Uncovering the mechanistic basis of Rheum palmatum L. (rhubarb) in the treatment of chronic kidney disease: an integrative approach using network pharmacology, molecular docking, and experimental validation

Rheum palmatum L. (Rhubarb) has shown potential in managing Chronic Kidney Disease (CKD) but its protective mechanisms remain unclear. This study investigates rhubarb’s therapeutic effects and underlying mechanisms in CKD. High-performance liquid chromatography (HPLC) established a rhubarb fingerprint to ensure quality control. Network pharmacology and Mendelian randomization identified primary CKD therapeutic targets. Inflammation, oxidative stress, and renal performance were assessed through ELISAs and biochemical tests. Renal structure and fibrosis were examined using hematoxylin-eosin and Masson staining. Protein expression related to fibrosis, apoptosis, and NF-κB pathway activity was measured via Western blotting. Discovery Studio 2019 (DS 2019) was used for molecular docking. HPLC fingerprinting confirmed high batch-to-batch consistency of rhubarb, identifying five key anthraquinones (aloe-emodin, rhein, emodin, chrysophanol, physcion) with similarity indices >0.91. Network pharmacology identified 19 active compounds targeting 2,597 CKD-related proteins, with 47 overlapping targets including IL6, TNF, TP53, CASP3, and IL1B as core nodes. MR analysis demonstrated a statistically significant causal association between TNF and CKD (OR = 1.02, p p p p p p p Rhubarb significantly reduces renal impairment, fibrosis, inflammation, and apoptosis through the NF-κB pathway, supporting its traditional use and potential as an adjunct therapy for CKD.