Codonopsis tangshen extract significantly decreased histological and molecular markers of pulmonary senescence, ameliorated multiple lung function parameters, and attenuated age-related pulmonary fibrosis in aged mice through modulation of FBXW7/TPP1 and HSF1/HSP70 signaling pathways and gut-lung axis involvement.
Key Findings
Results
Codonopsis tangshen (CT) extract significantly decreased histological and molecular markers of pulmonary senescence in naturally aged mice.
C57BL/6J mice were divided into five groups: young control (YCtrl), natural-age control (OCtrl), high-dose CT (H-O-CT, 20.8 g/kg), low-dose CT (L-O-CT, 10.4 g/kg), and positive drug YPF (O-YPF, 20.8 g/kg), with n = 10 per group.
The extract reduced molecular markers associated with cellular senescence in aged lung tissue.
Both high-dose and low-dose CT treatment groups showed reductions in pulmonary senescence markers compared to the natural-age control group.
A bleomycin-induced cellular senescence model in A549 cells was established in vitro to provide complementary evidence supporting these findings.
Results
CT extract attenuated age-related pulmonary fibrosis and ameliorated multiple lung function parameters in aged mice.
Naturally aged mice (OCtrl group) exhibited age-related pulmonary fibrosis that was reduced following CT extract treatment.
Multiple lung function parameters were improved in CT-treated aged mice compared to untreated aged controls.
Both high-dose (20.8 g/kg) and low-dose (10.4 g/kg) CT groups were evaluated for effects on fibrosis and lung function.
Results were described as significant attenuation of age-related pulmonary fibrosis.
Results
The protective effects of CT extract on pulmonary senescence and fibrosis were associated with modulation of the FBXW7/TPP1 and HSF1/HSP70 signaling pathways.
Transcriptomic analysis was used to identify relevant signaling pathways altered by CT treatment.
Protein validation confirmed changes in the FBXW7/TPP1 signaling pathway.
The HSF1/HSP70 signaling pathway was also identified as a mechanism underlying CT's protective effects.
These pathway modulations were described as associated with the extract's anti-senescence and anti-fibrotic effects in aged lung tissue.
Results
CT extract reshaped gut microbiota composition and enhanced expression of intestinal barrier markers, supporting involvement of the gut-lung axis.
Gut microbiota composition was analyzed in CT-treated versus untreated aged mice.
CT treatment enhanced expression of intestinal MUC2, a key mucus barrier protein.
Expression of tight-junction proteins in the intestinal barrier was also enhanced following CT treatment.
These findings support possible involvement of the gut-lung axis in CT's protective effects against pulmonary fibrosis.
The reshaping of gut microbiota composition was identified as a component of CT's mechanism of action.
Methods
A bleomycin-induced cellular senescence model in A549 cells was used in vitro to provide complementary mechanistic evidence for CT's anti-senescence effects.
A549 cells (human alveolar epithelial cells) were treated with bleomycin to induce cellular senescence.
This in vitro model served to complement the in vivo findings from the naturally aged mouse model.
The cell model provided additional evidence for CT extract's effects on pulmonary cellular senescence.
Bleomycin-induced senescence is an established model for studying lung cell senescence relevant to fibrosis.
Conclusions
Codonopsis tangshen Oliv. is identified as a promising preclinical treatment candidate for aging and age-related fibrotic lung injury.
CT is described as a widely used medicinal and edible homologous plant in traditional Chinese medicine.
Prior to this study, its pharmacological effects on natural aging and age-related pulmonary fibrosis were 'still not fully elucidated.'
The study authors describe the results as highlighting 'the potential of Codonopsis tangshen Oliv. as a promising preclinical treatment for the intervention and management of aging and age-related fibrotic lung injury.'
The study used a positive drug control group (O-YPF, 20.8 g/kg) for comparison with CT treatment groups.
What This Means
This research suggests that an extract from Codonopsis tangshen, a plant used in traditional Chinese medicine, may help protect aging lungs from fibrosis — a condition where lung tissue becomes scarred and stiff, making breathing progressively harder. Scientists tested the extract in naturally aged mice by giving them either a high or low dose of the extract over a period of time. They found that treated mice showed less lung scarring, reduced signs of cellular aging (called senescence) in lung tissue, and better lung function compared to untreated aged mice. The researchers also tested the extract on lung cells in the laboratory, using a chemical called bleomycin to mimic the cellular aging process, and found consistent protective effects.
The study identified two specific biological pathways — FBXW7/TPP1 and HSF1/HSP70 — that appear to be involved in how the extract protects the lungs. Additionally, CT extract appeared to benefit the gut microbiome (the community of bacteria living in the intestines) and strengthened the gut's protective barrier by increasing levels of a mucus protein called MUC2 and proteins that hold intestinal cells tightly together. This suggests the extract may work in part through the 'gut-lung axis,' a concept that the health of the gut can influence the health of the lungs.
This research suggests that Codonopsis tangshen extract could be a candidate for further development as a treatment to slow or manage age-related lung disease, though it is important to note these are preclinical findings in mice and cells, and more research including human clinical trials would be needed before any medical applications could be established.
Zhao Y, Gong Y, Zhu H, Zhang W, Cai M, Yang C, et al.. (2026). Codonopsis tangshen Attenuates Age-Related Pulmonary Fibrosis Through Senescence and Gut-Lung Axis Modulation.. Nutrients. https://doi.org/10.3390/nu18193289