Indole Alkaloids Inhibiting Neural Stem Cell from Uncaria rhynchophylla

doi:10.1007/s13659-017-0141-y

Natural Products and Bioprospecting ›› 2017, Vol. 7 ›› Issue (5): 413-419.DOI: 10.1007/s13659-017-0141-y

• Original articles • Previous Articles

Indole Alkaloids Inhibiting Neural Stem Cell from Uncaria rhynchophylla

Xin Wei^1,2, Li-Ping Jiang^2,3, Ying Guo^1,2, Afsar Khan⁴, Ya-Ping Liu¹, Hao-Fei Yu^1,2, Bei Wang^1,2, Cai-Feng Ding^1,2, Pei-Feng Zhu^1,2, Ying-Ying Chen¹, Yun-Li Zhao¹, Yong-Bing Chen³, Yi-Fen Wang¹, Xiao-Dong Luo^1,5

1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China;
2. University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China;
3. Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, People's Republic of China;
4. Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan;
5. Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming 650201, People's Republic of China

Received:2017-08-04 Revised:2017-09-12 Online:2018-02-06 Published:2017-10-24
Supported by:
The authors are grateful to the National Natural Science Foundation of China (81225024, 31500292, 31770388) for financial support.

Indole Alkaloids Inhibiting Neural Stem Cell from Uncaria rhynchophylla

1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China;
2. University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China;
3. Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, People's Republic of China;
4. Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan;
5. Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming 650201, People's Republic of China

通讯作者: Yi-Fen Wang,e-mail:wangyifen@mail.kib.ac.cn;Xiao-Dong Luo,e-mail:xdluo@mail.kib.ac.cn
基金资助:
The authors are grateful to the National Natural Science Foundation of China (81225024, 31500292, 31770388) for financial support.

Abstract

Abstract: Uncaria rhynchophylla is commonly recognized as a traditional treatment for dizziness, cerebrovascular diseases, and nervous disorders in China. Previously, the neuro-protective activities of the alkaloids from U. rhynchophylla were intensively reported. In current work, three new indole alkaloids (1-3), identified as geissoschizic acid (1), geissoschizic acid N₄-oxide (2), and 3β-sitsirikine N₄-oxide (3), as well as 26 known analogues were isolated from U. rhynchophylla. However, in the neural stem cells (NSCs) proliferation assay for all isolated compounds, geissoschizic acid (1), geissoschizic acid N₄-oxide (2), isocorynoxeine (6), isorhynchophylline (7), (4S)-akuammigine N-oxide (8), and (4S)-rhynchophylline N-oxide (10) showed unexpected inhibitory activities at 10μM. Unlike previous neuro-protective reports, as a warning or caution, our finding showcased a clue for possible NSCs toxicity and the neural lesions risk of U. rhynchophylla, while the structure-activity relationships of the isolated compounds were discussed also.

Key words: Uncaria rhynchophylla, Indole alkaloids, NSCs proliferation

摘要： Uncaria rhynchophylla is commonly recognized as a traditional treatment for dizziness, cerebrovascular diseases, and nervous disorders in China. Previously, the neuro-protective activities of the alkaloids from U. rhynchophylla were intensively reported. In current work, three new indole alkaloids (1-3), identified as geissoschizic acid (1), geissoschizic acid N₄-oxide (2), and 3β-sitsirikine N₄-oxide (3), as well as 26 known analogues were isolated from U. rhynchophylla. However, in the neural stem cells (NSCs) proliferation assay for all isolated compounds, geissoschizic acid (1), geissoschizic acid N₄-oxide (2), isocorynoxeine (6), isorhynchophylline (7), (4S)-akuammigine N-oxide (8), and (4S)-rhynchophylline N-oxide (10) showed unexpected inhibitory activities at 10μM. Unlike previous neuro-protective reports, as a warning or caution, our finding showcased a clue for possible NSCs toxicity and the neural lesions risk of U. rhynchophylla, while the structure-activity relationships of the isolated compounds were discussed also.

关键词: Uncaria rhynchophylla, Indole alkaloids, NSCs proliferation

Xin Wei, Li-Ping Jiang, Ying Guo, Afsar Khan, Ya-Ping Liu, Hao-Fei Yu, Bei Wang, Cai-Feng Ding, Pei-Feng Zhu, Ying-Ying Chen, Yun-Li Zhao, Yong-Bing Chen, Yi-Fen Wang, Xiao-Dong Luo. Indole Alkaloids Inhibiting Neural Stem Cell from Uncaria rhynchophylla[J]. Natural Products and Bioprospecting, 2017, 7(5): 413-419.

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Indole Alkaloids Inhibiting Neural Stem Cell from Uncaria rhynchophylla

Indole Alkaloids Inhibiting Neural Stem Cell from Uncaria rhynchophylla

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