Arisaema cum Bile Mitigate Febrile Seizure in Rats via Inhibition of Neuroinflammation, Regulation of FXR and GABA Signaling Pathway.

IF 4.2 2区医学 Q2 IMMUNOLOGY

Journal of Inflammation Research Pub Date : 2025-06-12 eCollection Date: 2025-01-01 DOI:10.2147/JIR.S508690

Xu Wu, Lian Zhong, Jing Wang, Qiao Zhang, Jing Sun, Changli Wang, Mengmeng Zhang, Chongbo Zhao

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引用次数: 0

Abstract

Background: Arisaema cum bile (known as DanNan Xing in Chinese, DNX) is a traditional herbal medicine commonly used to treat febrile seizure (FS), but the underlying mechanism remains unclear.

Objective: To evaluate the therapeutic effect of DNX on hot water bath-induced FS rat model and further explore the potential mechanism.

Methods: The chemical constituents of DNX were determined via liquid chromatography-mass spectrometry (LC-MS). FS rat model was established using a hot water bath (45 ± 2 °C), and DNX (2.8 and 0.7 g/kg, i.g) were administered for two weeks. Based on behavior test (duration and latency), pathological changes in the hippocampal tissue, and the levels of inflammatory cytokines the therapeutic effect of DNX for FS was evaluated. Subsequently, the network pharmacology, 16S rRNA and non-targeted metabolomics analysis were combined analysis to explore the potential signaling pathway. Furthermore, the signaling pathway was verified using the RT-qPCR and immunohistochemistry assay.

Results: The DNX treatment showed effective therapy on hot water bath induced FS, as indicated by a shortened seizure duration time, prolonged seizure latency, reduced hippocampal neuron damage and neuroinflammatory factor levels (TNF-α, IL-1β, IL-6, and HMGB1). Neurotransmitters (GABA, Glu) are also significantly regulated. Moreover, the relative abundance of Lactobacillus and Lachnospiraceae was notably increased (p < 0.01), while that of Tenericutes decreased, compared to gut microbiota of FS rat. A total of 20 fecal differential metabolites were regarded as the potential biomarkers including GABA, CDCA, and UDCA for anti-FS of DNX, and combined network pharmacy the metabolic pathways of primary bile acids (BAs) biosynthesis and alanine, aspartate and glutamate metabolism were involved.

Conclusion: DNX possesses a therapeutic effect on FS through inhibiting neuroinflammation and regulation of FXR and GABA signaling pathway.

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缬草胆汁通过抑制神经炎症、调节FXR和GABA信号通路减轻大鼠热性惊厥。

背景：胆南星是一种治疗发热性惊厥（FS）的传统中药，但其作用机制尚不清楚。目的：评价DNX对热水浴诱导的FS大鼠模型的治疗作用，并进一步探讨其作用机制。方法：采用液相色谱-质谱法（LC-MS）测定丹参的化学成分。采用热水浴法（45±2°C）建立FS大鼠模型，并给予DNX(2.8和0.7 g/kg, ig) 2周。通过行为学测试（持续时间和潜伏期）、海马组织病理变化和炎性细胞因子水平评价DNX治疗FS的效果。随后，结合网络药理学、16S rRNA和非靶向代谢组学分析，探索潜在的信号通路。此外，利用RT-qPCR和免疫组织化学分析验证了信号通路。结果：DNX治疗对热水浴诱导的FS有明显的治疗效果，表现为癫痫发作持续时间缩短，发作潜伏期延长，海马神经元损伤减少，神经炎症因子（TNF-α、IL-1β、IL-6、HMGB1）水平降低。神经递质（GABA, Glu）也受到显著调节。此外，与FS大鼠肠道菌群相比，乳杆菌科（Lactobacillus）和毛螺科（Lachnospiraceae）菌群的相对丰度显著增加（p < 0.01），而Tenericutes菌群的相对丰度则显著降低。将GABA、CDCA、UDCA等20种粪便差异代谢物作为DNX抗fs的潜在生物标志物，并结合网络药物研究了原胆汁酸（BAs）生物合成和丙氨酸、天冬氨酸、谷氨酸代谢的代谢途径。结论：DNX通过抑制神经炎症，调节FXR和GABA信号通路，对FS有治疗作用。

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

Journal of Inflammation Research Immunology and Microbiology-Immunology

CiteScore

6.10

自引率

2.20%

发文量

658

审稿时长

16 weeks

期刊介绍： An international, peer-reviewed, open access, online journal that welcomes laboratory and clinical findings on the molecular basis, cell biology and pharmacology of inflammation.