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小豆蔻明通过 TLR2、4-mTOR-自噬通路抑制颗粒物诱导的肺损伤。

Inhibitory functions of cardamonin against particulate matter-induced lung injury through TLR2,4-mTOR-autophagy pathways.

机构信息

College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University, Daegu 41566, Republic of Korea; Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.

School of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.

出版信息

Fitoterapia. 2020 Oct;146:104724. doi: 10.1016/j.fitote.2020.104724. Epub 2020 Sep 15.

DOI:10.1016/j.fitote.2020.104724
PMID:32946945
Abstract

Particulate matter with an aerodynamic diameter equal to or less than 2.5 μm (PM) is a form of air pollutant that causes significant lung damage when inhaled. Cardamonin, a flavone found in Alpinia katsumadai Heyata seeds, has been reported to have anti-inflammatory and anticoagulative activity. The aim of this study was to determine the protective effects of cardamonin on PM-induced lung injury. Mice were treated with cardamonin via tail-vein injection 30 min after the intratracheal instillation of PM. The results showed that cardamonin markedly reduced the pathological lung injury, lung wet/dry weight ratio, and hyperpermeability caused by PM. Cardamonin also significantly inhibited PM-induced myeloperoxidase (MPO) activity in lung tissue, decreased the levels of PM-induced inflammatory cytokines and effectively attenuated PM-induced increases in the number of lymphocytes in the bronchoalveolar lavage fluid (BALF). And, cardamonin increased the phosphorylation of mammalian target of rapamycin (mTOR) and dramatically suppressed the PM-stimulated expression of toll-like receptor 2 and 4 (TLR 2,4), MyD88, and the autophagy-related proteins LC3 II and Beclin 1. In conclusion, these findings indicate that cardamonin has a critical anti-inflammatory effect due to its ability to regulate both the TLR2,4-MyD88 and mTOR-autophagy pathways and may thus be a potential therapeutic agent against PM-induced lung injury.

摘要

粒径等于或小于 2.5μm 的颗粒物(PM)是一种空气污染物,吸入后会对肺部造成严重损害。小豆蔻明,一种在益智种子中发现的类黄酮,已被报道具有抗炎和抗凝活性。本研究旨在确定小豆蔻明对 PM 诱导的肺损伤的保护作用。小鼠在气管内滴注 PM 后 30 分钟通过尾静脉注射小豆蔻明进行治疗。结果表明,小豆蔻明显著减轻了 PM 引起的肺部病理损伤、肺湿/干重比和通透性增加。小豆蔻明还显著抑制了 PM 诱导的肺组织髓过氧化物酶(MPO)活性,降低了 PM 诱导的炎症细胞因子水平,并有效抑制了 PM 诱导的支气管肺泡灌洗液(BALF)中淋巴细胞数量的增加。而且,小豆蔻明增加了雷帕霉素靶蛋白(mTOR)的磷酸化,并显著抑制了 PM 刺激的 Toll 样受体 2 和 4(TLR 2,4)、MyD88 以及自噬相关蛋白 LC3 II 和 Beclin 1 的表达。总之,这些发现表明,小豆蔻明具有关键的抗炎作用,因为它能够调节 TLR2,4-MyD88 和 mTOR-自噬途径,因此可能是治疗 PM 诱导的肺损伤的潜在治疗剂。

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