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<p>Parkinson’s disease (PD), the second most common neurodegenerative disorder globally, arises from selective dopaminergic neuron degeneration. While current therapies address symptoms, disease-modifying agents remain an unmet need. Herein, we investigated <i>Nicotiana tabacum</i> L. (Solanaceae), a plant linked epidemiologically to reduced PD risk, as a source of multi-target neuroprotective compounds. From ultra-low nicotine (&lt; 0.04%) tobacco leaves, we isolated 22 molecules, including a novel 21-norsesterterpenoid (Nicotiazanorpenoid A) and eight previously unreported compounds. Systematic evaluation revealed three synergistic neuroprotective mechanisms: (1) Antioxidant activity: Scopoletin (<b>3</b>) and isoferulic acid (<b>6</b>) showed significant radical scavenging capacity (ABTS assay; IC<sub>50</sub> = 27.74, and 18.13&#xa0;μM, respectively); (2) Neuronal protection: <i>cis</i>-11,14,17-Eicosatrienoic acid methyl ester (<b>14</b>) enhanced survival (93.94% vs. control) in 6-OHDA-induced PC12 cells, surpassing rasagiline (88.36% at equivalent concentrations); (3) MAO-B inhibition: five compounds displayed selective inhibition, with scopoletin (<b>3</b>) exhibiting highest potency (<i>K</i><sub>i</sub> = 20.7&#xa0;μM). Notably, plant prostaglandins (<b>10/11</b>) were identified as competitive MAO-B inhibitors first time through molecular docking and 100-ns MD simulations, revealing stable binding at the FAD site (ΔG = − 10.42, and − 9.75&#xa0;kcal/mol, respectively).</p> Graphical Abstract <p></p>

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Neuroprotective effects of chemical constituents from Nicotiana tabacum L. in Parkinson’s disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月1日

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  • Hao-Jing Zang,
  • Xiao-Lin Bai,
  • Xue-Yi Sui,
  • Xiao-Rui Zhai,
  • Yong-Cui Wang,
  • Zhong-Quan Xin,
  • Qiu-Yuan Yin,
  • Xiao-Jiang Hao,
  • Yue-Hu Wang,
  • Xun Liao,
  • Ying-Tong Di

摘要

Parkinson’s disease (PD), the second most common neurodegenerative disorder globally, arises from selective dopaminergic neuron degeneration. While current therapies address symptoms, disease-modifying agents remain an unmet need. Herein, we investigated Nicotiana tabacum L. (Solanaceae), a plant linked epidemiologically to reduced PD risk, as a source of multi-target neuroprotective compounds. From ultra-low nicotine (< 0.04%) tobacco leaves, we isolated 22 molecules, including a novel 21-norsesterterpenoid (Nicotiazanorpenoid A) and eight previously unreported compounds. Systematic evaluation revealed three synergistic neuroprotective mechanisms: (1) Antioxidant activity: Scopoletin (3) and isoferulic acid (6) showed significant radical scavenging capacity (ABTS assay; IC50 = 27.74, and 18.13 μM, respectively); (2) Neuronal protection: cis-11,14,17-Eicosatrienoic acid methyl ester (14) enhanced survival (93.94% vs. control) in 6-OHDA-induced PC12 cells, surpassing rasagiline (88.36% at equivalent concentrations); (3) MAO-B inhibition: five compounds displayed selective inhibition, with scopoletin (3) exhibiting highest potency (Ki = 20.7 μM). Notably, plant prostaglandins (10/11) were identified as competitive MAO-B inhibitors first time through molecular docking and 100-ns MD simulations, revealing stable binding at the FAD site (ΔG = − 10.42, and − 9.75 kcal/mol, respectively).

Graphical Abstract