Phytochemical profiling and in silico evaluation of Brassica oleracea stem bioactives as novel aldose reductase inhibitors for diabetic neuropathy treatment
DOI:
https://doi.org/10.69857/joapr.v13i5.1450Keywords:
Brassica oleracea, aldose reductase inhibitor, diabetic neuropathy, molecular docking, ADME analysis, drug-likenessAbstract
Background: Diabetic neuropathy affects over 50% of diabetic patients, causing significant morbidity and economic burden exceeding $327 billion annually. Current treatments offer limited relief, accompanied by considerable side effects. Aldose reductase inhibition represents a promising therapeutic approach, yet synthetic inhibitors face clinical challenges, including hepatotoxicity and inadequate safety margins. This study investigates Brassica oleracea stem bioactives as novel aldose reductase inhibitors. Methodology: Sequential extraction of Brassica oleracea stems employed ethanol and acetone solvents. Phytochemical screening utilized standard chemical tests, while HR-LCMS enabled metabolite identification. Molecular docking against human aldose reductase (PDB: 1US0) was performed using GeinDock Suite. Drug-likeness and ADME properties were assessed using SwissADME, in accordance with Lipinski's Rule of Five. Comprehensive pharmacokinetic parameters were also evaluated. Results and Discussion: HR-LCMS identified 33 bioactive compounds with identification scores >90%. Four lead compounds demonstrated optimal aldose reductase inhibitory potential with superior drug-likeness: Indole-3-acetonitrile (-8.9 kcal/mol, Ki=0.30 μM) approached reference inhibitors epalrestat (-9.9 kcal/mol) and sorbinil (-9.4 kcal/mol) with zero Lipinski violations. 18-Oxooleate (-7.5 kcal/mol) and Salicylamide (-7.6 kcal/mol) exhibited exceptional bioavailability (0.85) with minimal CYP450 inhibition. Phytosphingosine (-6.7 kcal/mol) displayed advantageous peripheral selectivity. Conclusion: Four B. oleracea compounds demonstrate optimal convergence of aldose reductase inhibitory potential and pharmaceutical feasibility, offering promising orally bioavailable candidates for diabetic neuropathy management. Their natural origin and favorable ADME profiles warrant immediate progression to in vitro validation and in vivo studies.
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