Department of Pediatric Internal Medicine, Juancheng People's Hospital, Heze, Shandong, China.
Department of Pediatric, Heze Municipal Hospital, Heze, Shandong, China.
J Cell Biochem. 2019 Dec;120(12):19764-19774. doi: 10.1002/jcb.29282. Epub 2019 Jul 11.
Notoginsenoside R1 (NGR1) is a neoteric phytoestrogen extracted from Panax notoginseng, and possesses comprehensive pharmacological functions in multitudinous ailments. But, whether NGR1 is utilized in neonatal pneumonia is not clear. This research study aspired to disclose the protective activity of NGR1 in neonatal pneumonia. WI-38 cells were co-stimulated with NGR1 and lipopolysaccharide (LPS, 10 ng/mL), CCK-8 and flow cytometry assays were implemented for cell viability and apoptosis assessment. Real-time quantitative plymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and Western blot analysis were executed for inflammatory cytokine determination. MicroRNA-181a (miR-181a) expression was evaluated through RT-qPCR, simultaneously, the impact of miR-181a was estimated in NGR1 and LPS co-managed cells. Dual luciferase report assay was performed to disclose the relation between miR-181a and Toll-like receptor 4 (TLR4). The nuclear factor-κB (NF-κB) and TAK1/JNK pathways were ultimately appraised. We found that NGR1 decreased cell viability, evoked apoptosis and impeded interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) expression and secretions in LPS-managed WI-38 cells. MiR-181a expression was enhanced by NGR1, and miR-181a inhibition inverted the impacts of NGR1 in LPS-managed WI-38 cells. Besides, TLR4 was predicted to be a firsthand direct target of miR-181a. Furthermore, NGR1 hindered NF-κB and TAK1/JNK pathways through modulating TLR4. These discoveries disclosed the fact that NGR1 protected WI-38 cells against LPS-triggered injury via adjusting the miR-181a/TLR4 and NF-κB and TAK1/JNK pathways.
三七总皂苷 R1（NGR1）是从三七中提取的新型植物雌激素，具有多种疾病的综合药理作用。但是，NGR1 是否用于新生儿肺炎尚不清楚。本研究旨在揭示 NGR1 在新生儿肺炎中的保护作用。用 NGR1 和脂多糖（LPS，10ng/ml）共同刺激 WI-38 细胞，通过 CCK-8 和流式细胞术检测细胞活力和细胞凋亡。实时定量聚合酶链反应（RT-qPCR）、酶联免疫吸附试验（ELISA）和 Western blot 分析用于测定炎症细胞因子。通过 RT-qPCR 评估 microRNA-181a（miR-181a）的表达，同时评估 miR-181a 在 NGR1 和 LPS 共同处理的细胞中的作用。双荧光素酶报告实验揭示了 miR-181a 与 Toll 样受体 4（TLR4）之间的关系。最终评估了核因子-κB（NF-κB）和 TAK1/JNK 通路。我们发现 NGR1 降低了 LPS 处理的 WI-38 细胞的细胞活力，诱导了细胞凋亡，并抑制了白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达和分泌。NGR1 增强了 miR-181a 的表达，miR-181a 抑制逆转了 NGR1 在 LPS 处理的 WI-38 细胞中的作用。此外，TLR4 被预测为 miR-181a 的直接靶标之一。此外，NGR1 通过调节 TLR4 抑制了 NF-κB 和 TAK1/JNK 通路。这些发现表明，NGR1 通过调节 miR-181a/TLR4 和 NF-κB 和 TAK1/JNK 通路来保护 WI-38 细胞免受 LPS 触发的损伤。
