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

Abstract

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.

• Authors: Yuanli Xia, Dolgor S, Siyu Jiang, Ruiping Fan, Yumeng Wang, Yuwei Wang, Jiahui Tang, Yuanyuan Zhang, Rong Lucy He, Boyang Yu, Junping Kou
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 108 Pg. 906-913 (Dec 2018) ISSN: 1950-6007 [Electronic] France
• PMID: 30372902 (Publication Type: Journal Article)
• Copyright: Copyright © 2018. Published by Elsevier Masson SAS.

Chemical References

• Cytokines
• Drugs, Chinese Herbal
• Particulate Matter
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• yi-qi-fu-mai
• Peroxidase
• mTOR protein, mouse
• TOR Serine-Threonine Kinases

Topics

• Acute Lung Injury (chemically induced, drug therapy, metabolism)
• Animals
• Autophagy (drug effects)
• Bronchoalveolar Lavage Fluid (chemistry)
• China
• Cytokines (metabolism)
• Drugs, Chinese Herbal (pharmacology)
• Injections (methods)
• Lung (drug effects, metabolism)
• Medicine, Chinese Traditional (methods)
• Mice
• Particulate Matter (pharmacology)
• Peroxidase (metabolism)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)
• Toll-Like Receptor 4 (metabolism)