白皮银莲花（Roth）O.Deg. 提取物通过调节 TNF/Akt/NF-κB 通路发挥抗炎作用。
Biancaea decapetala (Roth) O.Deg. extract exerts an anti-inflammatory effect by regulating the TNF/Akt/NF-κB pathway.
机构信息
State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Beijing Road 9, Guiyang 550004, PR China; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, PR China.
State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Beijing Road 9, Guiyang 550004, PR China.
出版信息
Phytomedicine. 2023 Oct;119:154983. doi: 10.1016/j.phymed.2023.154983. Epub 2023 Jul 17.
BACKGROUND
Biancaea decapetala (Roth) O.Deg. (Fabaceae) is used to treat colds, fever, and rheumatic pain caused by inflammation. However, the mechanism underlying its anti-inflammatory properties remains unclear.
PURPOSE
This study aimed to evaluate the anti-inflammatory activity of Biancaea decapetala extract (BDE) in vitro and in vivo and explore the possible underlying mechanism and potential targets.
METHODS
The release of nitric oxide (NO) and inflammatory cytokines in LPS-stimulated RAW264.7 cells and rats were measured using Griess reagent and enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining was employed to examine the pathology of animal tissues. Transcriptome analysis was performed to screen the pathways related to BDE-mediated inhibition of inflammation, and the expression of related proteins was measured using real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, ELISA, and immunofluorescence methods. Surface Plasmon Resonance (SPR) and the Drug Affinity Reaction Target Stability (DARTS) method were used to verify whether BDE binds to TNF-α target protein, while a L929 cell model and NF-κB gene reporter systematic method were used to investigate the inhibitory effect of BDE on the activity of TNF-α protein.
RESULTS
BDE inhibited the expression of TNF-α, IL-1β, IL-6, and NO in RAW264.7 cells and rats, and improved the pathological changes in lung tissue. RNA-seq showed that BDE may regulate the TNF/Akt/NF-κB pathway to inhibit inflammation onset. BDE significantly downregulated the mRNA expression of TNF-α, IL-6, IL-1β, and that of relevant proteins, including TNF-α, p-p65, p-Akt, p-IκBα. Furthermore, BDE inhibited the nuclear translocation of NF-κB (p65) and the activation of the Akt pathway by SC79. The L929 cell model, luciferase reporter gene analysis, DARTS, and SPR experiments showed that BDE may bind to TNF-α and inhibit the TNF-α-NF-κB pathway.
CONCLUSION
BDE may target TNF-α to inhibit the TNF/Akt/NF-κB pathway, thereby attenuating inflammation. These findings reveal the anti-inflammatory effects and mechanisms of BDE and provide a theoretical basis for the further development and utilization of BDE.
背景
Biancaea decapetala (Roth) O.Deg.（豆科）用于治疗感冒、发热和炎症引起的风湿痛。然而，其抗炎特性的机制尚不清楚。
目的
本研究旨在评估 Biancaea decapetala 提取物（BDE）在体外和体内的抗炎活性，并探讨其可能的作用机制和潜在靶点。
方法
采用 Griess 试剂和酶联免疫吸附试验（ELISA）测定 LPS 刺激的 RAW264.7 细胞和大鼠中一氧化氮（NO）和炎症细胞因子的释放。采用苏木精和伊红（H&E）染色观察动物组织的病理学变化。通过转录组分析筛选与 BDE 介导的炎症抑制相关的途径，并通过实时定量聚合酶链反应（RT-qPCR）、Western blot、ELISA 和免疫荧光方法测量相关蛋白的表达。表面等离子体共振（SPR）和药物亲和反应靶标稳定性（DARTS）方法用于验证 BDE 是否与 TNF-α 靶蛋白结合，而 L929 细胞模型和 NF-κB 基因报告系统方法用于研究 BDE 对 TNF-α 蛋白活性的抑制作用。
结果
BDE 抑制了 RAW264.7 细胞和大鼠中 TNF-α、IL-1β、IL-6 和 NO 的表达，并改善了肺组织的病理变化。RNA-seq 显示，BDE 可能通过调节 TNF/Akt/NF-κB 通路来抑制炎症的发生。BDE 显著下调了 TNF-α、IL-6、IL-1β 的 mRNA 表达及其相关蛋白，包括 TNF-α、p-p65、p-Akt、p-IκBα。此外，BDE 抑制了 NF-κB（p65）的核转位和 Akt 通路的激活。L929 细胞模型、荧光素酶报告基因分析、DARTS 和 SPR 实验表明，BDE 可能与 TNF-α 结合并抑制 TNF-α-NF-κB 通路。
结论
BDE 可能通过靶向 TNF-α 抑制 TNF/Akt/NF-κB 通路，从而减轻炎症。这些发现揭示了 BDE 的抗炎作用和机制，为进一步开发和利用 BDE 提供了理论依据。
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