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

OBJECTIVE: 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. Both animal and cell experiments detected senescence-associated secretory phenotype (SASP) markers and PI3K/AKT-NRF-2/NF-κB pathway-related protein expression. 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. CONCLUSIONS: 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.