- 中国精品科技期刊
- 中国高校百佳科技期刊
- 中国中文核心期刊
- 中国科学引文数据库核心期刊
| Citation: |
LI Juanjuan, HUANG Yue, WANG Yahe, et al. Antiepileptic and neuroprotective mechanism of ursolic acid based on full-length transcriptome analysis[J]. J China Pharm Univ, 2024, 55(4): 512 − 521. DOI: 10.11665/j.issn.1000-5048.2023111303
|
This study explores the potential antiepileptic mechanism of ursolic acid (UA) and its improvement of GABAergic interneuron damage induced by epilepsy based on transcriptome analysis. Hippocampal tissues from rats in the control group (NC group), epilepsy group (SE group), and epilepsy UA treatment group (UA group) were subjected to full-length transcriptome sequencing. The obtained sequencing data were analyzed, using gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) to perform the analysis of differential genes (DEGs). The expression levels of key differential genes were verified using RT-qPCR in hippocampal tissue. Finally, an epilepsy in vitro model was constructed on primary neurons, RT-qPCR was used to verify the expression levels of key differential genes, and the expression level of GABAA receptor γ2 subunit (GABRG2) on neurons was further examined using immunofluorescence and Western blot. The heatmap of pairwise sample expression correlation and the clustering analysis of differentially expressed genes showed that the SE group was farthest from the NC group, and that after UA treatment, the overall trend shifted towards the normal group. Compared with the SE group, a total of 220 differential genes were screened in the UA group, including 143 upregulated genes and 77 downregulated genes. GO enrichment analysis showed that it involved three processes in the primary classification: biological processes, cellular components, and molecular functions. KEGG pathway enrichment analysis showed that DEGs were involved in 36 biological pathways, including cAMP signaling pathway and calcium signaling pathway. PPI analysis showed that DEGs were closely related to GABA and inflammation. RT-qPCR results showed that UA treatment increased the expression levels of GABA receptor-related gene (Gng4), GABA synthesis-related gene (Camk2a,Vgf, and Npy) and inflammation-related gene (Timp1 and Spp1) in hippocampal tissue, and decreased the expression levels of GABA synthesis-related gene (Nptx2) and cAMP-related pathway gene (Gnas). It further confirmed that UA treatment increased the expression levels of Gng4 and Camk2a on neurons and decreased the expression level of Gnas. Immunofluorescence and Western blot results showed that, compared with the SE group, the expression level of GABRG2 on primary neurons increased after UA treatment. This study enriched the transcriptome data of UA's antiepileptic effect and laid a theoretical foundation for further research on UA's antiepileptic and neuroprotective effects.
| [1] |
Kanner AM, Bicchi MM. Antiseizure medications for adults with epilepsy: a review[J]. JAMA, 2022, 327(13): 1269-1281. doi: 10.1001/jama.2022.3880
|
| [2] |
Lin YC, Hu SM, Hao XY, et al. Epilepsy centers in China: current status and ways forward[J]. Epilepsia, 2021, 62(11): 2640-2650. doi: 10.1111/epi.17058
|
| [3] |
Singh A, Trevick S. The epidemiology of global epilepsy[J]. Neurol Clin, 2016, 34(4): 837-847. doi: 10.1016/j.ncl.2016.06.015
|
| [4] |
Ding D, Zhou D, Sander JW, et al. Epilepsy in China: major progress in the past two decades[J]. Lancet Neurol, 2021, 20(4): 316-326. doi: 10.1016/S1474-4422(21)00023-5
|
| [5] |
Treiman DM. GABAergic mechanisms in epilepsy[J]. Epilepsia, 2001, 42(Suppl 3): 8-12.
|
| [6] |
Shetty AK, Upadhya D. GABA-ergic cell therapy for epilepsy: advances, limitations and challenges[J]. Neurosci Biobehav Rev, 2016, 62: 35-47. doi: 10.1016/j.neubiorev.2015.12.014
|
| [7] |
Sills GJ, Rogawski MA. Mechanisms of action of currently used antiseizure drugs[J]. Neuropharmacology, 2020, 168: 107966. doi: 10.1016/j.neuropharm.2020.107966
|
| [8] |
Mirza FJ, Zahid S. Ursolic acid and rosmarinic acid ameliorate alterations in hippocampal neurogenesis and social memory induced by amyloid beta in mouse model of Alzheimer’s disease[J]. Front Pharmacol, 2022, 13: 1058358. doi: 10.3389/fphar.2022.1058358
|
| [9] |
Bang Y, Kwon Y, Kim M, et al. Ursolic acid enhances autophagic clearance and ameliorates motor and non-motor symptoms in Parkinson’s disease mice model[J]. Acta Pharmacol Sin, 2023, 44(4): 752-765. doi: 10.1038/s41401-022-00988-2
|
| [10] |
Liu KM, Huang Y, Wan PP, et al. Ursolic acid protects neurons in temporal lobe epilepsy and cognitive impairment by repressing inflammation and oxidation[J]. Front Pharmacol, 2022, 13: 877898. doi: 10.3389/fphar.2022.877898
|
| [11] |
Lin AL, Guo Y, Zhang H, et al. GSDMD knockdown exacerbates hippocampal damage and seizure susceptibility by crosstalk between pyroptosis and apoptosis in kainic acid-induced temporal lobe epilepsy[J]. Biochim Biophys Acta Mol Basis Dis, 2023, 1869(5): 166687. doi: 10.1016/j.bbadis.2023.166687
|
| [12] |
Zeng XC, Hu K, Chen LL, et al. The effects of ginsenoside compound K against epilepsy by enhancing the γ-aminobutyric acid signaling pathway[J]. Front Pharmacol, 2018, 9: 1020. doi: 10.3389/fphar.2018.01020
|
| [13] |
Zheng J, Yin F, Jin GQ, et al. In vitro neuroprotection of rat hippocampal neurons by manninotriose and astragaloside IV against corticosterone-induced toxicity[J]. Molecules, 2018, 23 (12): 3339.
|
| [14] |
Hu H, Miao YR, Jia LH, et al. AnimalTFDB 3.0: a comprehensive resource for annotation and prediction of animal transcription factors[J]. Nucleic Acids Res, 2019, 47(D1): D33-D38. doi: 10.1093/nar/gky822
|
| [15] |
Hernandez CC, Shen YW, Hu NN, et al. GABRG2 variants associated with febrile seizures[J]. Biomolecules, 2023, 13 (3): 414.
|
| [16] |
Li XX, Guo SN, Xu SY, et al. Neocortex- and hippocampus-specific deletion of Gabrg2 causes temperature-dependent seizures in mice[J]. Cell Death Dis, 2021, 12(6): 553. doi: 10.1038/s41419-021-03846-x
|
| [17] |
Kelly MP, Stein JM, Vecsey CG, et al. Developmental etiology for neuroanatomical and cognitive deficits in mice overexpressing Galphas, a G-protein subunit genetically linked to schizophrenia[J]. Mol Psychiatry, 2009, 14(4): 398-415,347. doi: 10.1038/mp.2008.124
|
| [18] |
Favuzzi E, Huang SH, Saldi GA, et al. GABA-receptive microglia selectively sculpt developing inhibitory circuits[J]. Cell, 2021, 184(22): 5686. doi: 10.1016/j.cell.2021.10.009
|
| [19] |
Pelkey KA, Barksdale E, Craig MT, et al. Pentraxins coordinate excitatory synapse maturation and circuit integration of parvalbumin interneurons[J]. Neuron, 2015, 85(6): 1257-1272. doi: 10.1016/j.neuron.2015.02.020
|
| [20] |
Lisman J, Schulman H, Cline H. The molecular basis of CaMKII function in synaptic and behavioural memory[J]. Nat Rev Neurosci, 2002, 3(3): 175-190. doi: 10.1038/nrn753
|
| [21] |
Cattaneo S, Verlengia G, Marino P, et al. NPY and gene therapy for epilepsy: how, when, and Y[J]. Front Mol Neurosci, 2021, 13 : 608001.
|
| [22] |
Segura MF, Sole C, Pascual M, et al. The long form of Fas apoptotic inhibitory molecule is expressed specifically in neurons and protects them against death receptor-triggered apoptosis[J]. J Neurosci, 2007, 27(42): 11228-11241. doi: 10.1523/JNEUROSCI.3462-07.2007
|
| [1] | ZHOU Ying, ZHAO Xun, HU Nan, WANG Baocheng, YUAN Yaozuo. A method for rapid analysis of polysorbate 80 components[J]. Journal of China Pharmaceutical University, 2022, 53(2): 192-199. DOI: 10.11665/j.issn.1000-5048.20220209 |
| [2] | ZHOU Min, GAO Huixin, FENG Yi, ZENG Zhaoqing, TIAN Hui. Analysis on genetic diversity of Hedyotis diffusa Willd.by inter simple sequence repeat(ISSR)[J]. Journal of China Pharmaceutical University, 2019, 50(2): 200-205. DOI: 10.11665/j.issn.1000-5048.20190211 |
| [3] | ZOU Fuxian, XU Wen, HUANG Zehao, ZHANG Xun, CHEN Shuyun, LIN Yu, XU Wei. Analysis of transcriptome sequencing and related genes of flavonoid biosynthesis from Anoectochilus roxburghii[J]. Journal of China Pharmaceutical University, 2019, 50(1): 66-74. DOI: 10.11665/j.issn.1000-5048.20190109 |
| [4] | YAO Jian, SHAO Lei, CHEN Daijie, ZHANG Yubin. Transcriptomic analysis of a spiramycin I-resistant Staphylococcus aureus mutant[J]. Journal of China Pharmaceutical University, 2017, 48(6): 738-744. DOI: 10.11665/j.issn.1000-5048.20170617 |
| [5] | HU Jing, FAN Hua, YIN Jian. Effects of N-acyl glucosamines on GABA uptake activity of GABA transporter 1[J]. Journal of China Pharmaceutical University, 2016, 47(2): 228-234. DOI: 10.11665/j.issn.1000-5048.20160217 |
| [6] | DI Bin, SU Mengxiang. Analysis methods and strategies in drug research[J]. Journal of China Pharmaceutical University, 2013, 44(1): 20-27. DOI: 10.11665/j.issn.1000-5048.20130103 |
| [7] | HPLC Analysis of Metoprolol and Its Metabolites in the Perfusates[J]. Journal of China Pharmaceutical University, 1997, (6): 31-35. |
| [8] | NMR Analysis of Bromocriptine Mesilate Tenoxicam[J]. Journal of China Pharmaceutical University, 1997, (5): 33-35. |
| [10] | ANALYSIS OF TWENTY EIGHT ELEMENTS IN CHINESE DRUG MAIDONG[J]. Journal of China Pharmaceutical University, 1986, (4): 286-288. |
Supported by: Beijing Renhe Information Technology Co., Ltd. 
Total visits：297540
DownLoad: