浆果籽油通过诱导 HO-1 和抑制 BV-2 小胶质细胞中的 NF-κB 机制来预防 TNF-α 刺激的神经炎症。
var. Berry Seed Protects against TNF-α-Stimulated Neuroinflammation by Inducing HO-1 and Suppressing NF-κB Mechanism in BV-2 Microglial Cells.
机构信息
Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
出版信息
Molecules. 2023 Mar 29;28(7):3057. doi: 10.3390/molecules28073057.
Sustained inflammatory responses have been implicated in various neurodegenerative diseases (NDDs). var. (CN), an indigenous berry, has been reported to exhibit several health-beneficial properties. However, investigation of CN seeds is still limited. The objective of this study was to evaluate the protective effects of ethanolic seed extract (CNSE) and mechanisms in BV-2 mouse microglial cells using an inflammatory stimulus, TNF-α. Using LC-MS, ferulic acid, aurentiacin, brassitin, ellagic acid, and alpinetin were found in CNSE. Firstly, we examined molecular docking to elucidate its bioactive components on inflammation-related mechanisms. The results revealed that alpinetin, aurentiacin, and ellagic acid inhibited the NF-κB activation and iNOS function, while alpinetin and aurentiacin only suppressed the COX-2 function. Our cell-based investigation exhibited that cells pretreated with CNSE (5, 10, and 25 μg/mL) reduced the number of spindle cells, which was highly observed in TNF-α treatment (10 ng/mL). CNSE also obstructed TNF-α, IL-1β, and IL-6 mRNA levels and repressed the TNF-α and IL-6 releases in a culture medium of BV-2 cells. Remarkably, CNSE decreased the phosphorylated forms of ERK, p38MAPK, p65, and IκB-α related to the inhibition of NF-κB binding activity. CNSE obviously induced HO-1 protein expression. Our findings suggest that CNSE offers good potential for preventing inflammatory-related NDDs.
持续的炎症反应与各种神经退行性疾病（NDDs）有关。var. （CN），一种本土浆果，据报道具有多种有益健康的特性。然而，对 CN 种子的研究仍然有限。本研究的目的是评估乙醇种子提取物（CNSE）对 TNF-α炎症刺激的 BV-2 小鼠小胶质细胞的保护作用及其机制。通过 LC-MS 分析，在 CNSE 中发现了阿魏酸、奥瑞替辛、 Brassitin、鞣花酸和白杨素。首先，我们进行了分子对接，以阐明其对炎症相关机制的生物活性成分。结果表明，白杨素、奥瑞替辛和鞣花酸抑制 NF-κB 激活和 iNOS 功能，而白杨素和奥瑞替辛仅抑制 COX-2 功能。我们的细胞实验表明，用 CNSE（5、10 和 25μg/mL）预处理的细胞减少了纺锤形细胞的数量，而 TNF-α处理（10ng/mL）则高度观察到这种情况。CNSE 还阻断了 TNF-α、IL-1β 和 IL-6 mRNA 水平，并抑制了 BV-2 细胞培养物中 TNF-α和 IL-6 的释放。值得注意的是，CNSE 降低了与 NF-κB 结合活性抑制相关的 ERK、p38MAPK、p65 和 IκB-α的磷酸化形式。CNSE 明显诱导了 HO-1 蛋白的表达。我们的研究结果表明，CNSE 为预防炎症相关的 NDDs 提供了良好的潜力。
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