Activity-based chemical proteomics reveals caffeic acid ameliorates pentylenetetrazol-induced seizures by covalently targeting aconitate decarboxylase 1
Abstract Background Epilepsy is a neurological disorder characterized by recurrent seizures, tightly associated with neuroinflammation. Activation of inflammatory cells and molecules in damaged nervous tissues plays a pivotal role in epilepsy. Caffeic acid, one of the most abundant polyphenols in co...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-02-01
|
| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-024-01739-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823861770894180352 |
|---|---|
| author | Guanjun Li Ling Huang Di Gu Peili Wang Letai Yi Wenhua Kuang Ying Zhang Junzhe Zhang Dandan Liu Qiaoli Shi Huan Tang Jichao Sun Guohua Zeng Xin Peng Jigang Wang |
| author_facet | Guanjun Li Ling Huang Di Gu Peili Wang Letai Yi Wenhua Kuang Ying Zhang Junzhe Zhang Dandan Liu Qiaoli Shi Huan Tang Jichao Sun Guohua Zeng Xin Peng Jigang Wang |
| author_sort | Guanjun Li |
| collection | DOAJ |
| description | Abstract Background Epilepsy is a neurological disorder characterized by recurrent seizures, tightly associated with neuroinflammation. Activation of inflammatory cells and molecules in damaged nervous tissues plays a pivotal role in epilepsy. Caffeic acid, one of the most abundant polyphenols in coffee, has shown potent protective effects as a phytomedicine in various neurological disorders. However, the direct protein targets and exact molecular mechanisms of caffeic acid in epilepsy, remain largely elusive. Purpose This study aimed to explore the protective effects of caffeic acid in epilepsy and elucidate its underlying mechanism. Methods In this study, we established pentylenetetrazol-induced acute and kindling models of seizures. Additionally, a BV2 microglial cellular inflammation model was established by lipopolysaccharide stimulation. The potential direct protein targets of caffeic acid in BV2 cells were analyzed using an activity-based protein profiling (ABPP) with a caffeic acid probe. Various methods such as pull-down assay, immunofluorescence and cellular heat transfer assays were used for experimental validation. The anti-inflammatory effects of caffeic acid in LPS-activated BV2 cells was proved by knocking down the target protein. Results Here, we found that caffeic acid exhibits antiepileptic effects in pentylenetetrazol-induced epilepsy mice and exerts anti-neuroinflammation effect in vivo and in vitro. Besides, we discovered that caffeic acid directly binds to aconitate decarboxylase 1 and influenced its enzymatic activity. Moreover, we indicated that caffeic acid exhibits anti-neuroinflammation effect through aconitate decarboxylase 1 mediated PERK-NF-κB pathway in vitro. Conclusion In summary, this study elucidates, for the first time, the potential antiepileptic targets and mechanism of action of caffeic acid using the ABPP strategy. Our study provides evidence supporting the utilization of caffeic acid as a promising therapeutic agent for treating epilepsy and neuroinflammation-related disorders. |
| format | Article |
| id | doaj-art-f2ed026be5a1421da9e04fdfc898b4fd |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-f2ed026be5a1421da9e04fdfc898b4fd2025-02-09T12:47:24ZengBMCCell Communication and Signaling1478-811X2025-02-0123111510.1186/s12964-024-01739-yActivity-based chemical proteomics reveals caffeic acid ameliorates pentylenetetrazol-induced seizures by covalently targeting aconitate decarboxylase 1Guanjun Li0Ling Huang1Di Gu2Peili Wang3Letai Yi4Wenhua Kuang5Ying Zhang6Junzhe Zhang7Dandan Liu8Qiaoli Shi9Huan Tang10Jichao Sun11Guohua Zeng12Xin Peng13Jigang Wang14Department of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)Department of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical UniversityXiyuan Hospital, National Clinical Research Center for Chinese Medicine Cardiology, Academy of Chinese Medical SciencesInner Mongolia Medical UniversityDepartment of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical SciencesState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical SciencesState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical SciencesState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical SciencesState Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical SciencesDepartment of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical UniversityNingbo Municipal Hospital of TCM, Affiliated Hospital of Zhejiang Chinese Medical UniversityDepartment of Urology, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)Abstract Background Epilepsy is a neurological disorder characterized by recurrent seizures, tightly associated with neuroinflammation. Activation of inflammatory cells and molecules in damaged nervous tissues plays a pivotal role in epilepsy. Caffeic acid, one of the most abundant polyphenols in coffee, has shown potent protective effects as a phytomedicine in various neurological disorders. However, the direct protein targets and exact molecular mechanisms of caffeic acid in epilepsy, remain largely elusive. Purpose This study aimed to explore the protective effects of caffeic acid in epilepsy and elucidate its underlying mechanism. Methods In this study, we established pentylenetetrazol-induced acute and kindling models of seizures. Additionally, a BV2 microglial cellular inflammation model was established by lipopolysaccharide stimulation. The potential direct protein targets of caffeic acid in BV2 cells were analyzed using an activity-based protein profiling (ABPP) with a caffeic acid probe. Various methods such as pull-down assay, immunofluorescence and cellular heat transfer assays were used for experimental validation. The anti-inflammatory effects of caffeic acid in LPS-activated BV2 cells was proved by knocking down the target protein. Results Here, we found that caffeic acid exhibits antiepileptic effects in pentylenetetrazol-induced epilepsy mice and exerts anti-neuroinflammation effect in vivo and in vitro. Besides, we discovered that caffeic acid directly binds to aconitate decarboxylase 1 and influenced its enzymatic activity. Moreover, we indicated that caffeic acid exhibits anti-neuroinflammation effect through aconitate decarboxylase 1 mediated PERK-NF-κB pathway in vitro. Conclusion In summary, this study elucidates, for the first time, the potential antiepileptic targets and mechanism of action of caffeic acid using the ABPP strategy. Our study provides evidence supporting the utilization of caffeic acid as a promising therapeutic agent for treating epilepsy and neuroinflammation-related disorders.https://doi.org/10.1186/s12964-024-01739-yPhytomedicineNatural products and herbsNetwork pharmacologyActivity-based chemical proteomic |
| spellingShingle | Guanjun Li Ling Huang Di Gu Peili Wang Letai Yi Wenhua Kuang Ying Zhang Junzhe Zhang Dandan Liu Qiaoli Shi Huan Tang Jichao Sun Guohua Zeng Xin Peng Jigang Wang Activity-based chemical proteomics reveals caffeic acid ameliorates pentylenetetrazol-induced seizures by covalently targeting aconitate decarboxylase 1 Cell Communication and Signaling Phytomedicine Natural products and herbs Network pharmacology Activity-based chemical proteomic |
| title | Activity-based chemical proteomics reveals caffeic acid ameliorates pentylenetetrazol-induced seizures by covalently targeting aconitate decarboxylase 1 |
| title_full | Activity-based chemical proteomics reveals caffeic acid ameliorates pentylenetetrazol-induced seizures by covalently targeting aconitate decarboxylase 1 |
| title_fullStr | Activity-based chemical proteomics reveals caffeic acid ameliorates pentylenetetrazol-induced seizures by covalently targeting aconitate decarboxylase 1 |
| title_full_unstemmed | Activity-based chemical proteomics reveals caffeic acid ameliorates pentylenetetrazol-induced seizures by covalently targeting aconitate decarboxylase 1 |
| title_short | Activity-based chemical proteomics reveals caffeic acid ameliorates pentylenetetrazol-induced seizures by covalently targeting aconitate decarboxylase 1 |
| title_sort | activity based chemical proteomics reveals caffeic acid ameliorates pentylenetetrazol induced seizures by covalently targeting aconitate decarboxylase 1 |
| topic | Phytomedicine Natural products and herbs Network pharmacology Activity-based chemical proteomic |
| url | https://doi.org/10.1186/s12964-024-01739-y |
| work_keys_str_mv | AT guanjunli activitybasedchemicalproteomicsrevealscaffeicacidamelioratespentylenetetrazolinducedseizuresbycovalentlytargetingaconitatedecarboxylase1 AT linghuang activitybasedchemicalproteomicsrevealscaffeicacidamelioratespentylenetetrazolinducedseizuresbycovalentlytargetingaconitatedecarboxylase1 AT digu activitybasedchemicalproteomicsrevealscaffeicacidamelioratespentylenetetrazolinducedseizuresbycovalentlytargetingaconitatedecarboxylase1 AT peiliwang activitybasedchemicalproteomicsrevealscaffeicacidamelioratespentylenetetrazolinducedseizuresbycovalentlytargetingaconitatedecarboxylase1 AT letaiyi activitybasedchemicalproteomicsrevealscaffeicacidamelioratespentylenetetrazolinducedseizuresbycovalentlytargetingaconitatedecarboxylase1 AT wenhuakuang activitybasedchemicalproteomicsrevealscaffeicacidamelioratespentylenetetrazolinducedseizuresbycovalentlytargetingaconitatedecarboxylase1 AT yingzhang activitybasedchemicalproteomicsrevealscaffeicacidamelioratespentylenetetrazolinducedseizuresbycovalentlytargetingaconitatedecarboxylase1 AT junzhezhang activitybasedchemicalproteomicsrevealscaffeicacidamelioratespentylenetetrazolinducedseizuresbycovalentlytargetingaconitatedecarboxylase1 AT dandanliu activitybasedchemicalproteomicsrevealscaffeicacidamelioratespentylenetetrazolinducedseizuresbycovalentlytargetingaconitatedecarboxylase1 AT qiaolishi activitybasedchemicalproteomicsrevealscaffeicacidamelioratespentylenetetrazolinducedseizuresbycovalentlytargetingaconitatedecarboxylase1 AT huantang activitybasedchemicalproteomicsrevealscaffeicacidamelioratespentylenetetrazolinducedseizuresbycovalentlytargetingaconitatedecarboxylase1 AT jichaosun activitybasedchemicalproteomicsrevealscaffeicacidamelioratespentylenetetrazolinducedseizuresbycovalentlytargetingaconitatedecarboxylase1 AT guohuazeng activitybasedchemicalproteomicsrevealscaffeicacidamelioratespentylenetetrazolinducedseizuresbycovalentlytargetingaconitatedecarboxylase1 AT xinpeng activitybasedchemicalproteomicsrevealscaffeicacidamelioratespentylenetetrazolinducedseizuresbycovalentlytargetingaconitatedecarboxylase1 AT jigangwang activitybasedchemicalproteomicsrevealscaffeicacidamelioratespentylenetetrazolinducedseizuresbycovalentlytargetingaconitatedecarboxylase1 |