补骨脂潜在肝毒性的修制减毒方法研究:酒浸水漂法

Attenuating the potential hepatotoxicity of Psoraleae Fructus by pre-processing: the alcohol soaking and water rinsing method

近年来,补骨脂肝毒性问题引起高度重视,探索建立补骨脂减毒方法具有重要意义。本文基于《雷公炮炙论》对补骨脂修制前处理方法记载的酒浸水漂法,以3D培养的人源肝脏类器官为模型,结合高内涵成像技术来评价补骨脂不同修制品的减毒效果;同时以U*12(108)均匀设计法对补骨脂酒浸水漂法的修制工艺进行优化研究。结果表明:不同修制品对类器官模型的毒性表现出显著差异,其中酒精浓度、酒浸次数、酒浸料液比、水浸时间和水浸次数为独立显著因素(均P<0.01)。进一步基于回归建模预测最优减毒工艺并得到验证,最优减毒工艺为:酒精浓度80%、酒浸次数3次、酒浸料液比3倍、酒浸时间30 h、水浸料液比2倍、水浸次数3次、水浸时间12 h和蒸制时间5 h。本研究表明《雷公炮炙论》记载的酒浸水漂法可有效降低补骨脂的潜在肝毒性,从药材前处理为降低补骨脂肝损伤风险提供了参考依据。

Recently,the hepatotoxicity issue regarding to Psoraleae Fructus(PF)has attracted remarkable concerns,which highlights the urgent need to explore the toxicity attenuation method for PF.In this study,we proposed an alcohol soaking and water rinsing method for pre-processing PF based on the record in the classics-"Lei Gong Pao Zhi Lun",aiming to attenuate the potential hepatotoxicity of PF.The optimal pre-processing methods and parameters were investigated by U*12(10~8)uniform design coupled with 3 D-cultured human-derived liver organoids model and high-content imaging.The results showed that there were significant variations among the hepatotoxicity intensities of different pre-processed PF products.Four factors,including the concentration of alcohol,the ratio of material and alcohol in alcohol soaking,the time of alcohol soaking and the times of water rinsing,were found as independent significant factors(all P<0.01).The optimal pre-process parameters were further predicted and verified as follows:the alcohol concentration is 80%,the times of alcohol soaking is 3,the ratio of alcohol and material of alcohol soaking is 3,the time for alcohol soaking is 30 h,the ratio of water and material of water rinsing is 2,the times of water rinsing is 3,the time water rinsing is 12 h and the time of steaming is 5 h.This research demonstrated that the alcohol soaking and water rinsing method can effectively reduce the potential hepatotoxicity of PF.This method provides a reference for reducing the risk of PF liver injury from the perspective of Chinese medicinal materials pre-processing.