天然熊胆粉通过调节 TGR5/AKT/NF-κB 信号通路抑制脂多糖处理的小鼠神经炎症。
Natural bear bile powder suppresses neuroinflammation in lipopolysaccharide-treated mice via regulating TGR5/AKT/NF-κB signaling pathway.
机构信息
Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, The State Administration of TCM (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
出版信息
J Ethnopharmacol. 2022 May 10;289:115063. doi: 10.1016/j.jep.2022.115063. Epub 2022 Feb 9.
ETHNOPHARMACOLOGICAL RELEVANCE
According to the Tang Dynasty classics Dietetic Material Medica and the Ming Dynasty classics Compendium of Materia Medica records, bear bile powder (BBP) has been used to treat a variety of diseases, such as febrile seizures, the pathogenesis of which is associated to neuroinflammation. However, the mechanism of BBP on alleviating neuroinflammation remains unclear.
AIMS OF THE STUDY
Microglia can be activated by peripheral lipopolysaccharide (LPS) and play an important role in the pathogenesis of neuroinflammation. The purpose of this study is to investigate the effects and mechanism of BBP in inhibiting LPS-induced microglia inflammation in vitro and in vivo.
MATERIALS AND METHODS
The anti-microglia inflammatory effects and mechanism of BBP were assessed in LPS-treated BV2 microglial cells and in LPS-treated mice. The mRNA expression levels of the inflammatory factor and the protein expressions of cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), takeda G-protein coupled receptor 5 (TGR5), nuclear factor-κB (NF-κB), inhibitor of NF-κB (IκBɑ), protein kinase B (AKT) in BV2 cells, mouse hippocampus and cortex were detected. The NF-κB transcription activity and NF-κB nuclear translocation were observed.
RESULTS
Our findings showed that BBP reduces branched process retraction and NO in LPS-treated BV2 cells, inhibits the protein expression of ionized calcium binding adaptor molecule 1 in the hippocampus of LPS-treated mice. Moreover, we observed that BBP decreases tumor necrosis factor α, interleukin (IL)-6 and IL-1β mRNA levels, deceases iNOS and COX-2 protein levels, increases TGR5 protein levels, suppresses the phosphorylation of AKT, NF-κB and IκBɑ protein in microglia both in vitro and in vivo. Further, we found that triamterene, the inhibitor of TGR5, abolishes the effects of BBP in LPS- treated BV2 cells.
CONCLUSION
BBP inhibits LPS-induced microglia activation, and the mechanism of its action is partly through TGR5/AKT/NF-κB signaling pathway.
民族药理学相关性
根据唐代本草学著作《食疗本草》和明代本草学著作《本草纲目》的记载，熊胆粉（BBP）已被用于治疗多种疾病，如热性惊厥，其发病机制与神经炎症有关。然而，BBP 缓解神经炎症的机制尚不清楚。
研究目的
小胶质细胞可被外周脂多糖（LPS）激活，并在神经炎症发病机制中发挥重要作用。本研究旨在探讨 BBP 抑制 LPS 诱导的体外和体内小胶质细胞炎症的作用及其机制。
材料和方法
在 LPS 处理的 BV2 小胶质细胞和 LPS 处理的小鼠中评估 BBP 的抗小胶质细胞炎症作用和机制。检测 LPS 处理的 BV2 细胞中炎症因子的 mRNA 表达水平以及环氧化酶-2（COX2）、诱导型一氧化氮合酶（iNOS）、武田 G 蛋白偶联受体 5（TGR5）、核因子-κB（NF-κB）、NF-κB 抑制剂（IκBα）、蛋白激酶 B（AKT）的蛋白表达。观察 NF-κB 转录活性和 NF-κB 核转位。
结果
我们的研究结果表明，BBP 可减少 LPS 处理的 BV2 细胞中分支过程回缩和 NO，抑制 LPS 处理的小鼠海马 CA1 区离子钙结合接头分子 1 的蛋白表达。此外，我们观察到 BBP 降低肿瘤坏死因子-α、白细胞介素（IL）-6 和 IL-1β 的 mRNA 水平，降低 iNOS 和 COX-2 蛋白水平，增加 TGR5 蛋白水平，抑制 AKT、NF-κB 和 IκBα蛋白在体外和体内的磷酸化。此外，我们发现三氨喋呤，TGR5 的抑制剂，可消除 BBP 在 LPS 处理的 BV2 细胞中的作用。
结论
BBP 抑制 LPS 诱导的小胶质细胞激活，其作用机制部分通过 TGR5/AKT/NF-κB 信号通路。
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