation of hippocampal neurons in epileptic miceQin Wang0Baijun Qin1Han Yu2Jiawei Zeng3Jingjing Fan4Qiong Wu5Rong Zeng6Haichun Yu7Xian Zhang8Mingfen Li9Yanying Zhou10Limei Diao11The First Clinical School of Medicine, Guangxi University of Chinese MedicineDepartment of Gastroenterology, Chongqing City Hospital of Traditional Chinese MedicineHarbin Medical UniversityThe First Clinical School of Medicine, Guangxi University of Chinese MedicineThe First Clinical School of Medicine, Guangxi University of Chinese MedicineXinyang Central HospitalQinzhou Maternal and Child Health Hospital (Qinzhou Red Cross Hospital)Guangxi Technological College of Machinery and ElectricityGuangxi Zhuang Autonomous Region Brain HospitalDepartment of Neurology, The First Affiliated Hospital of Guangxi University of Chinese MedicineDepartment of Neurology, The First Affiliated Hospital of Guangxi University of Chinese MedicineThe First Clinical School of Medicine, Guangxi University of Chinese MedicineAbstract Jiawei Chaihu Shugan decoction (JWCHSGD) is a traditional Chinese medicine well-known for its beneficial effects in treating epilepsy (Xianzheng in ancient Chinese), but the molecular mechanism of its action remains unclear. To investigate the molecular mechanism of JWCHSGD’s prevention of epilepsy-mediated neuron from necroptosis and inflammation via the circRNA-Csnk1g3/Csnk1g3-85aa/ CK1γ3/TNF-α signal pathway. In vitro, murine neuronal HT22 cells were treated in six groups: control, model, carbamazepine, and three JWCHSGD doses (high, medium, low). Viability and apoptosis were assessed via CCK-8 and flow cytometry. In vivo, 60 C57BL/6J mice were divided into six groups: control, model, carbamazepine, JWCHSGD, JWCHSGD + Sh Circ_Csnk1g3, and JWCHSGD + Sh NC. An epilepsy model was induced, and treatments were administered for two weeks. Outcomes included EEG, hippocampal histopathology, apoptosis (TUNEL), and mRNA/protein expression of key pathway markers. In HT22 cells, the model group showed reduced viability, increased apoptosis, and elevated mRNA/protein levels of Csnk1g3-85aa, RIP1, RIP3, MLKL, TNF-α, IL-6, and IL-1β (P < 0.05). JWCHSGD and carbamazepine increased viability and decreased apoptosis, reversing these molecular changes (P < 0.05). In mice, the model group had heightened epileptic discharges, neuronal damage, and apoptosis, along with increased expression of the same markers (P < 0.05). JWCHSGD and carbamazepine mitigated these effects (P < 0.05). JWCHSGD reduces epileptic events by regulating the circRNA-Csnk1g3/Csnk1g3-85aa/CK1γ3/TNF-α signaling pathway, impacting necroptosis and inflammation in hippocampal neurons and HT22 cells.https://doi.org/10.1038/s41598-025-89275-8Jiawei Chaihu Shugan decoctionEpilepsyHippocampal neuronsNecroptosisInflammationSignaling pathway |
| spellingShingle | Qin Wang Baijun Qin Han Yu Jiawei Zeng Jingjing Fan Qiong Wu Rong Zeng Haichun Yu Xian Zhang Mingfen Li Yanying Zhou Limei Diao Mitigating effects of Jiawei Chaihu Shugan decoction on necroptosis and inflammation of hippocampal neurons in epileptic mice Scientific Reports Jiawei Chaihu Shugan decoction Epilepsy Hippocampal neurons Necroptosis Inflammation Signaling pathway |
| title | Mitigating effects of Jiawei Chaihu Shugan decoction on necroptosis and inflammation of hippocampal neurons in epileptic mice |
| title_full | Mitigating effects of Jiawei Chaihu Shugan decoction on necroptosis and inflammation of hippocampal neurons in epileptic mice |
| title_fullStr | Mitigating effects of Jiawei Chaihu Shugan decoction on necroptosis and inflammation of hippocampal neurons in epileptic mice |
| title_full_unstemmed | Mitigating effects of Jiawei Chaihu Shugan decoction on necroptosis and inflammation of hippocampal neurons in epileptic mice |
| title_short | Mitigating effects of Jiawei Chaihu Shugan decoction on necroptosis and inflammation of hippocampal neurons in epileptic mice |
| title_sort | mitigating effects of jiawei chaihu shugan decoction on necroptosis and inflammation of hippocampal neurons in epileptic mice |
| topic | Jiawei Chaihu Shugan decoction Epilepsy Hippocampal neurons Necroptosis Inflammation Signaling pathway |
| url | https://doi.org/10.1038/s41598-025-89275-8 |
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