biostudies-literatureZang HJthe Yunnan Provincial Science and Technology DepartmentYunnan Characteristic Plant Screening and R&D Service CXO PlatformKey Research and Development Project of Yunnan ProvinceYATASthe National Natural Science Foundation of China67https://www.ebi.ac.uk/biostudies/studies/S-EPMC12484522biostudies-literatureUnknown15(1)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 = Natural products and bioprospectingNeuroprotective effects of chemical constituents from Nicotiana tabacum L. in Parkinson's disease.PMC12484522202201AS070040202203AC100009202003AD150012202302AA3100358229368320225300002410122022YKZY001Yin QYZang HJWang YCLiao XDi YTSui XYHao XJZhai XRBai XLWang YHXin ZQfalseNeuroprotective effects of chemical constituents from Nicotiana tabacum L. in Parkinson's disease.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 = 2025-01-01T00:00:00Z2025 Oct2026-06-04T00:36:21.167Z2026-05-03T03:12:30.3ZS-EPMC124845224102829810.1007/s13659-025-00541-8