基于雷公法结合盐炙法对补骨脂的炮制及肝毒性评价

目的 基于雷公法结合盐炙法对补骨脂进行炮制减毒并评价补骨脂炮制前后的肝毒性变化。方法 建立高效液相色谱法同时测定补骨脂中补骨脂素、异补骨脂素、新补骨脂异黄酮、补骨脂甲素、补骨脂乙素和补骨脂酚6个指标成分的含量；选取醇浓度、醇浸时间和蒸制时间为考察因素，以指标成分含量下降率的综合加权评分为指标，正交试验优化炮制工艺，并通过小鼠肝毒性实验评价补骨脂炮制前后的肝毒性。结果 补骨脂最佳炮制工艺，按《中国药典》2020年版盐炙法制备盐补骨脂，取盐补骨脂适量，加入5倍量80%乙醇浸泡24 h，倒出乙醇并用蒸馏水洗净，加入5倍量蒸馏水，浸泡12 h，倒出蒸馏水并洗净，置蒸锅内隔水蒸4 h，取出晾干；由该法炮制所得的补骨脂炮制品中毒性成分含量明显下降，小鼠肝毒性显著降低。结论 该炮制方法可明显降低补骨脂的肝毒性，为临床合理炮制补骨脂提供参考。

Processing of Psoraleae Fructus based on combination of Leigong method and salt processed method and its hepatotoxicity evaluation

Objective Buguzhi (Psoraleae Fructus, PF) was processed based on combination of Leigong method and salt processed method, and the hepatotoxicity of PF before and after processing were evaluated. Methods An HPLC method was established for simultaneous determination of 6 index components (psoralen, isopsoralen, neobavaisoflavone, bavachin, isobavachalcone and bakuchiol) in PF. With alcohol concentration, alcohol soaking time and steaming time as the investigation factors, the processing technology was optimized by orthogonal test with the comprehensive weighted score of the decrease rate of index components content as the index, and the hepatotoxicity of PF before and after processing was evaluated by hepatotoxicity test in mice. Results The optimal processing technology was as follows:the salt-processed PF was prepared according to the Chinese Pharmacopoeia, and then was soaked in 5 times the amounts of 80% medicinal ethanol for 24 h. After removing the medicinal ethanol and washing with distilled water, the PF was further soaked in 5 times the amounts of distilled water for 12 h. After removing the distilled water and washing with fresh distilled water, the PF was steamed in a steamer for 4 h and then air-dried. The content of toxic components in the processed PF were significantly reduced, and hepatotoxicity in mice was significantly reduced. Conclusion The processing method can significantly reduce the hepatotoxicity of PF, and provide reference for rational clinical processing of PF.