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急性卡瓦胡椒醇治疗可减轻创伤性脑损伤的神经炎症和功能缺陷。

Acute Kahweol Treatment Attenuates Traumatic Brain Injury Neuroinflammation and Functional Deficits.

机构信息

Department of Neurosurgery, Cheng Hsin General Hospital, Taipei 11220, Taiwan.

Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.

出版信息

Nutrients. 2019 Sep 27;11(10):2301. doi: 10.3390/nu11102301.

DOI:10.3390/nu11102301
PMID:31569604
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6835740/
Abstract

Traumatic brain injury (TBI) affects millions worldwide with devastating long-term effects on health and cognition. Emerging data suggest that targeting the immune response may offer promising strategies to alleviate TBI outcomes; kahweol, an anti-inflammatory diterpene that remains in unfiltered coffee, has been shown to be beneficial in neuronal recovery. Here, we examined whether kahweol could alleviate brain trauma-induced injury in a mouse model of TBI and its underlying mechanisms. TBI was induced by controlled cortical impact (CCI) and various doses of kahweol were intraperitoneally administered following injury. Contusion volume, brain edema, neurobehavioral deficits, and protein expression and activity were evaluated in both short-term and long-term recovery. We found that kahweol treatments significantly reduced secondary brain injury and improved neurobehavioral outcomes in TBI mice. These changes were accompanied by the attenuation of proinflammatory cytokine secretion, decreased microglia/macrophage activation, and reduction of neutrophil and leukocyte infiltration. In addition, continuous kahweol treatment further improved short-term TBI outcomes compared to single-dosage. Collectively, our data showed that kahweol protects against TBI by reducing immune responses and may serve as a potential therapeutic intervention for TBI patients.

摘要

创伤性脑损伤(TBI)影响着全球数百万人,对健康和认知造成了毁灭性的长期影响。新出现的数据表明,靶向免疫反应可能提供缓解 TBI 结果的有希望的策略;存在于未经过滤咖啡中的抗炎二萜咖啡醇已被证明有益于神经元恢复。在这里,我们研究了 kahweol 是否可以减轻 TBI 小鼠模型中的脑创伤诱导损伤及其潜在机制。通过皮质控制冲击(CCI)诱导 TBI,并在损伤后通过腹膜内给予各种剂量的 kahweol。在短期和长期恢复中评估挫伤体积、脑水肿、神经行为缺陷以及蛋白质表达和活性。我们发现 kahweol 治疗可显著减轻 TBI 小鼠的继发性脑损伤并改善神经行为结果。这些变化伴随着促炎细胞因子分泌的减少、小胶质细胞/巨噬细胞激活的减少以及中性粒细胞和白细胞浸润的减少。此外,与单次剂量相比,连续 kahweol 治疗进一步改善了短期 TBI 结果。总的来说,我们的数据表明 kahweol 通过减少免疫反应来保护 TBI,并且可能成为 TBI 患者的潜在治疗干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47e9/6835740/2d6a6095e239/nutrients-11-02301-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47e9/6835740/53ddeaadf3ac/nutrients-11-02301-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47e9/6835740/4431f8731afa/nutrients-11-02301-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47e9/6835740/543cd00a23dd/nutrients-11-02301-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47e9/6835740/8c8ad897fcfd/nutrients-11-02301-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47e9/6835740/2d6a6095e239/nutrients-11-02301-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47e9/6835740/53ddeaadf3ac/nutrients-11-02301-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47e9/6835740/4431f8731afa/nutrients-11-02301-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47e9/6835740/543cd00a23dd/nutrients-11-02301-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47e9/6835740/8c8ad897fcfd/nutrients-11-02301-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47e9/6835740/2d6a6095e239/nutrients-11-02301-g005.jpg

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The effects of kahweol, a diterpene present in coffee, on the mitochondria of the human neuroblastoma SH-SY5Y cells exposed to hydrogen peroxide.咖啡中二萜类化合物卡瓦胡椒醇对过氧化氢处理的人神经母细胞瘤 SH-SY5Y 细胞线粒体的影响。
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Coffee diterpenes kahweol acetate and cafestol synergistically inhibit the proliferation and migration of prostate cancer cells.咖啡二萜醇咖啡酸酯和咖啡醇协同抑制前列腺癌细胞的增殖和迁移。
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Kahweol inhibits proliferation and induces apoptosis by suppressing fatty acid synthase in HER2-overexpressing cancer cells.卡瓦醇通过抑制脂肪酸合酶抑制 HER2 过表达癌细胞的增殖并诱导其凋亡。
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Kahweol Ameliorates the Liver Inflammation through the Inhibition of NF-κB and STAT3 Activation in Primary Kupffer Cells and Primary Hepatocytes.卡瓦醇通过抑制原代枯否细胞和原代肝细胞中的 NF-κB 和 STAT3 活化来减轻肝脏炎症。
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