Yindan Jiedu granules exhibit anti-inflammatory effect in patients with novel Coronavirus disease (COVID-19) by suppressing the NF-κB signaling pathway.
Yindan Jiedu granules exhibit anti-inflammatory effect in patients with novel Coronavirus disease (COVID-19) by suppressing the NF-κB signaling pathway.
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DOI：
10.1016/j.phymed.2021.153784
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Feng Y;Zhu B;Liu Y;Liu Y;Zhou G;Yang L;Liu L;Ren J;Hou Y;Yu H;Meng P;Jiang Y;Wang X
2019 年冠状病毒病 (COVID-19) 是一种大流行病，已在全球范围内造成大量死亡。炎症因素可能在 COVID-19 的进展中发挥重要作用。银丹解毒颗粒（YDJDG）可以抑制COVID-19的进展，但相关机制尚不清楚。评估YDJDG对COVID-19的治疗效果并探讨其潜在机制。我们招募了 262 名参与者，并使用一对一倾向评分匹配 (PSM) 将 97 名患者随机分配到 YDJDG 组和对照组。观察临床效果并测定血清炎症和免疫指标。通过预测和确定已识别化合物的靶标，建立了YDJDG的靶标网络模型。使用高效液相色谱-串联质谱 (HPLC-MS/MS) 和分子对接对 YDJDG 提取物的主要成分进行鉴定和评估。此外，还研究了YDJDG的抗炎作用及其具体的生物学作用机制。 PSM后结果显示，与对照组相比，YDJDG组急性肺部渗出性病灶消散时间更短（p < 0.0001），病毒核酸转阴时间更短（p < 0.01），血清淀粉样蛋白A水平和红细胞沉降率下降更快（p < 0.0001），CD4+T细胞上升率更高 计数（p = 0.0155）。通过重叠 YDJDG 和 COVID-19 的基因，确定了 213 个共同靶向基因。 Metascape富集分析显示，NF-κB通路中有25个基因显着富集，MS分析证实这些基因主要是木犀草素、槲皮素和山奈酚的靶标。分子对接表明，3种化合物的配体与NF-κB p65和IκBα有很强的相互作用。在体内，YDJDG 显着保护动物免受脂多糖 (LPS) 诱导的急性肺损伤 (ALI)，降低肺湿/干重比、ALI 评分和肺组织学损伤。在 LPS 处理的 RAW264.7 细胞中，YDJDG 抑制 NF-κB p65 的核转位。在体内和体外，YDJDG 通过抑制炎症细胞因子（IL-6、IL-1β 和 TNF-α）的产生发挥抗炎作用。这些作用伴随着 NF-κB 激活和 IκBα 磷酸化的抑制。 YDJDG 可以通过靶向 NF-κB 通路抑制炎症，从而缩短 COVID-19 病程并延缓其进展。
Coronavirus disease 2019 (COVID-19) is a pandemic that has caused a high number of deaths worldwide. Inflammatory factors may play important roles in COVID-19 progression. Yindan Jiedu granules (YDJDG) can inhibit the progression of COVID-19, but the associated mechanism is unclear. To evaluate the therapeutic effects of YDJDG on COVID-19 and explore its underlying mechanism. We recruited 262 participants and randomly assigned 97 patients each to the YDJDG and control groups using one-to-one propensity score matching (PSM). Clinical effects were observed and serum inflammatory and immune indicators were measured. The target network model of YDJDG was established by predicting and determining the targets of identified compounds. The main constituents of the YDJDG extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. Besides, the anti-inflammatory effects of YDJDG and its specific biological mechanism of action were studied. After PSM, the results showed that compared with the control group, the YDJDG group had a shorter time of dissipation of acute pulmonary exudative lesions (p < 0.0001), shorter time to negative conversion of viral nucleic acid (p < 0.01), more rapid decrease in serum amyloid A level and erythrocyte sedimentation rate (p < 0.0001), and a higher rate of increase in CD4+T cell count (p = 0.0155). By overlapping the genes of YDJDG and COVID-19, 213 co-targeted genes were identified. Metascape enrichment analysis showed that 25 genes were significantly enriched in the NF-κB pathway, which were mainly targets of luteolin, quercetin, and kaempferol as confirmed by MS analysis. Molecular docking revealed that the ligands of three compounds had strong interaction with NF-κB p65 and IκBα. In vivo, YDJDG significantly protected animals from lipopolysaccharide (LPS)-induced acute lung injury (ALI), decreasing the lung wet/dry weight ratio, ALI score, and lung histological damage. In LPS-treated RAW264.7 cells, YDJDG suppressed nuclear translocation of NF-κB p65. In vivo and in vitro, YDJDG exerted anti-inflammatory effects by inhibiting the production of inflammatory cytokines (IL-6, IL-1β, and TNF-α). These effects were accompanied by the inhibition of NF-ĸB activation and IκBα phosphorylation. YDJDG may shorten the COVID-19 course and delay its progression by suppressing inflammation via targeting the NF-κB pathway.
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影响因子：
5.8
作者：
Hariharan A;Hakeem AR;Radhakrishnan S;Reddy MS;Rela M
通讯作者：
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5.7
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通讯作者：
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影响因子：
3
作者：
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影响因子：
39.3
作者：
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通讯作者：
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影响因子：
24.3
作者：
Silva, P. L.;Garcia, C. S. N. B.;Rocco, P. R. M.
通讯作者：
Rocco, P. R. M.