Department of Respiratory Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Chongqing Key Laboratory of Pediatrics, Chongqing, PR China.
Department of Respiratory Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, PR China.
Int Immunopharmacol. 2020 Nov;88:106860. doi: 10.1016/j.intimp.2020.106860. Epub 2020 Aug 6.
BACKGROUD: Panax notoginseng saponin R1 (PNS-R1) is one of the most important chemical monomers derived from the panax notoginseng, and our previous study found that PNS-R1 reduced glucocorticoid-induced apoptosis in asthmatic airway epithelial cells. Thus, in this study, we explored the effects of the PNS-R1 on inflammation of allergic asthma. METHODS: The asthmatic mice were administered 15 mg/kg PNS-R1 by intraperitoneal injection three days before sensitized to OVA. The effects of PNS-R1 on asthmatic mice were detected by airway hyperresponsiveness, inflammation, mucus hypersecretion and inflammatory cytokines such as interleukin (IL)-13, IL-4, IL-5, IL-8 and tumor necrosis factor (TNF)-α were studied. We also treated human bronchial epithelial cells (16HBE) with house dust mites (HDM) and then detected the secretion of cellular inflammatory factors (IL-13 and TNF-α). Western blot and immunofluorescence were used to examine the effect of PNS-R1 on TNF-α/NF-κB pathway. TNF-α/NF-κB/IKK signal pathway activator was used in PNS-R1-treated asthmatic mice. RESULTS: PNS-R1 significantly reduced the airway inflammatory, mucus secretion and hyperresponsiveness in asthma model. It also reduced the levels of IL-13, IL-4, IL-5 and IL-8 in bronchoalveolar lavage fluid (BALF) and IgE and OVA-specific IgE in serum for asthma mice. PNS-R1 reduced IL-13 and TNF-α secretion in HDM-treated 16HBE cells. In addition, PNS-R1 suppressed TNF-α/NF-κB pathway in both asthmatic mice and 16HBE. Activation of NF-kB pathway reversed the therapeutic effect of PNS-R1 on asthmatic mice. CONCLUSION: The results indicated that PNS-R1 effectively suppresses allergic airway inflammation of asthma partly through TNF-α/NF-κB pathway. PNS-R1 may play a potential role in allergic asthma treatment in the future.
背景：三七总皂苷 R1（PNS-R1）是从三七中提取的最重要的化学单体之一，我们之前的研究发现 PNS-R1 可减少糖皮质激素诱导的哮喘气道上皮细胞凋亡。因此，在本研究中，我们探讨了 PNS-R1 对过敏性哮喘炎症的影响。
方法：哮喘小鼠在致敏 OVA 前 3 天腹腔注射 15mg/kg PNS-R1。通过气道高反应性、炎症、黏液分泌过度和白细胞介素（IL）-13、IL-4、IL-5、IL-8 和肿瘤坏死因子（TNF）-α 等炎症细胞因子检测 PNS-R1 对哮喘小鼠的作用。我们还用屋尘螨（HDM）处理人支气管上皮细胞（16HBE），然后检测细胞炎症因子（IL-13 和 TNF-α）的分泌。用 Western blot 和免疫荧光法检测 PNS-R1 对 TNF-α/NF-κB 通路的影响。用 TNF-α/NF-κB/IKK 信号通路激活剂处理 PNS-R1 治疗的哮喘小鼠。
结果：PNS-R1 显著减轻哮喘模型中的气道炎症、黏液分泌和高反应性，降低哮喘小鼠支气管肺泡灌洗液（BALF）中 IL-13、IL-4、IL-5 和 IL-8 水平以及血清中 IgE 和 OVA 特异性 IgE。PNS-R1 降低了 HDM 处理的 16HBE 细胞中 IL-13 和 TNF-α 的分泌。此外，PNS-R1 抑制了哮喘小鼠和 16HBE 中的 TNF-α/NF-κB 通路。NF-κB 通路的激活逆转了 PNS-R1 对哮喘小鼠的治疗作用。
结论：结果表明，PNS-R1 通过 TNF-α/NF-κB 通路有效抑制哮喘的过敏性气道炎症。PNS-R1 可能在未来对过敏性哮喘的治疗发挥潜在作用。
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