Grifola frondosa polysaccharide ameliorates adenine-induced CKD by inhibiting TGF-β1/Smad signaling pathway in mice.

BACKGROUND: Chronic kidney disease (CKD) is pathologically characterized by oxidative stress, inflammation, and renal fibrosis, yet effective therapeutic interventions for this condition remains limited. Grifola frondosa polysaccharide (GFP), an active component derived from the edible and medicinal mushroom G. frondosa, has demonstrated antioxidant, anti-inflammatory, and anti-tumor properties. However, its renoprotective effects against CKD and the underlying molecular mechanisms have not been thoroughly elucidated.

RESULTS: Structural analysis revealed that GFP contained pyranose rings with both α- and β-glycosidic linkages. In the adenine-induced CKD mouse model, GFP administration significantly alleviated renal dysfunction and pathological damage, as evidenced by improvements in body weights, kidney index, serum biochemical parameters, and histological findings. Furthermore, GFP administration enhanced renal antioxidant capacities while reducing malondialdehyde contents. GFP also suppressed systemic and renal inflammatory responses, as evidenced by decreased levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Importantly, GFP treatment suppressed renal fibrosis by down-regulation of kidney injury molecule-1 (Kim-1) and transforming growth factor-β1 (TGF-β1) expressions, as well as modulation of the TGF-β1/Smad signaling pathway.

CONCLUSION: Our findings demonstrated that GFP exerted potent renoprotection against adenine-induced CKD in mice, mediated by its antioxidant, anti-inflammatory, and anti-fibrotic activities. The anti-fibrotic mechanism was mediated via the suppression of the TGF-β1/Smad signaling pathway. These results highlighted the potential of GFP as functional food ingredients or adjunctive therapeutic agents for preventing and treating CKD and its complications. © 2026 Society of Chemical Industry.