补骨脂肝损伤机制及减毒方法研究进展

Research Progress on Hepatotoxicity Mechanism and Attenuation Methods of Psoraleae Fructus

补骨脂为豆科植物补骨脂Psoralea corylifolia的干燥成熟果实。性温,味辛、苦,归肾、脾经。主要功效为温肾助阳、纳气平喘、温脾止泻等;外用可消风祛斑。临床上主要用于治疗肾虚阳痿、腰膝酸软冷痛、白癜风等。目前已有的研究表明补骨脂具有抗肿瘤、抗氧化、抗菌、抗炎、促进骨骼生长、保护心血管等多种药理作用。但同时,较多的国内外研究发现,长时间或大剂量服用补骨脂及其复方可导致肝损伤、光损伤、肾损伤等,其中最为常见的则是补骨脂致肝损伤,关于补骨脂致损伤的临床报道大部分均为致药物性肝损伤事件,这使得补骨脂在临床中的使用受到了限制,从而不能很好地发挥其应有的治疗作用。因此,充分了解补骨脂产生肝损伤的机制及减毒方法尤为重要。该文通过查阅近年来国内外报道补骨脂产生肝损伤的相关文献,对补骨脂致肝损伤临床报道、肝损伤成分、毒理机制及减毒方法 4个方面进行综述,分别从胆汁酸淤积、氧化应激反应、线粒体损伤、肝脂肪变形等方面对补骨脂的肝损伤进行了论述,并从配伍减毒与炮制减毒等方面对补骨脂致肝损伤的减毒方法进行总结,旨在全面客观地阐明补骨脂致肝损伤的潜在机制和减毒方面的研究进展,以期为补骨脂致肝损伤的进一步研究及临床合理用药提供理论依据。

Psoraleae Fructus is the dried and mature fruit of the legume Psoralea corylifolia. It is warm in nature,pungent and bitter in flavor,and attributive to the kidney and spleen meridians. Its main effect include warming the kidney and assisting Yang,absorbing Qi and relieving asthma,warming the spleen and relieving diarrhea,etc.,and it also can for external use of eliminating wind and freckle. Clinically,Psoraleae Fructus is mainly used for the treatment of impotence due to kidney deficiency,soreness of waist and knees,vitiligo,etc.The existing studies have shown that Psoraleae Fructus has a variety of pharmacological effect,such as antitumor,anti-oxidant,anti-bacterial,anti-inflammatory,promoting bone growth and protecting cardiovascular.But at the same time,many studies at home and abroad have found that taking Psoraleae Fructus and its compounds for a long time or in large doses can cause liver toxicity,phototoxicity,nephrotoxicity,etc. The most common is liver toxicity,most of the clinical reports on the toxicity of psoralen are caused by drug-induced liver injury events,which limits the clinical use of Psoraleae Fructus and can’t exert its proper therapeutic effect.Therefore,it is particularly important to fully understand the toxicological mechanism of liver injury caused by Psoraleae Fructus and its attenuation methods. In this paper,by consulting the domestic and foreign related literatures in recent years that reported the hepatotoxicity of Psoraleae Fructus,the four aspects of clinical report on liver injury, hepatotoxic components, toxicological mechanisms and attenuation methods of Psoraleae Fructus were reviewed,including bile acid stasis and oxidative stress. The hepatotoxicity of Psoraleae Fructus was discussed in terms of reaction,mitochondrial damage,liver fat deformation,etc.,and the attenuation methods of Psoraleae Fructus were summarized from the aspects of compatibility attenuation and processing attenuation,aiming to comprehensively and objectively clarify Psoraleae Fructus. The potential toxicological mechanism of lipid-induced hepatotoxicity and research progress in attenuation were expected to provide a theoretical basis for further study of Psoraleae Fructus hepatotoxicity and clinical rational use of drugs.