Exploring the therapeutic efficacy of Bai-Shao in mitigating comorbid epileptic seizures and cognitive impairment via inflammatory signaling pathways: insights from in silico and in vivo studies.

IF 2.9 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
3 Biotech Pub Date : 2025-06-01 Epub Date: 2025-05-15 DOI:10.1007/s13205-025-04316-3
Yanhong Yu, Hailing Lv, Xiaoyu Liu, Aiju Liu
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引用次数: 0

Abstract

Bai-Shao (BS) ingredients capable of crossing the blood-brain barrier (BBB) were identified and analyzed for their main gene targets. Genes associated with epileptic seizures (ES), cognitive impairment (CI), and inflammation were retrieved, with common targets between BS and these conditions determined via Venn analysis. Protein-protein interaction (PPI) analysis identified the top 10 key genes, whose correlations with apolipoprotein E (APOE) and methylenetetrahydrofolate reductase (MTHFR) were assessed. Functional pathways were explored using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), while molecular docking evaluated interactions between BS compounds and target proteins. Findings were validated in a pentylenetetrazol (PTZ)-induced mouse model. BS contains β-sitosterol and betulinic acid, both BBB-permeable, with 277 shared ES/CI-related targets identified. The top 10 genes correlated with APOE and MTHFR, and pathway analysis highlighted interleukin-17 (IL-17) and tumor necrosis factor (TNF) signaling, involving FOS proto-oncogene (FOS), jun proto-oncogene (JUN), caspase-3 (CASP3), phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and cyclooxygenase-2 (COX2). Behavioral tests, including the Open Field Test and Morris Water Maze, indicated cognitive and motor improvements in PTZ-treated mice. Molecular analysis revealed hippocampal regulation of key genes and altered TNF-alpha (TNFα), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) levels. In conclusion, BS demonstrates therapeutic potential for comorbid ES and CI by modulating inflammatory pathways and cell survival mechanisms, supporting its role in neurological research.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04316-3.

探索白芍通过炎症信号通路减轻癫痫共病发作和认知障碍的治疗效果:来自计算机和体内研究的见解。
对能穿越血脑屏障(BBB)的白芍(BS)成分进行了鉴定和主要基因靶点分析。检索了与癫痫发作(ES)、认知障碍(CI)和炎症相关的基因,并通过Venn分析确定了BS和这些疾病之间的共同目标。蛋白质-蛋白质相互作用(PPI)分析确定了前10个关键基因,并评估了它们与载脂蛋白E (APOE)和亚甲基四氢叶酸还原酶(MTHFR)的相关性。利用基因本体(GO)和京都基因与基因组百科全书(KEGG)探索功能途径,分子对接评估BS化合物与靶蛋白之间的相互作用。研究结果在戊四唑(PTZ)诱导的小鼠模型中得到了验证。BS含有β-谷甾醇和白桦树酸,两者都具有血脑屏障渗透性,并确定了277个共享ES/ ci相关靶点。与APOE和MTHFR相关的前10个基因,途径分析突出了白介素-17 (IL-17)和肿瘤坏死因子(TNF)信号,包括FOS原癌基因(FOS)、jun原癌基因(jun)、CASP3 -3、磷酸肌醇3激酶(PI3K)、蛋白激酶B (AKT)和环氧化酶-2 (COX2)。行为测试,包括开放场地测试和莫里斯水迷宫,表明ptz治疗小鼠的认知和运动改善。分子分析显示,海马调节了关键基因,改变了tnf - α (tnf - α)、白细胞介素-6 (IL-6)和白细胞介素-1β (IL-1β)水平。综上所述,BS通过调节炎症通路和细胞存活机制,显示出治疗ES和CI合并症的潜力,支持其在神经学研究中的作用。补充信息:在线版本包含补充资料,可在10.1007/s13205-025-04316-3获得。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
3 Biotech
3 Biotech Agricultural and Biological Sciences-Agricultural and Biological Sciences (miscellaneous)
CiteScore
6.00
自引率
0.00%
发文量
314
期刊介绍: 3 Biotech publishes the results of the latest research related to the study and application of biotechnology to: - Medicine and Biomedical Sciences - Agriculture - The Environment The focus on these three technology sectors recognizes that complete Biotechnology applications often require a combination of techniques. 3 Biotech not only presents the latest developments in biotechnology but also addresses the problems and benefits of integrating a variety of techniques for a particular application. 3 Biotech will appeal to scientists and engineers in both academia and industry focused on the safe and efficient application of Biotechnology to Medicine, Agriculture and the Environment.
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