Syringin reduces cellular senescence and pulmonary fibrosis in mice and cell models
Computational screening identified the natural compound, which interacts with CHK1 to blunt replication stress and fibrotic signaling.
Chinese journal of natural medicines · 1 Oct · Wang Y, Yin G, Niu M et al.
In human lung datasets, cultured fibroblasts, and mice with bleomycin-induced lung injury, researchers investigated how targeting senescence could treat idiopathic pulmonary fibrosis. The team analyzed bulk and single-cell RNA sequencing data to map senescence programs, identifying senescent fibroblasts as key drivers expressing senescence-associated secretory phenotype factors. Using compound prioritization algorithms, they identified syringin, a plant-derived phenylpropanoid glycoside. In TGFβ1-stimulated fibroblasts and bleomycin-treated mice, syringin attenuated fibroblast activation, reduced senescence markers, and relieved pulmonary fibrosis. Mechanistically, syringin counteracted replication stress-associated signaling. Molecular assays and docking indicated that syringin interacts with CHK1, and knocking down CHK1 partially blocked syringin's effects on the ATR/CHK1-p53 pathway.
Why it matters
Idiopathic pulmonary fibrosis closely tracks chronological aging and involves senescent cell accumulation. Targeting senescence-associated replication stress pathways may offer a viable therapeutic approach for age-related fibrotic lung disorders.
Caveats
The in vivo therapeutic findings rely on a chemically induced mouse model, which does not fully capture chronic human disease. Clinical studies are necessary to evaluate the safety and efficacy of syringin in human patients.
The paper
Targeting senescence-associated fibrotic signatures identifies syringin as an effective modulator of the ATR/CHK1-p53 axis in idiopathic pulmonary fibrosis
Wang Y, Yin G, Niu M et al.
Chinese journal of natural medicines
doi.org/10.1016/s1875-5364(26)61215-0