Wei Xin, Jiang Li-Ping, Guo Ying, Khan Afsar, Liu Ya-Ping, Yu Hao-Fei, Wang Bei, Ding Cai-Feng, Zhu Pei-Feng, Chen Ying-Ying, Zhao Yun-Li, Chen Yong-Bing, Wang Yi-Fen, Luo Xiao-Dong
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.
University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
Nat Prod Bioprospect. 2017 Oct;7(5):413-419. doi: 10.1007/s13659-017-0141-y. Epub 2017 Sep 26.
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 N -oxide (2), and 3β-sitsirikine N -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 N -oxide (2), isocorynoxeine (6), isorhynchophylline (7), (4S)-akuammigine N-oxide (8), and (4S)-rhynchophylline N-oxide (10) showed unexpected inhibitory activities at 10 μM. 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.
钩藤在中国通常被认为是治疗头晕、脑血管疾病和神经紊乱的传统药物。此前，已有大量关于钩藤生物碱神经保护活性的报道。在当前的研究中，从钩藤中分离出了三种新的吲哚生物碱（1-3），分别鉴定为鸡骨常山酸（1）、鸡骨常山酸N-氧化物（2）和3β-喜果宁碱N-氧化物（3），以及26种已知类似物。然而，在对所有分离出的化合物进行神经干细胞（NSCs）增殖试验时，鸡骨常山酸（1）、鸡骨常山酸N-氧化物（2）、异钩藤碱（6）、异钩吻素子（7）、（4S）-阿枯米京碱N-氧化物（8）和（4S）-钩吻素子N-氧化物（10）在10 μM时表现出意外的抑制活性。与之前的神经保护报道不同，作为一种警示，我们的发现揭示了钩藤可能存在神经干细胞毒性和神经损伤风险的线索，同时也讨论了分离出的化合物的构效关系。
