Structural characterization of Plantago asiatica L. polysaccharide and its therapeutic potential against calcium oxalate kidney stones

Kidney stone disease is a common pathological mineralization disorder with high recurrence. Plantago asiatica L. has traditionally been used for urinary calculi, but its active constituents and mechanisms remain unclear. Here, a water-soluble polysaccharide from P. asiatica L. (PLP) was isolated, structurally characterized, and evaluated for anti-nephrolithic activity. PLP possessed a glucan-rich backbone mainly composed of →4)-α-D-Glcp-(1→ and →4,6)-α-D-Glcp-(1→ residues, with O-6-linked terminal α-D-Glcp branches and minor β-1,3/1,4-glucan and arabinogalactan moieties. PLP inhibited calcium oxalate (CaOx) nucleation, growth, and aggregation and promoted the transformation of pathogenic CaOx monohydrate into less-adhesive CaOx dihydrate. In renal tubular epithelial cells, PLP reduced reactive oxygen species, preserved mitochondrial membrane potential and lysosomal integrity, and inhibited apoptosis and crystal-adhesion molecule expression. In stone-bearing mice, PLP reduced renal crystal deposition, tubular injury, inflammatory infiltration, and improving renal function. Integrated transcriptomic and untargeted metabolomic analyses showed that PLP suppressed injury- and inflammation-related genes, restored tubular transport, and regulated peroxisomal function, purine and glyoxylate/dicarboxylate metabolism, and the TCA cycle. Collectively, PLP protects against CaOx nephrolithiasis by coordinating crystal modulation with restoration of renal redox and metabolic homeostasis, thereby providing mechanistic support for its development as a natural anti-urolithic candidate.