PDF(Pubmed)
Abstract：
UNASSIGNED: Lung inflammation occurs in many lung diseases, but has limited effective therapeutics. Ginseng and its derivatives have anti-inflammatory effects, but their unstable physicochemical and metabolic properties hinder their application in the treatment. Panaxadiol (PD) is a stable saponin among ginsenosides. Inhalation administration may solve these issues, and the specific mechanism of action needs to be studied.
UNASSIGNED: A mouse model of lung inflammation induced by lipopolysaccharide (LPS), an in vitro macrophage inflammation model, and a coculture model of epithelial cells and macrophages were used to study the effects and mechanisms of inhalation delivery of PD. Pathology and molecular assessments were used to evaluate efficacy. Transcriptome sequencing was used to screen the mechanism and target. Finally, the efficacy and mechanism were verified in a human BALF cell model.
UNASSIGNED: Inhaled PD reduced LPS-induced lung inflammation in mice in a dose-dependent manner, including inflammatory cell infiltration, lung tissue pathology, and inflammatory factor expression. Meanwhile, the dose of inhalation was much lower than that of intragastric administration under the same therapeutic effect, which may be related to its higher bioavailability and superior pharmacokinetic parameters. Using transcriptome analysis and verification by a coculture model of macrophage and epithelial cells, we found that PD may act by inhibiting TNFA/TNFAR and IL7/IL7R signaling to reduce macrophage inflammatory factor-induced epithelial apoptosis and promote proliferation.
UNASSIGNED: PD inhalation alleviates lung inflammation and pathology by inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells. PD may be a novel drug for the clinical treatment of lung inflammation.
UNASSIGNED: A mouse model of lung inflammation induced by lipopolysaccharide (LPS), an in vitro macrophage inflammation model, and a coculture model of epithelial cells and macrophages were used to study the effects and mechanisms of inhalation delivery of PD. Pathology and molecular assessments were used to evaluate efficacy. Transcriptome sequencing was used to screen the mechanism and target. Finally, the efficacy and mechanism were verified in a human BALF cell model.
UNASSIGNED: Inhaled PD reduced LPS-induced lung inflammation in mice in a dose-dependent manner, including inflammatory cell infiltration, lung tissue pathology, and inflammatory factor expression. Meanwhile, the dose of inhalation was much lower than that of intragastric administration under the same therapeutic effect, which may be related to its higher bioavailability and superior pharmacokinetic parameters. Using transcriptome analysis and verification by a coculture model of macrophage and epithelial cells, we found that PD may act by inhibiting TNFA/TNFAR and IL7/IL7R signaling to reduce macrophage inflammatory factor-induced epithelial apoptosis and promote proliferation.
UNASSIGNED: PD inhalation alleviates lung inflammation and pathology by inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells. PD may be a novel drug for the clinical treatment of lung inflammation.
摘要：
■肺部炎症发生在许多肺部疾病中，但有效的治疗方法有限。人参及其衍生物具有抗炎作用，但是它们不稳定的物理化学和代谢特性阻碍了它们在治疗中的应用。人参二醇(PD)是人参皂苷中一种稳定的皂苷。吸入管理可以解决这些问题，具体的作用机制有待研究。
■脂多糖（LPS）诱导的小鼠肺部炎症模型，体外巨噬细胞炎症模型，并利用上皮细胞和巨噬细胞共培养模型研究吸入PD的作用和机制。病理学和分子评估用于评价疗效。转录组测序用于筛选机制和靶标。最后,在人BALF细胞模型中验证了其功效和机制。
■吸入PD以剂量依赖的方式减少了LPS诱导的小鼠肺部炎症，包括炎症细胞浸润,肺组织病理学，和炎症因子的表达。同时,在相同的治疗效果下，吸入剂量远低于灌胃给药，这可能与其较高的生物利用度和优越的药代动力学参数有关。使用转录组分析并通过巨噬细胞和上皮细胞的共培养模型进行验证，我们发现PD可能通过抑制TNFA/TNFAR和IL7/IL7R信号通路,减少巨噬细胞炎症因子诱导的上皮凋亡,促进细胞增殖。
■PD吸入通过抑制巨噬细胞和上皮细胞之间的TNFA/TNFAR和IL7/IL7R信号传导减轻肺部炎症和病理。PD可能是临床治疗肺部炎症的新药。
■脂多糖（LPS）诱导的小鼠肺部炎症模型，体外巨噬细胞炎症模型，并利用上皮细胞和巨噬细胞共培养模型研究吸入PD的作用和机制。病理学和分子评估用于评价疗效。转录组测序用于筛选机制和靶标。最后,在人BALF细胞模型中验证了其功效和机制。
■吸入PD以剂量依赖的方式减少了LPS诱导的小鼠肺部炎症，包括炎症细胞浸润,肺组织病理学，和炎症因子的表达。同时,在相同的治疗效果下，吸入剂量远低于灌胃给药，这可能与其较高的生物利用度和优越的药代动力学参数有关。使用转录组分析并通过巨噬细胞和上皮细胞的共培养模型进行验证，我们发现PD可能通过抑制TNFA/TNFAR和IL7/IL7R信号通路,减少巨噬细胞炎症因子诱导的上皮凋亡,促进细胞增殖。
■PD吸入通过抑制巨噬细胞和上皮细胞之间的TNFA/TNFAR和IL7/IL7R信号传导减轻肺部炎症和病理。PD可能是临床治疗肺部炎症的新药。
