Mechanistic insights into baicalein's anti-inflammatory effects in COPD: Targeting oxidative stress and CD8⁺ T cell...

Chronic obstructive pulmonary disease (COPD) is ​​defined by chronic airway inflammation. Traditional Chinese herb Pinellia ternata is used to treat COPD, but its bioactive components and mechanisms are unclear.

To identify the key active component of Pinellia ternate and explore its therapeutic mechanisms in COPD.

The principal active components and their associated targets of Pinellia ternata were identified through network pharmacology analysis. Using the BEAS-2B cell, the effects of baicalein on oxidative stress, apoptosis, and inflammation induced by cigarette smoke extract (CSE) were evaluated. A COPD mouse model was established to assess the protective effects of baicalein on airway inflammation, mucus secretion, and lung tissue damage. Flow cytometry was used to analyze the proportion of immune cells in lung tissues. UPLC-Q/TOF-MS was employed to evaluate the metabolic profile changes in bronchoalveolar lavage fluid (BALF).

Pinellia ternata interacted with 70 COPD-related targets, with hypoxia-inducible factor 1-alpha (HIF1A) as a key target. Baicalein, one of the major components of Pinellia ternata, alleviates oxidative stress, apoptosis, and inflammation in CSE-treated BEAS-2B cells by inhibiting HIF1A. In COPD mice, baicalein alleviated airway inflammation and lung damage and decreased HIF1A expression. Baicalein modulated the CD4⁺/CD8⁺ T cell ratio in lung tissues, reducing the cytotoxicity of CD8⁺ T cells, and altered metabolic pathways in BALF.

Baicalein exerts anti-inflammatory effects in COPD by inhibiting HIF1A-mediated oxidative stress and apoptosis in bronchial epithelial cells and modulating CD8⁺ T cell cytotoxicity. This study provides a basis for developing baicalein as a potential COPD therapy.