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 < 0.05), with positive trends for IL6 and CASP3. In CKD rat models, rhubarb significantly improved renal function by reducing blood urea nitrogen (BUN), serum creatinine (SCr), and uric acid (UA) levels (p < 0.05). Histopathology showed reduced glomerulosclerosis, tubular atrophy, interstitial fibrosis, and inflammatory infiltration after treatment. Rhubarb markedly decreased renal fibrosis markers including collagen I, collagen III, α-SMA, and TGF-β (p < 0.01). Pro-inflammatory cytokines IL-6, IL-1β, and TNF-α levels were significantly suppressed (p < 0.001). Antioxidant enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were restored, while lipid peroxidation (LPO) was reduced (p < 0.05). Rhubarb inhibited NF-κB pathway activation by lowering phosphorylated NF-κB and IκBα, and increasing total IκBα expression (p < 0.01). Apoptosis-related proteins showed upregulated Bcl-2 and downregulated Bax and cleaved caspase-3 expression (p < 0.05). Molecular docking confirmed strong binding affinities of rhubarb's core compounds with key targets such as TNF and IL6, supporting their therapeutic roles. 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.

Vascular calcification (VC) is a critical pathological condition associated with significant morbidity and mortality. This study employs a hybrid approach of network pharmacology and molecular biology to delineate the therapeutic mechanisms of salidroside (SAL), an active compound from Rhodiola crenulata, against VC. Through database mining and network analysis, 388 SAL targets intersecting with 2871 VC-associated targets were identified, resulting in 208 common targets. A protein-protein interaction (PPI) network constructed via the String database and topological analysis in Cytoscape 3.9.1 pinpointed 10 key targets, including IL6, TNF, TP53, IL1B, HIF1A, CASP3, and STAT3, among others. The identified genes were concentrated in the lipid and atherosclerosis pathways, indicating that the improvement of VC by SAL may occur through the regulation of abnormal expression of lipid and inflammatory factors. It was also found that SAL inhibits the abnormal expression of inflammatory factors, thereby activating the JAK2/STAT3 pathway to intervene in the progression of VC. The JAK2/STAT3 pathway is a key molecular mechanism by which SAL prevents further deterioration of VC. Functional enrichment analyses revealed the involvement of these targets in inflammatory responses and lipid metabolism, pivotal pathways in VC. In vivo studies in rats demonstrated SAL's efficacy in mitigating dyslipidemia and vascular inflammation, with improved serum lipid profiles and reduced vascular calcium deposition. The mechanistic exploration, grounded in Western blot analysis, demonstrated salidroside's ability to regulate the JAK2/STAT3 signaling pathway, highlighting its potential as a modulator in this critical molecular mechanism and offering a potential therapeutic target for VC. The strength of this research lies in its methodological rigor, integrating computational predictions with in vivo validations. This comprehensive approach establishes a robust framework for exploring the therapeutic mechanisms of natural compounds in combating VC.

Vascular calcification (VC) is a critical pathological condition associated with significant morbidity and mortality. This study employs a hybrid approach of network pharmacology and molecular biology to delineate the therapeutic mechanisms of salidroside (SAL), an active compound from Rhodiola crenulata, against VC. Through database mining and network analysis, 388 SAL targets intersecting with 2871 VC-associated targets were identified, resulting in 208 common targets. A protein-protein interaction (PPI) network constructed via the String database and topological analysis in Cytoscape 3.9.1 pinpointed 10 key targets, including IL6, TNF, TP53, IL1B, HIF1A, CASP3, and STAT3, among others. The identified genes were concentrated in the lipid and atherosclerosis pathways, indicating that the improvement of VC by SAL may occur through the regulation of abnormal expression of lipid and inflammatory factors. It was also found that SAL inhibits the abnormal expression of inflammatory factors, thereby activating the JAK2/STAT3 pathway to intervene in the progression of VC. The JAK2/STAT3 pathway is a key molecular mechanism by which SAL prevents further deterioration of VC. Functional enrichment analyses revealed the involvement of these targets in inflammatory responses and lipid metabolism, pivotal pathways in VC. In vivo studies in rats demonstrated SAL's efficacy in mitigating dyslipidemia and vascular inflammation, with improved serum lipid profiles and reduced vascular calcium deposition. The mechanistic exploration, grounded in Western blot analysis, demonstrated salidroside's ability to regulate the JAK2/STAT3 signaling pathway, highlighting its potential as a modulator in this critical molecular mechanism and offering a potential therapeutic target for VC. The strength of this research lies in its methodological rigor, integrating computational predictions with in vivo validations. This comprehensive approach establishes a robust framework for exploring the therapeutic mechanisms of natural compounds in combating VC.