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

in International journal of biological macromolecules by Man-Yu Zhou, Bing-Qing Liu, Xin Gao, Shu-Jing Zhang, Yang Jiang, Tao Yang, Jian-Bin Sun, Xi Zhang, Yan Liao

TLDR

  • The study found that Sagittaria sagittifolia polysaccharide (SSP) extract showed therapeutic potential in age-related cataract (ARC) by regulating Nrf2/ERS-mediated apoptosis, providing a potential treatment option for ARC.

Abstract

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 (HO)-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 Caand 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.

Overview

  • This study explored the therapeutic potential of Sagittaria sagittifolia polysaccharide (SSP) extract in age-related cataract (ARC) and investigated its underlying mechanisms.
  • SSP exhibits anti-oxidant and anti-apoptotic effects, making it a potential treatment for ARC.
  • The study used sodium selenite-induced cataracts in rats and hydrogen peroxide-induced human lens epithelial B3 (HLEB3) cells to evaluate the effects of SSP on ARC.

Comparative Analysis & Findings

  • SSP significantly improved lens opacity and pathological changes, and alleviated apoptosis and endoplasmic reticulum stress (ERS)-related injury indicators in both rat and human cell models.
  • SSP inhibited intracellular Caand protein expression of pro-apoptotic proteins and increased the expression of anti-apoptotic proteins.
  • After Nrf2 knockdown technology was applied in HLEB3 cells, SSP still demonstrated its protective role by activating Nrf2 and inhibiting ERS-mediated apoptosis.

Implications and Future Directions

  • The study provides potential evidence for the use of SSP in preventing or delaying ARC.
  • Future studies should investigate the optimal dosage and administration route of SSP for therapeutic application.
  • The role of Nrf2 in SSP-mediated protection against ARC should be further explored, as it appears to play a critical role in the therapeutic effects of SSP.
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