Exploring the Mechanisms Underlying the Effects of Cortex Moutan and Its Active Ingredients on Kidney Injury Through Network Pharmacology and Experimental Validation

INTRODUCTION: Cortex Moutan (CM), the root bark of Paeonia suffruticosa, is a valuable herb. This study systematically explored the mechanisms of CM, providing an experimental basis for the use of its active ingredient quercetin as an important compound to treat kidney injury (KI). METHODS: Network pharmacology and molecular docking were employed to identify the active ingredients, key molecules, and signaling pathways of CM in the treatment of KI. Cellular and molecular biology assays validated its anti-KI effects and underlying mechanisms. Additionally, reports of cisplatin-related AE were analyzed via the FDA AE reporting system. RESULTS: Quercetin, (+)-catechin, and kaempferol were identified as major active ingredients of CM, with AKT1, TNF-α, IL-1β, and BCL-2 as key molecules. GO analysis revealed the involvement of cytokine activity and receptor ligand activation, whereas KEGG analysis revealed the involvement of the TNF signaling pathway. Molecular docking confirmed the stable binding between quercetin and AKT1. In cisplatin-induced mouse and NRK-52E cell-KI models, quercetin reversed cisplatin cytotoxicity by reducing ROS levels, downregulating Tnf-α and Bax/Bcl-2 expressions, and inhibiting AKT1, p-p65, p-IκB, and BAX/BCL-2. DISCUSSION: Previous studies have shown that CM exerts kidney-protective effects by regulating NO/cytokine levels, inhibiting NF-κB activation, and reducing ROS levels. As a vital component of CM, quercetin mediates multitarget renoprotection, as validated in animal KI models, but its development is limited by insufficient clinical data and low bioavailability. CONCLUSION: This study revealed the critical role of quercetin in the effects of CM against KI, with its relevant signaling pathway potentially correlated with TNF-α/AKT1/NF-κB.