Inhalation of panaxadiol alleviates lung inflammation via inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells

IF 6.8 2区 医学 Q1 CHEMISTRY, MEDICINAL Journal of Ginseng Research Pub Date : 2024-01-01 DOI:10.1016/j.jgr.2023.09.002
Yifan Wang , Hao Wei , Zhen Song , Liqun Jiang , Mi Zhang , Xiao Lu , Wei Li , Yuqing Zhao , Lei Wu , Shuxian Li , Huijuan Shen , Qiang Shu , Yicheng Xie
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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

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通过抑制巨噬细胞和上皮细胞之间的 TNFA/TNFAR 和 IL7/IL7R 信号传递,吸入三七醇可缓解肺部炎症
背景许多肺部疾病都会引发肺部炎症,但有效的治疗方法却很有限。人参及其衍生物具有抗炎作用,但其不稳定的理化和代谢特性阻碍了它们在治疗中的应用。三七二醇(Panaxadiol,PD)是人参皂甙中一种稳定的皂甙。方法采用脂多糖(LPS)诱导的小鼠肺部炎症模型、体外巨噬细胞炎症模型以及上皮细胞和巨噬细胞共培养模型来研究吸入给药 PD 的作用和机制。病理学和分子评估用于评估疗效。转录组测序用于筛选机制和靶点。结果吸入 PD 能以剂量依赖的方式减轻 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表达。同时,在相同疗效下,吸入剂量远低于胃内给药,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。通过转录组分析和巨噬细胞与上皮细胞的共培养模型验证,我们发现 PD 可通过抑制 TNFA/TNFAR 和 IL7/IL7R 信号转导,减少巨噬细胞炎症因子诱导的上皮细胞凋亡,促进上皮细胞增殖。PD可能是临床治疗肺部炎症的一种新型药物。
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来源期刊
Journal of Ginseng Research
Journal of Ginseng Research CHEMISTRY, MEDICINAL-INTEGRATIVE & COMPLEMENTARY MEDICINE
CiteScore
11.40
自引率
9.50%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Journal of Ginseng Research (JGR) is an official, open access journal of the Korean Society of Ginseng and is the only international journal publishing scholarly reports on ginseng research in the world. The journal is a bimonthly peer-reviewed publication featuring high-quality studies related to basic, pre-clinical, and clinical researches on ginseng to reflect recent progresses in ginseng research. JGR publishes papers, either experimental or theoretical, that advance our understanding of ginseng science, including plant sciences, biology, chemistry, pharmacology, toxicology, pharmacokinetics, veterinary medicine, biochemistry, manufacture, and clinical study of ginseng since 1976. It also includes the new paradigm of integrative research, covering alternative medicinal approaches. Article types considered for publication include review articles, original research articles, and brief reports. JGR helps researchers to understand mechanisms for traditional efficacy of ginseng and to put their clinical evidence together. It provides balanced information on basic science and clinical applications to researchers, manufacturers, practitioners, teachers, scholars, and medical doctors.
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