Calycosin extracted from Astragali Radix reduces NETs formation to improve renal fibrosis via TLR4/NF-κB pathway.

Ethnopharmacological Relevance: Astragali Radix (A. Radix) is the dry root of the leguminous plants Astragalus membranaceus (Fisch) Beg. var. mongholicus (Beg) Hsiao, and Astragalus membranaceus (Fisch) Bge., being used as a medicinal and edible resource. AR is used in traditional Chinese medicine prescriptions to treat chronic nephritis. Calycosin (CA), the primary active compound derived from Astragali Radix, shows significant antifibrotic effects in multiple organs, but the anti-renal fibrosis effect of CA is rarely reported, and the associated mechanism of action is still need to be elucidated.

Aim Of The Study: The objective of this study was to investigate the protective effects of CA on the kidney against renal fibrosis and the underlying molecular mechanisms. Evaluation of the effects of CA on renal fibrosis using unilateral ureteral obstruction (UUO) mice and transforming growth factor β1 (TGF β1)-induced cell fibrosis. The mechanism of action supporting the investigated anti-renal fibrosis effects were studied by a series of biochemical experiments.

Results: Our research demonstrated that CA reduced kidney cell fibrosis in mice with UUO and in TGF-β1-stimulated NRK-52E cells. Additionally, CA mitigated renal fibrosis via toll-like receptor 4 (TLR4)/ nuclear factor-kappa B (NF-κB) and had a synergistic effect with resatorvid (TAK-242). Our findings reveal an unobserved impact of CA in inhibiting neutrophil extracellular traps (NETs) formation in UUO mice and neutrophils activated by phorbol 12-myristate 13-acetate.

Conclusions: Our findings revealed that calycosin reduces NETs production to alleviate renal fibrosis via TLR4 and NF-κB, supporting its potential as a strategy for treating renal fibrosis.