目的 考察经不同方法炮制前后补骨脂中补骨脂甲素（bavachin，BC）、补骨脂二氢黄酮甲醚（bavachinin，BVC）、补骨脂酚（bakuchiol，BAK）3种手性成分含量变化的差异，并结合分子对接技术初步明确此3种手性成分的对映异构体在毒性机制上的潜在差异。方法 采用高效液相色谱-手性固定相（high performance liquid chromatography-chiral stationary phase，HPLC-CSP）法，通过改变流动相的比例，建立了补骨脂中3种手性成分的最佳分离方法，并比较来源于河南、四川、云南、辽宁4个产地的补骨脂经清炒法、盐炙法、酒浸法炮制前后各个对映异构体的含量差异。以前期筛选出的补骨脂致肝毒性作用靶标原癌基因酪氨酸激酶ABL1（Abelson tyrosine-protein kinase ABL1，ABL1）为对接主体，利用AutoDock Tools 1.5.7软件，对各个对映异构体分别进行分子对接。结果 采用Chiralpak IG色谱柱（250 mm×4.6 mm，5 µm），在以乙腈-纯水（50∶50）为流动相，体积流量为0.5 mL/min，柱温为35 ℃的条件下，实现了补骨脂中各个对映异构体的最佳分离。在4个产地的补骨脂生品中，(R)-BC、(S)-BVC、(S)-BAK为其主要构型，经清炒法、盐炙法、酒浸法炮制后，(R)-BC含量降低，(S)-BC含量升高，(R)-BVC、(S)-BAK的含量降低率分别高于其S、R构型。分子对接结果显示，(R)-BC、(R)-BVC、(S)-BAK与毒性靶标的结合能力分别强于其对映异构体。结论 补骨脂中3种手性成分的对映异构体的含量存在显著差异，经不同方法炮制后其含量变化也呈现明显区别，表明清炒法、盐炙法、酒浸法均能对补骨脂起到减毒作用。各个对映异构体与毒性靶标的相互作用能力及作用强度存在立体选择性差异。

Objective The content changes of bavachin (BC), bavachinin (BVC), and bakuchiol (BAK) in Buguzhi (Psoraleae Fructus, PF) before and after processing with different methods were investigated to preliminarily identify the potential differences in the toxicity mechanism of the enantiomers of these three chiral components combined with molecular docking technology. Methods The best separation method of three chiral components in PF was established based on high performance liquid chromatography-chiral stationary phase (HPLC-CSP) method by changing the proportion of mobile phase, and the contents of each enantiomer of PF from Henan, Sichuan, Yunnan and Liaoning were compared before and after the stri-frying, salt-roasting and wine immersion. Abelson tyrosine-protein kinase ABL1 (ABL1), a previously screened target of hepatotoxicity induced by PF, was used as the docking body, and the molecular docking of the three chiral compounds enantiomers was carried out separately by using AutoDock Tools 1.5.7. Results The optimum separation of each enantiomer in PF was achieved on Chiralpak IG column (250 mm × 4.6 mm, 5 µm) with acetonitrile-pure water (50:50) as the mobile phase at a flow rate of 0.5 mL/min and column temperature of 35 ℃. (R)-BC, (S)-BVC and (S)-BAK were the main configurations of the PF from the four producing areas. After being processed by stri-frying, salt-roasting, and wine immersion, the content of (R)-BC was reduced, the content of (S)-BC was elevated, and the content reduction rates of (R)-BVC and (S)-BAK were higher than those of their S and R conformations, respectively. Molecular docking results showed that (R)-BC, (R)-BVC and (S)-BAK had stronger binding ability to toxic targets than their enantiomers, respectively. Conclusion There were significant differences in the contents of enantiomers of the three chiral components in PF, and the changes of the contents were also obvious after different processing methods, which indicated that stri-frying, salt-roasting and wine immersion methods could reduce the toxicity of PF. There were stereoselective differences in the interaction ability and intensity of each enantiomer with the toxic target.

R283.6

国家自然科学基金资助项目（82204760）；天津市科技局重大专项与工程计划项目（21ZXJBSY00040）