2. Academic Validation
  3. Gaylussacin, a stilbene glycoside, inhibits chronic obstructive pulmonary disease in mice

Gaylussacin, a stilbene glycoside, inhibits chronic obstructive pulmonary disease in mice

  • Redox Biol. 2025 Jun 26:85:103744. doi: 10.1016/j.redox.2025.103744.
Hye-Young Min 1,  Jeong Yeon Sim 2,  Jee Hwan Ahn 3,  Nae-Won Kang 2,  Hye-Jin Boo 4,  Jina Kim 5,  Na-Young Yu 2,  Marta Bottacin 2,  Jungmoo Huh 6,  Choon-Sik Park 7,  Jong-Sook Park 7,  Suckchang Hong 8,  Sungyong You 5,  Dae-Duk Kim 9,  Ho-Young Lee 10
Affiliations

Affiliations

  • 1 Natural Products Research Institute, Seoul National University, Seoul, 08826, Republic of Korea; College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.
  • 2 College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.
  • 3 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.
  • 4 College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea; Department of Histology, College of Medicine, Jeju National University, Jeju, 63243, Republic of Korea.
  • 5 Departments of Urology and Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • 6 College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea; Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
  • 7 Soonchunhyang University Bucheon Hospital, Bucheon-si, Gyeonggi-do, 14584, Republic of Korea.
  • 8 Natural Products Research Institute, Seoul National University, Seoul, 08826, Republic of Korea; College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea; Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
  • 9 Natural Products Research Institute, Seoul National University, Seoul, 08826, Republic of Korea; College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea; Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address: ddkim@snu.ac.kr.
  • 10 Natural Products Research Institute, Seoul National University, Seoul, 08826, Republic of Korea; College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea; Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea. Electronic address: hylee135@snu.ac.kr.
PMID: 40614364 DOI: 10.1016/j.redox.2025.103744
Abstract

Chronic obstructive pulmonary disease (COPD) is a major cause of human mortality worldwide and is closely associated with chronic inflammation triggered by environmental toxicants such as lead (Pb) and cadmium (Cd). However, the molecular mechanisms linking Pb/Cd exposure to COPD pathogenesis and effective therapeutic strategies remain poorly defined. In this study, we established a mouse model of environmentally induced COPD by exposing mice to Pb/Cd aerosols using a specialized nebulizer system. Pb/Cd exposure led to characteristic COPD-like pathological features, including alveolar damage, mucus hypersecretion, oxidative stress, and Apoptosis. Transcriptome analysis of lung tissues revealed upregulation of pro-inflammatory cytokines, chemokines, and lipid metabolism-related genes, with macrophages-particularly those expressing MMP-12-identified as key contributors to pulmonary inflammation. Through a targeted stilbenoid compound screen, we identified gaylussacin as a potent suppressor of Pb/Cd-induced MMP-12 expression in macrophages. Mechanistically, gaylussacin suppressed expression of MMP-12 and inflammatory mediators via activation of SIRT1. In a porcine pancreatic Elastase (PPE)-induced emphysema model, oral administration of gaylussacin significantly improved lung function, reduced Apoptosis, ROS production, and inflammation. Pharmacokinetic analysis revealed limited oral bioavailability of gaylussacin but efficient conversion to its active metabolite, pinosylvic acid. Toxicological evaluations confirmed negligible toxicity in normal cells derived from various organs and no significant adverse effects in vivo. Collectively, these findings demonstrate that Pb/Cd inhalation promotes COPD pathogenesis through macrophage-driven inflammation mediated by MMP-12 and that gaylussacin mitigates these effects by enhancing SIRT1 activity. This study supports gaylussacin as a promising therapeutic candidate for the treatment of environmentally induced COPD.

Keywords

Chronic obstructive pulmonary disease; Gaylussacin; Heavy metal; Matrix metalloproteinase-12.

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