- 概述
佛手柑素(bergamottin)，别名佛手柑亭、香柠檬亭、香柠檬素，存在于佛手、柚类、葡萄柚等柑橘属水果以及一些传统中 药材如羌活中，不溶于水，能溶于甲醇、乙醇、乙酸乙酯等有机溶剂。佛手柑素是一种天然的呋喃香豆素类化合物，然而市面上高纯度佛手柑素售价昂贵且稀少，因此绝大多数活性研究仅限于体外细胞实验，进一步的体内代谢研究却相对较少。关于“从天然植物中快速有效地提取分离纯化佛手柑素”的研究也少见报道。柚子是我国南方地区盛产的一种水果，然而占整果43％～48％的柚皮在鲜食或食品加工过程中却通常被丢弃，这不仅造成严重的资源浪费，还导致环境污染。研究从柚皮中提取高纯度的佛手柑素，可进一步加强柚皮资源的开发利用，降低生产成本，提高原料利用率，并为佛手柑素的药学活性研究及其相关作用机理研究提供工作基础和技术支持，最大程度地提高柚子的附加值。
- 生物活性
Bergamottin 是一种有效的竞争性 CYP1A1 抑制剂，Ki 为 10.703 nM。
- 靶点
CYP1A1
10.703 nM (Ki)
CYP1A1
0.192 μM (IC
50
)
CYP1A2
5.077 μM (IC
50
)
CYP2B2
4.535 μM (IC
50
)
CYP2B1
9.495 μM (IC
50
)
- 体外研究
Bergamottin is a competitive inhibitor of CYP1A1. Bergamottin inhibits CYP1A1, CYP1A2, CYP2B1, and CYP2B2 with IC
50
s of 0.192±0.029 μM, 5.077±0.31 μM, 9.495±0.979 μM, 4.535±0.092 μM, respectively. Bergamottin has potent antiproliferative effects on the A549 cells. Bergamottin shows both concentration-dependent as well as time‑dependent growth inhibitory effects against these cells. Bergamottin also inhibits the clonogenic activity of the A549 cancer cells by reducing the number of cancer colony forming cells. A reduction in clonogenicity also follows the concentration dependence on Bergamottin.
- 体内研究
The anticancer efficacy of Bergamottin under in vivo conditions using female BALB/c nude mice (a total of 20 mice are used) is determined. Tumors are induced in the mice by injecting non-small cell lung cancer A549 cells (1×10
6
cells/mouse). After tumor formation, the mice are sacrificed and tumors are removed and their weights and volumes are calculated. The results show that 25, 50 and 100 mg/kg Bergamottin injection reduce the tumor weight from 1.61 g in the PBS-treated group (control) to 1.21, 0.42 and 0.15 g, respectively. Tumor weight in the nude mice is reduced much more significantly in the highest-concentration Bergamottin group (100 mg/kg body weight) compared with the vehicle group (P<0.05). Likewise, 25, 50 and 100 mg/kg Bergamottin injection reduces the tumor volume from 2.2 cm
3
in the PBS-treated group (control) to 1.71, 1.1 and 0.51 cm3, respectively. The periodic measurement of the tumor xenograft volume indicates that the tumor volume in the nude mice is reduced considerably in the highest-concentration Bergamottin group (100 mg/kg body weight) compared with the vehicle group (P<0.05).
- 化学性质
白色针状结晶，可溶于甲醇、乙醇、DMSO等有机溶剂，来源于柠檬果肉中的含量最高，北沙参、羌活。
- 佛手柑素具有镇咳，平喘，祛痰的作用。
- 用于含量测定/鉴定/药理实验等。
药学活性研究表明，佛手柑素能使细胞色素P450酶系中多种药物代谢相关酶失活，从而影响胃肠道对药物的吸收，增加口服药物的生物利用度。此外，佛手柑素还能抑制癌细胞的增殖、侵袭和迁移，具有抗癌、抗菌、防诱变等多种生物学活性，受到广泛关注。
提取方法：以柚皮为原料，采用有机溶剂（甲醇、乙醇、乙酸乙酯等）提取，因高纯度佛手柑素售价昂贵且稀少，需优化提取工艺以提高原料利用率；来源包括佛手、柚类、葡萄柚等柑橘属水果及北沙参、羌活等中药材，柠檬果肉中含量最高。
