Anti-convulsant effects of cultures bear bile powder in febrile seizure via regulation of neurotransmission and inhibition of neuroinflammation.,Journal of Ethnopharmacology

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Anti-convulsant effects of cultures bear bile powder in febrile seizure via regulation of neurotransmission and inhibition of neuroinflammation.
Journal of Ethnopharmacology ( IF 4.8 ) Pub Date : 2020-05-30 , DOI: 10.1016/j.jep.2020.112998
Xiaoshu Sun ₁ , Haoyu Xue ₁ , Bin Zan ₁ , Yining Zhao ₁ , Yuanyuan Li ₁ , Tianming Wang ₁ , Jiasheng Wu ₁ , Shaoyong Liu ₂ , Zhengtao Wang ₃ , Rong Shi ₁ , Li Yang ₄ , Yueming Ma ₅

Affiliation

Ethnopharmacological relevance

Natural bear bile powder (NBBP) has been used to treat seizures for thousands of years, but its application is greatly restricted due to ethical reasons. Cultured bear bile powder (CBBP), which is produced by biotransformation, may be an appropriate substitute for NBBP. However, the anti-convulsant effects of CBBP and its mechanisms remain unclear.

Aim of the study

This study aimed to investigate the anti-convulsant effects and possible mechanisms of CBBP in a febrile seizure (FS) rat model.

Materials and methods

FS was induced by placing the rats in a warm water bath (45.5 °C). The incidence rate and latency of FS, and hematoxylin-eosin staining (HE) were conducted for neurological damage. The levels of 4 bile acids and 8 main neurotransmitters in vivo were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The expression of bile acid related transports, neurotransmitter receptors, inflammatory factors, neurotrophic factors and glial fibrillary acidic protein (GFAP) in hippocampal tissues were detected by real-time PCR, western blotting, and immunohistochemistry.

Results

Pre-treatments with CBBP and similarly, NBBP, significantly reduced the incidence rate and prolonged the latency of FS. Additionally, CBBP alleviated the histological injury induced by FS in the rat hippocampus tissue. LC-MS/MS analyses revealed that CBBP markedly increased the levels of tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), ursodeoxycholic acid (UDCA), and chenodeoxycholic acid (CDCA) in FS rats. Furthermore, the content of gamma-aminobutyric acid (GABA) was up-regulated in rats pre-treated with CBBP whereas GFAP was down-regulated. CBBP also significantly suppressed the expression of interleukin -1β (IL-1β), tumor necrosis factor α (TNF-α), nuclear factor kappa B (NF-κB), and brain-derived neurotrophic factor (BDNF) and its TrkB receptors, and improved the expression of GABA type A receptors (GABA_AR) and farnesoid X receptors (FXR).

Conclusions

The present study demonstrated that CBBP had anti-convulsant effects in a FS rat model. CBBP may protect rats against FS, probably by up-regulating FXR, which was activated by increasing brain bile acids, up-regulating GABAergic transmission by inhibiting BDNF-TrkB signaling, and suppressing neuroinflammation by inhibiting the NF-κB pathway.

中文翻译：

培养物的抗惊厥作用通过调节神经传递和抑制神经发炎，在高热惊厥中具有胆汁粉末。

民族药理学意义

天然熊胆粉（NBBP）已用于治疗癫痫发作数千年，但由于伦理原因，其应用受到了极大限制。通过生物转化生产的培养的熊胆粉（CBBP）可能是NBBP的合适替代品。但是，CBBP的抗惊厥作用及其机制尚不清楚。

研究目的

这项研究旨在调查高热惊厥（FS）大鼠模型中CBBP的抗惊厥作用和可能的机制。

材料和方法

通过将大鼠置于温水浴（45.5°C）中诱导FS。进行FS的发生率和潜伏期以及苏木精-伊红染色（HE）进行神经系统损害。通过液相色谱-串联质谱法（LC-MS / MS）测量体内4种胆汁酸和8种主要神经递质的水平。实时荧光定量PCR，免疫印迹和免疫组化检测海马组织中胆汁酸相关转运，神经递质受体，炎症因子，神经营养因子和神经胶质原纤维酸性蛋白（GFAP）的表达。

结果

用CBBP和类似的NBBP进行预处理可显着降低FS的发生率并延长FS的潜伏期。另外，CBBP减轻了FS在大鼠海马组织中诱导的组织学损伤。LC-MS / MS分析显示，CBBP在FS大鼠中显着增加了牛磺去氧胆酸（TUDCA），牛磺去氧胆酸（TCDCA），熊去氧胆酸（UDCA）和鹅去氧胆酸（CDCA）的水平。此外，用CBBP预处理的大鼠中的γ-氨基丁酸（GABA）含量上调，而GFAP则下调。CBBP还显着抑制白介素-1β（IL-1β），肿瘤坏死因子α（TNF-α），核因子κB（NF-κB）和脑源性神经营养因子（BDNF）及其TrkB受体的表达，并改善了GABA A型受体（GABA_A R）和法尼醇X受体（FXR）。