Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Therapeutic Effects of (+)-Afzelechin on Particulate Matter-Induced Pulmonary Injury

  • Sanghee Cho (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Yun Jin Park (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Jong-Sup Bae (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)
  • Received : 2023.10.30
  • Accepted : 2023.11.15
  • Published : 2024.01.01
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Abstract

Particulate matter (PM) constitutes a hazardous blend of organic and inorganic particles that poses health risks. Inhalation of fine airborne PM with a diameter of ≤ 2.5 ㎛ (PM2.5) can lead to significant lung impairments. (+)-afzelechin (AZC), a natural compound sourced from Bergenia ligulata, boasts a range of attributes, including antioxidant, antimicrobial, anticancer, and cardiovascular effects. However, knowledge about the therapeutic potential of AZC for patients with PM2.5-induced lung injuries remains limited. Thus, in this study, we investigated the protective attributes of AZC against lung damage caused by PM2.5 exposure. AZC was administered to the mice 30 min after intratracheal instillation of PM2.5. Various parameters, such as changes in lung tissue wet/dry (W/D) weight ratio, total protein/total cell ratio, lymphocyte counts, levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF), vascular permeability, and histology, were evaluated in mice exposed to PM2.5. Data demonstrated that AZC mitigated lung damage, reduced W/D weight ratio, and curbed hyperpermeability induced by PM2.5 exposure. Furthermore, AZC effectively lowered plasma levels of inflammatory cytokines produced by PM2.5 exposure. It reduced the total protein concentration in BALF and successfully alleviated PM2.5-induced lymphocytosis. Additionally, AZC substantially diminished the expression levels of Toll-like receptors 4 (TLR4), MyD88, and autophagy-related proteins LC3 II and Beclin 1. In contrast, it elevated the protein phosphorylation of the mammalian target of rapamycin (mTOR). Consequently, the anti-inflammatory attribute of AZC positions it as a promising therapeutic agent for mitigating PM2.5-induced lung injuries by modulating the TLR4-MyD88 and mTOR-autophagy pathways.

Keywords

Acknowledgement

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020R1A2C1004131).

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