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<p>This study investigates the neuroprotective potential of Chromium-D-Phenylalanine [Cr(D-Phe)₃] using molecular docking, molecular dynamics (MD) simulations and an in vivo rotenone-induced Parkinsonism model in rats. Molecular docking revealed a strong binding affinity between Cr(D-Phe)₃ and α-synuclein (PDB ID: 1XQ8), with a docking score of -8.9&#xa0;kcal/mol, surpassing Levodopa (-7.7&#xa0;kcal/mol). MD simulations further confirmed the stability of the Cr(D-Phe)₃-α-synuclein complex, demonstrating minimal RMSD fluctuations and sustained structural compactness over a 100-ns simulation period. In in vivo study&#xa0;in rats, Cr(D-Phe)₃ was administered orally at doses of 20, 40 and 80&#xa0;µg/kg. The 40&#xa0;µg/kg dose exhibited the most pronounced neuroprotective effects. Behavioural assessments showed significant improvement, with a 13.4% (p &lt; 0.05) reduction in catalepsy duration, a 173.7% (p &lt; 0.01) increase in locomotor activity and a 207.6% (p &lt; 0.01) enhancement in neuromuscular coordination compared to the rotenone-treated group. Biochemical analyses demonstrated substantial restoration of antioxidant defences, with catalase levels increasing by 14.3% (p &lt; 0.05) and GSH levels by 104.6% (p &lt; 0.01). Oxidative and nitrative stress markers were significantly reduced, with lipid peroxidation decreasing by 22.7% (p &lt; 0.001) and nitrite levels by 26.3% (p &lt; 0.001). Furthermore, Cr(D-Phe)₃ effectively suppressed neuroinflammation, lowering TNF-α levels by 35.5% (p &lt; 0.001), while dopamine levels were restored by 45.4% (p &lt; 0.001) compared to rotenone-treated rats. Histopathological analysis confirmed the preservation of neuronal integrity in the substantia nigra and cortical regions. These findings suggest that Cr(D-Phe)₃ mitigates Parkinsonism-associated neurodegeneration by reducing oxidative stress, suppressing neuroinflammation and preserving dopaminergic neuronal function. Cr(D-Phe)₃ holds promise as a potential therapeutic candidate for Parkinsonism, warranting further investigation.</p>

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Neuroprotective Potential of Chromium-D-Phenylalanine: Insights from Molecular Docking, Dynamics and Rotenone-Induced Parkinsonism in Rats

  • 期刊论文

  • 发表日期：

    2025年5月29日

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  • K. N. Anitha,
  • Mohammed Mutahir,
  • Shivsharan B. Dhadde,
  • B. S. Gowrishankar,
  • Vivek Chandramohan

摘要

This study investigates the neuroprotective potential of Chromium-D-Phenylalanine [Cr(D-Phe)₃] using molecular docking, molecular dynamics (MD) simulations and an in vivo rotenone-induced Parkinsonism model in rats. Molecular docking revealed a strong binding affinity between Cr(D-Phe)₃ and α-synuclein (PDB ID: 1XQ8), with a docking score of -8.9 kcal/mol, surpassing Levodopa (-7.7 kcal/mol). MD simulations further confirmed the stability of the Cr(D-Phe)₃-α-synuclein complex, demonstrating minimal RMSD fluctuations and sustained structural compactness over a 100-ns simulation period. In in vivo study in rats, Cr(D-Phe)₃ was administered orally at doses of 20, 40 and 80 µg/kg. The 40 µg/kg dose exhibited the most pronounced neuroprotective effects. Behavioural assessments showed significant improvement, with a 13.4% (p < 0.05) reduction in catalepsy duration, a 173.7% (p < 0.01) increase in locomotor activity and a 207.6% (p < 0.01) enhancement in neuromuscular coordination compared to the rotenone-treated group. Biochemical analyses demonstrated substantial restoration of antioxidant defences, with catalase levels increasing by 14.3% (p < 0.05) and GSH levels by 104.6% (p < 0.01). Oxidative and nitrative stress markers were significantly reduced, with lipid peroxidation decreasing by 22.7% (p < 0.001) and nitrite levels by 26.3% (p < 0.001). Furthermore, Cr(D-Phe)₃ effectively suppressed neuroinflammation, lowering TNF-α levels by 35.5% (p < 0.001), while dopamine levels were restored by 45.4% (p < 0.001) compared to rotenone-treated rats. Histopathological analysis confirmed the preservation of neuronal integrity in the substantia nigra and cortical regions. These findings suggest that Cr(D-Phe)₃ mitigates Parkinsonism-associated neurodegeneration by reducing oxidative stress, suppressing neuroinflammation and preserving dopaminergic neuronal function. Cr(D-Phe)₃ holds promise as a potential therapeutic candidate for Parkinsonism, warranting further investigation.