ABSTRACT:
The study evaluates the anticataract potential of 3-O-acetyl-11-keto-ß-boswellic acid (AKBA) in a glucose-induced cataractogenesis model using isolated goat lenses. Cataracts, a leading cause of vision impairment, are exacerbated by diabetes through aldose reductase (AR)-mediated polyol pathway disruptions and oxidative stress. Molecular docking studies revealed AKBA’s superior binding affinity (binding energy < -7.0 kcal/mol) to human aldose reductase (HAR), forming stable hydrogen bonds and hydrophobic interactions with active site residues. Molecular dynamics simulations confirmed the stability and specificity of AKBA-HAR complexes, showcasing its potential as a potent AR inhibitor. In vitro investigations demonstrated AKBA’s dose-dependent efficacy in preserving lens transparency and mitigating oxidative damage. Lenses exposed to 55 mM glucose exhibited complete opacity (+++), while those treated with AKBA displayed reduced opacity, comparable to the standard drug, Enalapril. Biochemical assays revealed AKBA's significant impact on oxidative stress markers. Treatment with AKBA increased total protein content (172.33±4.30µg/g) compared to the toxic control (97.9 ± 0.31µg/g). Furthermore, AKBA significantly decreased malondialdehyde (MDA) levels (1.93±0.08µmol/g) and hydrogen peroxide (H2O2) levels (2.73±0.37µmol/g), underscoring its antioxidative efficacy. These results highlight AKBA’s dual mechanism of action: inhibiting AR activity and reducing oxidative stress. This effectively prevents glucose-induced protein aggregation and lipid peroxidation, maintaining lens clarity. Computational and experimental data validate AKBA’s therapeutic potential as an anticataract agent, especially in diabetic contexts. The findings propose AKBA as a promising non-invasive alternative for cataract prevention and management, addressing the limitations of current treatments. Future studies could further explore its pharmacokinetics and in vivo efficacy.