Anthrahydroquinone-2,6-Disulfonate Restores Lung Function in COPD Through Keap1/Nrf2 Pathway Activation

Area of Science:

• Pulmonary Medicine
• Oxidative Stress Research
• Pharmacology

Background:

• Chronic obstructive pulmonary disease (COPD) is a leading global cause of mortality, significantly driven by oxidative damage.
• Current therapeutic strategies for COPD struggle to effectively mitigate oxidative stress and restore lung function.
• Anthrahydroquinone-2,6-disulfonate (AH2QDS) exhibits potent antioxidant properties, but its efficacy in COPD remains under investigation.

Purpose of the Study:

• To investigate the therapeutic potential of AH2QDS in COPD models.
• To elucidate the underlying mechanisms of AH2QDS action, focusing on the Keap1-Nrf2 pathway.
• To evaluate the impact of AH2QDS on lung function, oxidative stress, inflammation, and apoptosis in COPD.

Main Methods:

• Established in vivo and in vitro COPD models using lipopolysaccharide (LPS) and cigarette smoke/extract (CS/CSE).
• Assessed lung function parameters, histopathology, oxidative stress markers, inflammatory cytokines, and apoptosis.
• Utilized molecular docking to predict AH2QDS interaction with Keap1-Nrf2 proteins, confirmed by immunoblotting.

Main Results:

• AH2QDS treatment significantly improved lung function and mitigated lung tissue injury in COPD model rats.
• Reduced levels of reactive oxygen species (ROS), inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-33), and apoptosis were observed.
• AH2QDS upregulated antioxidant enzymes (SOD, CAT, GSH-PX) and the Keap1-Nrf2 pathway, including Nrf2, HO-1, and NQO1 expression.

Conclusions:

• AH2QDS effectively counteracts oxidative damage and reduces inflammation in COPD.
• Activation of the Keap1-Nrf2 pathway by AH2QDS is a key mechanism for its therapeutic effects.
• AH2QDS demonstrates significant potential for normalizing lung function in COPD patients.