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.

中文翻译：

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三七皂苷 R1 调节 TNF-α/NF-κB 信号传导并减轻哮喘中的过敏性气道炎症。

背景

三七皂苷R1 （ PNS-R1）是三七衍生的最重要的化学单体之一，我们之前的研究发现PNS-R1减少了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

在对 OVA 致敏前三天，通过腹膜内注射给予哮喘小鼠 15 mg/kg PNS-R1。通过气道高反应性、炎症、粘液分泌过多和炎性细胞因子如白细胞介素（IL）-13、IL-4、IL-5、IL-8和肿瘤坏死因子（TNF）检测PNS-R1对哮喘小鼠的影响- α 进行了研究。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。使用蛋白质印迹和免疫荧光检测 PNS-R1 对 TNF-α/NF-κB 通路的影响。TNF-α/NF-κB/IKK 信号通路激活剂用于 PNS-R1 治疗的哮喘小鼠。

结果

PNS-R1显着降低哮喘模型的气道炎症、粘液分泌和高反应性。它还降低了哮喘小鼠支气管肺泡灌洗液 (BALF) 中 IL-13、IL-4、IL-5 和 IL-8 以及血清中 IgE 和 OVA 特异性 IgE 的水平。PNS-R1 减少了 HDM 处理的 16HBE 细胞中 IL-13 和 TNF-α 的分泌。此外，PNS-R1 抑制哮喘小鼠和 16HBE 的 TNF-α/NF-κB 通路。NF-kB 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部分通过TNF-α/NF-κB通路有效抑制哮喘过敏性气道炎症。PNS-R1未来可能在过敏性哮喘治疗中发挥潜在作用。