Pang Su-Qiu, Wang Guo-Quan, Lin Jun-sheng, Diao Yong, Xu Rui-an
School of Biomedical Sciences, Huaqiao University , Quanzhou , China and.
Pharm Biol. 2014 Oct;52(10):1315-9. doi: 10.3109/13880209.2014.891139. Epub 2014 Jul 3.
Broussonetia papyrifera (L.) Vent. (Moraceae), a traditional Chinese medicinal herb, has been extensively applied for many years to treat various diseases. Recently, a number of compounds with biological and pharmacological activities have been extracted from the plant and used as chemotherapeutic candidates to treat a range of diseases such as cancer.
The current study was designed to isolate the alkaloid compounds from ethyl acetate extraction of Broussonetia papyrifera fruits, and to evaluate the cytotoxic activity of total alkaloids as well as individual isoquinoline alkaloids from B. papyrifera fruits.
Alkaloid compounds were isolated from the ethyl acetate extraction by silica gel column chromatography methods using CHCl3/MeOH as eluents. The compounds' structures were determined by detailed analysis of NMR, MS spectral data, and chemical methodology. Cytotoxic activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methods against human A375, Hela, BEL-7402 cancer cells, and non-cancer cells.
Two isoquinonline alkaloids were isolated and characterized as N-norchelerythrine and dihydrosanguinarine. The total alkaloids and seven individual alkaloids had higher activities on BEL-7402 and Hela cell lines with low IC50 values 6.61-47.41 and 5.97-40.17 μg/mL (<50 μg/mL). Nitidine, broussonpapyrine, and chelerythrine had strong toxic on non-cancer cells with IC50 value 18.01, 19.91, and 22.31 μg/mL, respectively.
N-Norchelerythrine and dihydrosanguinarine were isolated from this plant for the first time. Our data implicated that seven isoquinoline alkaloids had cytotoxity with structure-activity relationships, which provided fundamental information for further modification of their anticancer effect.
构树（桑科）是一种传统的中药材，多年来已被广泛应用于治疗各种疾病。最近，已从该植物中提取出许多具有生物和药理活性的化合物，并用作治疗一系列疾病（如癌症）的化疗候选药物。
本研究旨在从构树果实的乙酸乙酯提取物中分离生物碱化合物，并评估总生物碱以及构树果实中单个异喹啉生物碱的细胞毒性活性。
采用硅胶柱色谱法，以CHCl3/MeOH为洗脱剂，从乙酸乙酯提取物中分离生物碱化合物。通过对NMR、MS光谱数据和化学方法的详细分析确定化合物的结构。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法评估对人A375、Hela、BEL-7402癌细胞和非癌细胞的细胞毒性活性。
分离并鉴定出两种异喹啉生物碱，分别为N-去甲白屈菜红碱和二氢血根碱。总生物碱和七种单一生物碱对BEL-7402和Hela细胞系具有较高活性，IC50值较低，分别为6.61 - 47.41和5.97 - 40.17μg/mL（<50μg/mL）。氧化两面针碱、构树碱和白屈菜红碱对非癌细胞具有较强毒性，IC50值分别为18.01、19.91和22.31μg/mL。
首次从该植物中分离出N-去甲白屈菜红碱和二氢血根碱。我们的数据表明，七种异喹啉生物碱具有细胞毒性，存在构效关系，这为进一步改善其抗癌效果提供了基础信息。
