Total flavonoids of litchi seed (TFL) suppresses p65, reducing SASP and ameliorating pulmonary fibrosis

Cellular senescence, a state of irreversible cell cycle arrest, is a major contributor to aging and age-related diseases like pulmonary fibrosis. Senescent cells secrete a pro-inflammatory mix of factors known as the Senescence-Associated Secretory Phenotype (SASP), which perpetuates inflammation and tissue damage. Current treatments for pulmonary fibrosis often have limited efficacy or significant side effects, highlighting an urgent need for safe and effective natural interventions. Flavonoids, abundant in plants, are increasingly recognized for their anti-aging and anti-inflammatory properties, making them promising candidates to target the SASP pathway and mitigate senescence-driven pathologies.

Researchers investigated the anti-senescence and anti-fibrotic effects of Total flavonoids of litchi seed (TFL) using both in vitro cellular models and an in vivo mouse model of pulmonary fibrosis. In vitro, TFL was applied to cells to assess its impact on replicative senescence and stress-induced senescence, as well as its ability to alleviate the SASP and reduce DNA damage caused by bleomycin (BLM). In mice, pulmonary fibrosis was induced by BLM, and the effects of TFL treatment on lung senescence, fibrosis markers like p21 protein levels, and overall pathology were evaluated. Transcriptome profiling was performed to elucidate TFL's anti-aging mechanisms, and gut microbiome analysis was conducted to examine changes in microbial composition and function.

Total flavonoids of litchi seed (TFL) effectively delayed both replicative and stress-induced cellular senescence. TFL significantly alleviated the SASP and reduced the degree of DNA damage induced by bleomycin (BLM) in cellular models. In vivo, TFL counteracted stress-induced pulmonary senescence and fibrosis in mice, notably reducing the protein level of p21 in mouse lung tissue. Transcriptome profiling revealed that TFL's anti-aging mechanism primarily involves inhibiting the SASP. Mechanistically, TFL was found to suppress p65 protein expression, which in turn inhibited the production of pro-inflammatory cytokines IL-1α and IL-1β, thereby delaying cellular senescence. Gut microbiome analysis further demonstrated that BLM exposure altered the abundance and functions of the mouse gut microbiome, and TFL treatment successfully reversed these detrimental changes. This multi-faceted action underscores TFL's potential.

TFL suppresses p65 protein expression, inhibiting IL-1α and IL-1β to delay cellular senescence and ameliorate pulmonary fibrosis.