Sagittaria sagittifolia polysaccharide extract attenuates inflammation and senescence through dual involvement of TLR4/NF-κB and SIRT1/NF-κB in vivo and in vitro models of COPD.

Sagittaria sagittifolia polysaccharide (SSP) extract, a key bioactive component of the natural herb Sagittaria sagittifolia, possesses multiple biological activities, including anti-inflammatory and antioxidant effects, demonstrating potential in the prevention and treatment of chronic obstructive pulmonary disease (COPD). This study aims to investigate the efficacy of SSP extract in COPD and explore whether its anti-inflammatory and anti-aging effects involve the regulation of NF-κB. A COPD mouse model and BEAS-2B cell injury model were established using lipopolysaccharide (LPS) combined with cigarette smoke (CS). RNA sequencing was employed to identify potential targets of SSP extract. SSP extract significantly reduced the expression levels of NF-κB, pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and the number of Ly6g-labeled neutrophils in COPD mice. SSP extract also inhibited the expression levels of COX-2 and CXCL1 in BEAS-2B cells. TLR4 and SIRT1 are important upstream regulatory proteins of NF-κB. This study showed that SSP extract effectively suppressed the expression of TLR4, MyD88, IRAK1, TRAF6, increased SIRT1 protein expression, and inhibited senescence markers (p53, p21, p16, and RB) in COPD mice. In BEAS-2B cells, SSP extract decreased acetylated NF-κB levels, reduced the number of β-gal-positive cells, and alleviated G1 phase cell cycle arrest, thereby partially inhibiting senescence. These findings suggest that SSP extract holds potential for prevention and treatment of COPD. Its effects are associated with changes in the TLR4/NF-κB and SIRT1/NF-κB pathways, as well as reduced inflammation and senescence.