Platycodon grandiflorus decoction attenuates lipopolysaccharide-induced acute lung injury via the PI3K/Akt/NF-κB pathway

脂多糖 PI3K/AKT/mTOR通路 汤剂 NF-κB 蛋白激酶B 药理学 医学 传统医学 化学 信号转导 炎症 内科学 生物化学
作者
Zihua Xuan,Hongyan Wu,Shuting Zhang,Yajuan Wang,Ming Chen,Shuangying Gui,Jutao Wang,Yang Yu
出处
期刊:Journal of Functional Foods [Elsevier BV]
卷期号:121: 106448-106448 被引量:1
标识
DOI:10.1016/j.jff.2024.106448
摘要

Acute lung injury (ALI) is a diffuse inflammatory lung injury caused by various internal and external causal elements. In addition to its medical benefits, PGD can also be used to steep tea, which has the effect of lung-moistening and expectotant, and has been demonstrated to exert a protective effect against ALI. However, its exact mechanism of action is unknown. C57BL/6 mice were divided into different groups to study the therapeutic effects of different doses of PGD and dexamethasone. The chemical composition of PGD was analyzed using UPLC-Q-TOF-MS/MS and network pharmacology was used to identify its active components and pathways. In vitro molecular docking and in vivo pharmacodynamic experiments were conducted to further investigate its mechanism of action. In vivo experiments demonstrated that PGD mitigated histopathological alterations, reduced the total leukocyte count, total protein concentration, and suppressed levels of IL-6, TNF-α, and IL-1β in lung tissue. Additionally, PGD decreased levels of IL-6, TNF-α, and IL-1β in BALF, as well as levels of IL-6 and TNF-α in serum. Network pharmacology analysis revealed GAPDH, TP53, AKT1, ALB, TNF, IL-6, VEGFA, EGFR, STAT3, and JUN as core targets, with the key pathways identified as PI3K/AKT and NF-κB. Additional western blotting and qPCR further confirmed that PGD significantly reduced the ratios of p-PI3K/PI3K, p-AKT/AKT, and p-NF-κB/NF-κB, as well as the mRNA levels of PI3K, AKT, and NF-κB. PGD shows promise in alleviating ALI by modulating the PI3K/AKT/NF-κB signaling pathway, suggesting its potential as a targeted therapeutic approach for LPS-induced ALI.
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