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

Particulate matter with an aerodynamic diameter equal to or less than 2.5 μm (PM2.5) 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 PM2.5-induced lung injury. Mice were treated with cardamonin via tail-vein injection 30 min after the intratracheal instillation of PM2.5. The results showed that cardamonin markedly reduced the pathological lung injury, lung wet/dry weight ratio, and hyperpermeability caused by PM2.5. Cardamonin also significantly inhibited PM2.5-induced myeloperoxidase (MPO) activity in lung tissue, decreased the levels of PM2.5-induced inflammatory cytokines and effectively attenuated PM2.5-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 PM2.5-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 PM2.5-induced lung injury.

Lee W ，Hahn D ，Sim H ，Choo S ，Lee S ，Lee T ，Bae JS ... -  《-》

Inhibitory functions of maslinic acid on particulate matter-induced lung injury through TLR4-mTOR-autophagy pathways.

Particulate matter (PM), the collection of all liquid and solid particles suspended in air, includes both organic and inorganic particles, many of which are health-hazards. PM particles with a diameter equal to or less than 2.5 μm (PM2.5) is a form of air pollutant that causes significant lung damage when inhaled. Maslinic acid (MA) prevents oxidative stress and pro-inflammatory cytokine generation, but there is little information available regarding its role in PM-induced lung injury. Therefore, the purpose of this study was to determine the protective activity of MA against PM2.5-induced lung injury. The mice were divided into seven groups (n = 10 each): a mock control group, an MA control (0.8 mg/kg mouse body weight) group, an opted PM2.5 produced from diesel (10 mg/kg mouse body weight) group, a diesel PM2.5+MA (0.2, 0.4, 0.6, and 0.8 mg/kg mouse body weight) groups. Mice were treated with MA via tail-vein injection 30 min after the intratracheal instillation of a diesel PM2.5. Changes in the wet/dry weight ratio of the lung tissue, total protein/total cell and lymphocyte counts, inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), vascular permeability, and histology were monitored in diesel PM2.5-treated mice. The results showed that MA reduced pathological lung injury, the wet/dry weight ratio of the lung tissue, and hyperpermeability caused by diesel PM2.5. MA also inhibited diesel PM2.5-induced myeloperoxidase (MPO) activity in the lung tissue, decreased the levels of diesel PM2.5-induced inflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-1β, reduced nitric oxide (NO) and total protein in the BALF, and effectively attenuated diesel PM2.5-induced increases in the number of lymphocytes in the BALF. In addition, MA increased the protein phosphorylation of the mammalian target of rapamycin (mTOR) and dramatically suppressed diesel PM2.5-stimulated expression of toll-like receptor 4 (TLR4), MyD88, and the autophagy-related proteins LC3 II and Beclin 1. In conclusion, these findings indicate that MA has a critical anti-inflammatory effect due to its ability to regulate both the TLR4-MyD88 and mTOR-autophagy pathways and may thus be a potential therapeutic agent against diesel PM2.5-induced lung injury.

Jeong SY ，Kim J ，Park EK ，Baek MC ，Bae JS ... -  《-》

Biapenem as a Novel Insight into Drug Repositioning against Particulate Matter-Induced Lung Injury.

Lee W ，Baek MC ，Kim KM ，Bae JS ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

YiQiFuMai lyophilized injection attenuates particulate matter-induced acute lung injury in mice via TLR4-mTOR-autophagy pathway.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the serious diseases that are characterized by a severe inflammatory response of lung injuries and damage to the microvascular permeability, frequently resulting in death. YiQiFuMai (YQFM) lyophilized injection powder is a redeveloped preparation based on the well-known traditional Chinese medicine formula Sheng-Mai-San which is widely used in clinical practice in China, mainly for the treatment of microcirculatory disturbance-related diseases. However, there is little information about its role in ALI/ARDS. The aim of this study was to determine the protective effect of YQFM on particulate matter (PM)-induced ALI. The mice were intratracheally instilled with 50 mg/kg body weight of Standard Reference Material1648a (SRM1648a) in the PM-induced group. The mice in the YQFM group were given YQFM (three doses: 0.33, 0.67, and 1.34 g/kg) by tail vein injection 30 min after the intratracheal instillation of PM. The results showed that YQFM markedly reduced lung pathological injury and the lung wet/dry weight ratios induced by PM. Furthermore, we also found that YQFM significantly inhibited the PM-induced myeloperoxidase (MPO) activity in lung tissues, decreased the PM-induced inflammatory cytokines including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), reduced nitric oxide (NO) and total protein in bronchoalveolar lavage fluids (BALF), and effectively attenuated PM-induced increases lymphocytes in BALF. In addition, YQFM increased mammalian target of rapamycin (mTOR) phosphorylation and dramatically suppressed the PM-stimulated expression of toll-like receptor 4 (TLR4), MyD88, autophagy-related protein LC3Ⅱand Beclin 1 as well as autophagy. In conclusion, these findings indicate that YQFM had a critical anti-inflammatory effect due to its ability to regulate both TLR4-MyD88 and mTOR-autophagy pathways, and might be a possible therapeutic agent for PM-induced ALI.

Xia Y ，S D ，Jiang S ，Fan R ，Wang Y ，Wang Y ，Tang J ，Zhang Y ，He RL ，Yu B ，Kou J ... -  《-》

Therapeutic effects of hederacolchiside A1 on particulate matter-induced pulmonary injury.

Particulate matter (PM) comprises a hazardous mixture of inorganic and organic particles that carry health risks. Inhaling fine PM particles with a diameter of ≤2.5 μm (PM2.5) can promote significant lung damage. Hederacolchiside A1 (HA1) exhibits notable in vivo antitumor effects against various solid tumors. However, our understanding of its therapeutic potential for individuals with PM2.5-induced lung injuries remains limited. Here, we explored the protective properties of HA1 against lung damage caused by PM2.5 exposure. HA1 was administered to the mice 30 min after intratracheal tail vein injection of PM2.5. Various parameters, such as changes in lung tissue wet/dry (W/D) weight ratio, total protein/total cell ratio, lymphocyte counts, inflammatory cytokine levels in bronchoalveolar lavage fluid (BALF), vascular permeability, and histology, were assessed in mice exposed to PM2.5. Our data showed that HA1 mitigated lung damage, reduced the W/D weight ratio, and suppressed hyperpermeability caused by PM2.5 exposure. Moreover, HA1 effectively decreased plasma levels of inflammatory cytokines in those exposed to PM2.5, including tumor necrosis factor-α, interleukin-1β, and nitric oxide, while also lowering the total protein concentration in BALF and successfully alleviating PM2.5-induced lymphocytosis. Furthermore, HA1 significantly decreased the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation primary response (MyD) 88, and autophagy-related proteins LC3 II and Beclin 1 but increased the protein phosphorylation of the mammalian target of rapamycin (mTOR). The anti-inflammatory characteristics of HA1 highlights its potential as a promising therapeutic agent for mitigating PM2.5-induced lung injuries by modulating the TLR4-MyD88 and mTOR-autophagy pathways.

Cho S ，Choi HJ ，Song GY ，Bae JS ... -  《-》