涪苓孔酸A减轻年龄诱导的足细胞损伤：网络药理学分析和体外验证

【BACKGROUND/OBJECTIVES】Poria cocos (PC), a well-known medicine-food homologous fungus, has promising reno-protective potential against diabetic kidney disease (DKD); however, its bioactive constituents and underlying molecular mechanisms remain poorly elucidated. This study aimed to decipher the reno-protective potential of PC via network pharmacology, and to subsequently validate the cyto-protective effect of poricoic acid A (PAA), a major active component of PC, against advanced glycation end product (AGE)-induced podocyte injury.

【METHODS】Network pharmacology was adopted to identify active ingredients, core targets and pivotal pathway of PC. Molecular docking was performed to analyze binding interactions between the identified active ingredients and core targets. The AGE-induced podocyte model was used to detect cell viability, mRNA and protein expression.

【RESULTS】Network analysis identified that nine active ingredients, five core targets (PIK3CA, AKT1, TNF, MAPK3, and MAPK8), and pivotal signaling pathways, including the AGE/RAGE signaling pathway, proteoglycans in cancer, etc., constitute key pharmacological nodes of PC's bioactivity. Molecular docking suggested that PAA exhibits favorable binding affinity toward these five key targets. In cellular assays, 100 μg/mL PAA improved cell viability in AGE-induced podocytes. Mechanistically, PAA down-regulated RAGE mRNA expression; suppressed the phosphorylation of PI3K, AKT, and NF-κB; and decreased the levels of NLRP3 inflammasome-related proteins.

【CONCLUSIONS】Collectively, this study first reveals the reno-protective potential of the PC-derived bioactive component PAA in mitigating AGE-induced podocyte injury, which may be associated with the regulation of RAGE-PI3K/AKT and RAGE/NLRP3 signaling axes. These findings provide theoretical evidence at the cellular level for further exploring PC-based functional foods against AGE-induced podocyte injury in DKD.