Mechanistic Insights Into Astragali Radix n‐Butanol on Podocyte Injury via Cell Cycle Regulation

The traditional Chinese medicine Astragali Radix (AR) shows therapeutic effects on nephrotic syndrome (NS), with AR n‐butanol (AR‐B) particularly ameliorating podocyte injury. Nevertheless, the molecular mechanisms are unclear. This study investigates how serum containing AR‐B (AR‐B‐S) mitigates podocyte injury. Using rats as serum donors, we established an adriamycin (ADR)‐induced injury model. The findings indicated that the optimal preparation protocol for AR‐B‐S was as follows: using serum collected 3.5 h after administration, incubating it at 56°C for 30 min, and employing a final concentration of 2.5%. Subsequently, compositional analysis using UPLC‐MS technology and integrated network pharmacology predicted potential pathways, with more than 30% of AR‐B‐S targets for amelioration of podocyte injury related to the cell cycle. Furthermore, ADR was shown to facilitate the transition of MPC5 cells from a quiescent to a differentiated state. Additionally, ADR was demonstrated to have the ability to cause mitotic arrest in podocytes, which in turn leads to apoptosis. Conversely, intervention with AR‐B‐S was found to reverse ADR‐induced mitotic arrest through the PI3K/Akt pathway, reducing podocyte apoptosis. This study showed AR‐B‐S reduces podocyte damage by regulating the cell cycle, providing a methodological reference for herbal serum preparation and suggesting a new therapeutic target for kidney disease.