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

doi:10.1007/s13659-025-00541-8

Natural Products and Bioprospecting ›› 2025, Vol. 15 ›› Issue (6): 67-67.DOI: 10.1007/s13659-025-00541-8

• Original Article • Previous Articles Next Articles

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

Hao-Jing Zang^1,3,4, Xiao-Lin Bai^2,4, Xue-Yi Sui⁵, Xiao-Rui Zhai^2,4, Yong-Cui Wang¹, Zhong-Quan Xin¹, Qiu-Yuan Yin³, Xiao-Jiang Hao^1,6,7, Yue-Hu Wang⁸, Xun Liao², Ying-Tong Di¹

1. State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China;
2. Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, China;
3. School of Life Sciences, Yunnan University, Kunming, 650091, China;
4. University of Chinese Academy of Sciences, Beijing, 100049, China;
5. National Tobacco Genetic Engineering Research Centre, Yunnan Academy of Tobacco Agricultural Sciences, Kunming, 650021, China;
6. Research Unit of Chemical Biology of Natural Anti-Virus Products, Chinese Academy of Medical Sciences, Beijing, 100730, China;
7. Yunnan Characteristic Plant Extraction Laboratory, Kunming, 650201, China;
8. Yunnan Key Laboratory for Wild Plant Resources, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China

Received:2025-06-13 Online:2026-01-12
Contact: Yue-Hu Wang Email:E-mail:wangyuehu@mail.kib.ac.cn
Supported by:
This work was supported by the Project of YATAS (2022530000241012), Yunnan Characteristic Plant Screening and R&D Service CXO Platform (2022YKZY001), Key Research and Development Project of Yunnan Province (202203AC100009), the National Natural Science Foundation of China (82293683), and the Yunnan Provincial Science and Technology Department (202003AD150012 to Xiao-Jiang Hao, 202201AS070040 and 202302AA310035 to Ying-Tong Di).

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

Hao-Jing Zang^1,3,4, Xiao-Lin Bai^2,4, Xue-Yi Sui⁵, Xiao-Rui Zhai^2,4, Yong-Cui Wang¹, Zhong-Quan Xin¹, Qiu-Yuan Yin³, Xiao-Jiang Hao^1,6,7, Yue-Hu Wang⁸, Xun Liao², Ying-Tong Di¹

1. State Key Laboratory of Phytochemistry and Natural Medicines, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China;
2. Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, China;
3. School of Life Sciences, Yunnan University, Kunming, 650091, China;
4. University of Chinese Academy of Sciences, Beijing, 100049, China;
5. National Tobacco Genetic Engineering Research Centre, Yunnan Academy of Tobacco Agricultural Sciences, Kunming, 650021, China;
6. Research Unit of Chemical Biology of Natural Anti-Virus Products, Chinese Academy of Medical Sciences, Beijing, 100730, China;
7. Yunnan Characteristic Plant Extraction Laboratory, Kunming, 650201, China;
8. Yunnan Key Laboratory for Wild Plant Resources, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China

通讯作者: Yue-Hu Wang Email:E-mail:wangyuehu@mail.kib.ac.cn
作者简介:Xun Liao Email:E-mail:liaoxun@cib.amc.cn;Ying-Tong Di Email:E-mail:diyt@mail.kib.ac.cn
基金资助:
This work was supported by the Project of YATAS (2022530000241012), Yunnan Characteristic Plant Screening and R&D Service CXO Platform (2022YKZY001), Key Research and Development Project of Yunnan Province (202203AC100009), the National Natural Science Foundation of China (82293683), and the Yunnan Provincial Science and Technology Department (202003AD150012 to Xiao-Jiang Hao, 202201AS070040 and 202302AA310035 to Ying-Tong Di).

Abstract

Abstract: 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 (K_i = 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).

Key words: Parkinson's disease, neuroprotective effects, Nicotiana tabacum L, 21-norditerpenoid

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 (K_i = 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).

关键词: Parkinson's disease, neuroprotective effects, Nicotiana tabacum L, 21-norditerpenoid

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. Neuroprotective effects of chemical constituents from Nicotiana tabacum L. in Parkinson’s disease[J]. Natural Products and Bioprospecting, 2025, 15(6): 67-67.

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

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

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