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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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-89275-8 |
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| Summary: | 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. |
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| ISSN: | 2045-2322 |