Network pharmacology-based strategy to investigate pharmacological mechanisms of polysaccharide-free Lycium barbarum extract for chronic kidney disease treatment and verification in an animal model.

Abstract

Lycium barbarum polysaccharides (LBP) have shown renal protection effects. However, research on other active components of L. barbarum extract (ELB) for the therapy of chronic kidney disease (CKD) is limited. This study aims to investigate the renoprotective effects and molecular mechanisms of ELB in CKD. ELB was extracted from L. barbarum fruits using 85% ethanol reflux, followed by vacuum concentration and sequential extraction to remove polysaccharides. Chemical components and target genes were identified using TCMSP and UniProt databases, followed by pharmacology network construction and GO/KEGG pathway analysis. A 5/6 nephrectomy model in Sprague-Dawley rats was used to study the renoprotective effects of ELB, with H&E staining and biochemical analyses. Western blot analysis assessed IL-6 and VEGF expression in renal tissues. Chemical analysis of ELB identified 188 components, with 45 meeting screening criteria, and 34 linked to 94 target genes. The intersection with CKD-related genes yielded 39 overlapping genes, with quercetin having the most targets. GO/KEGG pathway analyses highlighted significant biological processes and pathways. A PPI network identified IL-6, VEGFA, CASP3, EGFR, ESR1, and PPARG as hub genes. In a 5/6 nephrectomy rat model, ELB treatment significantly reduced renal damage, serum BUN and SCr levels, as well as IL-6 and VEGF expression in renal tissues, validating its renoprotective effects and supporting bioinformatics predictions. This work identified the intricate components and pharmacological actions of ELB, which is devoid of LBP. The findings preliminarily confirm the potential of ELB as a novel therapeutic agent for preventing and managing CKD.