桔梗煎剂通过PI3K/Akt/NF-κB途径减轻脂多糖诱导的急性肺损伤

IF 3.8 2区 农林科学 Q2 FOOD SCIENCE & TECHNOLOGY Journal of Functional Foods Pub Date : 2024-09-15 DOI:10.1016/j.jff.2024.106448
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引用次数: 0

摘要

急性肺损伤(ALI)是由各种内外因引起的弥漫性肺部炎症损伤。PGD 除具有医疗作用外,还可用于沏茶,具有润肺和祛痰的功效,已被证实对 ALI 有保护作用。然而,其确切的作用机制尚不清楚。将 C57BL/6 小鼠分为不同组,研究不同剂量的 PGD 和地塞米松的治疗效果。利用 UPLC-Q-TOF-MS/MS 分析了 PGD 的化学成分,并利用网络药理学确定了其活性成分和途径。为了进一步研究其作用机制,还进行了体外分子对接和体内药效学实验。体内实验表明,PGD 可减轻组织病理学改变,降低白细胞总数和总蛋白浓度,抑制肺组织中 IL-6、TNF-α 和 IL-1β 的水平。此外,PGD 还能降低 BALF 中 IL-6、TNF-α 和 IL-1β 的水平,以及血清中 IL-6 和 TNF-α 的水平。网络药理学分析显示,GAPDH、TP53、AKT1、ALB、TNF、IL-6、VEGFA、表皮生长因子受体、STAT3 和 JUN 为核心靶点,关键通路为 PI3K/AKT 和 NF-κB。其他的 Western 印迹和 qPCR 进一步证实,PGD 能显著降低 p-PI3K/PI3K、p-AKT/AKT 和 p-NF-κB/NF-κB 的比率,以及 PI3K、AKT 和 NF-κB 的 mRNA 水平。PGD有望通过调节PI3K/AKT/NF-κB信号通路缓解ALI,这表明它有可能成为LPS诱导的ALI的靶向治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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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来源期刊
Journal of Functional Foods
Journal of Functional Foods FOOD SCIENCE & TECHNOLOGY-
CiteScore
9.60
自引率
1.80%
发文量
428
审稿时长
76 days
期刊介绍: Journal of Functional Foods continues with the same aims and scope, editorial team, submission system and rigorous peer review. We give authors the possibility to publish their top-quality papers in a well-established leading journal in the food and nutrition fields. The Journal will keep its rigorous criteria to screen high impact research addressing relevant scientific topics and performed by sound methodologies. The Journal of Functional Foods aims to bring together the results of fundamental and applied research into healthy foods and biologically active food ingredients. The Journal is centered in the specific area at the boundaries among food technology, nutrition and health welcoming papers having a good interdisciplinary approach. The Journal will cover the fields of plant bioactives; dietary fibre, probiotics; functional lipids; bioactive peptides; vitamins, minerals and botanicals and other dietary supplements. Nutritional and technological aspects related to the development of functional foods and beverages are of core interest to the journal. Experimental works dealing with food digestion, bioavailability of food bioactives and on the mechanisms by which foods and their components are able to modulate physiological parameters connected with disease prevention are of particular interest as well as those dealing with personalized nutrition and nutritional needs in pathological subjects.
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