补骨脂肝毒性及其减毒方法的研究进展

Research Progress on Hepatotoxicity of Buguzhi(Psoraleae Fructus)and Its Attenuation Methods

补骨脂因含香豆素类、黄酮类和单萜酚类等化学成分,具有抗肿瘤、抗氧化、抗菌、抗炎、调节雌激素水平、促进骨生长、神经保护等作用而广泛用于肾部疾病、脾胃病、肢体经络病、妇科病的治疗,是临床常用的传统“无毒”的补益类中药,但近年来,国家药品不良反应监测中心多次通报警示补骨脂相关制剂(如壮骨关节丸、仙灵骨葆胶囊、致康胶囊)引发的肝损伤问题,更有单味补骨脂引发肝损伤的临床病例报道,其肝损伤现象已成为当前行业研究的热点及难点,为补骨脂的临床安全用药带来极大挑战。课题组前期基于脂多糖模型证实了补骨脂具有特异质肝损伤的属性,并从体内外角度相互验证了补骨脂甲素、补骨脂乙素、补骨脂酚、补骨脂定或可通过调控PI3K-Akt信号通路、NF-κB信号通路、NLRP3信号通路等引发肝损伤。通过对近年来补骨脂肝毒性的相关文献进行整理、归纳,探讨引起补骨脂肝毒性的主要毒理机制,并总结了配伍减毒和炮制减毒对减轻补骨脂肝毒性的重要意义,为补骨脂的临床安全用药提供数据支撑。

Buguzhi(Psoraleae Fructus)is a traditional non-toxic Chinese medicine commonly used in clinic because pharmacological research shows that Buguzhi(Psoraleae Fructus)is widely used in the treatment of kidney diseases,spleen and stomach diseases,limb meridian diseases and gynecological diseases because it contains chemical components such as coumarins,flavonoids and monoterpenoids and has anti-tumor,anti-oxidation,anti-bacterial and anti-inflammatory effects,estrogen level regulation,bone growth promotion and neuroprotection.However,in recent years,the National Center for ADR Monitoring has repeatedly notified and warned the liver injury caused by related preparations of Buguzhi(Psoraleae Fructus),such as Zhuanggu Guanjie Pill(壮骨关节丸),Xianling Gubao Capsule(仙灵骨葆胶囊)and Zhikang Capsule(致康胶囊),and there are even clinical case reports of liver injury caused by single taste of Buguzhi(Psoraleae Fructus).The phenomenon of liver injury has become a hot and difficult point in the current industry research which has brought great challenges to the clinical safe use of Buguzhi(Psoraleae Fructus).Based on the lipopolysaccharide model,our research group confirmed that Buguzhi(Psoraleae Fructus)has the property of specific liver injury,and mutually verified that bavachin,corylifolinin,bakuchiol and psoralidin can induce liver injury by regulating PI3K-AKT signaling pathway,NF-κB signaling pathway and NLRP3 signaling pathway.Therefore,this paper sorted out and summarized the relevant literatures on hepatotoxicity of Buguzhi(Psoraleae Fructus)in recent years,discussed the main toxicological mechanisms of hepatotoxicity,and summarized the significance of compatibility and processing to reduce hepatotoxicity of Buguzhi(Psoraleae Fructus)to provide data support for clinical safe medication of Buguzhi(Psoraleae Fructus).