Xiaoqinglong decoction improves chronic obstructive pulmonary disease by modulating PI3K/AKT-NRF2/NF-κB-mediated...

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disorder with limited therapeutic options. We aimed to investigate whether Xiaoqinglong decoction (XQLD) alleviates COPD by modulating senescence-associated phenotypes via the PI3K/AKT-NRF2/NF-κB pathway.

COPD rat models were established by cigarette smoke exposure, lipopolysaccharide (LPS) administration, and cold stimulation, followed by gavage of XQLD (2 mL/day) for 14 days. In vitro COPD models were induced in A549 cells using LPS plus cigarette smoke extract, then treated with 1 mg/mL XQLD for 28h, with or without PI3K overexpression. XQLD compositions were analyzed. In vivo, pulmonary function, bronchoalveolar lavage fluid (BALF) cell counts, histopathology, collagen deposition, and apoptosis were assessed. In vitro, cell apoptosis and viability were assessed. Both animal and cell experiments detected senescence-associated secretory phenotype (SASP) markers and PI3K/AKT-NRF-2/NF-κB pathway-related protein expression.

XQLD's main components were alkaloids, monoterpene glycosides, flavonoid glycosides, triterpene saponins, amino acids, and organic acids. XQLD improved pulmonary function, reduced macrophage, neutrophil, and lymphocyte numbers in BALF, and relieved lung histopathological damage, collagen deposition, and apoptosis in COPD rats. In vitro, XQLD promoted viability but inhibited apoptosis in COPD cells. Animal and cell experiments showed that XQLD decreased SASP markers (TNF-α/IL-1β/IL-8/IL-6/P16/P21/P53/MMP-9/MMP-12), PI3K/AKT/NF-κB p65/IκB phosphorylation, and Keap1 expression, but increased NRF-2, HO-1, and NQO-1 levels. However, these effects of XQLD on COPD were abrogated by PI3K overexpression.

XQLD attenuates senescence-associated phenotypes in COPD by modulating the PI3K/AKT-NRF2/NF-κB pathway, providing a novel mechanistic insight and highlighting this pathway as a potential therapeutic target for COPD.