Sagittaria sagittifolia polysaccharide extract regulates Nrf2 to improve endoplasmic reticulum stress-mediated apoptosis in rat cataracts and HLEB3 cells.

Age-related cataract (ARC) remains the leading cause of blindness worldwide. Sagittaria sagittifolia polysaccharide (SSP) extract, a key component of Sagittaria sagittifolia L., exhibits anti-oxidant and anti-apoptotic effects with potential applications in ARC. This study aimed to explore the therapeutic potential of SSP in ARC and the underlying mechanisms. In sodium selenite-induced cataracts in rats and hydrogen peroxide (H2O2)-induced human lens epithelial B3 (HLEB3) cells, SSP significantly improved lens opacity and pathological changes and alleviated apoptosis and endoplasmic reticulum stress (ERS)-related injury indicators (by inhibiting the intracellular Ca2+ and protein expression of Bcl-2-associated X, cleaved caspase-3, binding immunoglobulin heavy chain protein, protein kinase RNA-like kinase, inositol-requiring enzyme 1α, activating transcription factor 6, C/EBP homology protein, c-Jun N terminal kinase, caspase-12, and calpain-2). In addition, SSP increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1, sarco/endoplasmic reticulum-type calcium transport ATPase 2, and B-cell lymphoma-2. After applying Nrf2 knockdown technology by transferring short interfering RNA in HLEB3 cells, SSP demonstrated its protective role by activating Nrf2 and inhibiting ERS-mediated apoptosis. These findings indicate that SSP may protect against ARC by regulating Nrf2/ERS-mediated apoptosis, providing potential evidence for its use in preventing or delaying ARC.