诃子在防治肝病蒙药复方中对其他药材的药效和药代动力学影响研究

The dried fruit of Terminalia chebula (fructus chebulae), known as the “King of Mongolian medicines”, is the most frequently used herbal drug in traditional Mongolian medicine prescriptions. In addition to its therapeutic effects, fructus chebulae was believed in Mongolian medicinal system to have abilities to reconcile multiple medicines in prescriptions. Safflower-7 is one of the most frequently used traditional Mongolian prescriptions for liver diseases. Previous researches revealed the structures of the major chemical constituents of Safflower-7. However, the chemical constituents of the monarch and other important medicines in Safflower-7 showed little activity against the replication enzymes of hepatitis C virus, i.e. the bioactive constituent groups are not clear and the effects of fructus chebulae on other medicines have not been clarified. Literature reported that safflower was effective in promoting blood circulation and removing blood stasis, which is beneficial for the prevention and treatment of various liver diseases. Inspired by the reports, we intend to explore the active constituents against blood stasis from both cell and animal experiments, to assess the influence of fructus chebulae on the chemical constituents of other component medicines in the view of pharmacodynamic and pharmacokinetic properties, to investigate whether the chemical constituents of fructus chebulae and other medicines in the prescriptions have synergistic effects, whether fructus chebulae can increase the bioavailability of the chemical constituents of other main medicines in the prescription. Overall, this study will use modern pharmacological and pharmacokinetic methods to interpret the scientific connotation of the traditional Mongolian prescription for liver diseases, to find out the groups of bioactive constituents, and to illustrate how fructus chebulae plays an important coordinating role in the traditional Mongolian prescription for liver diseases.

诃子是蒙药复方中使用率最高的药材,被称为“蒙药之王”,除其本身的药效外,蒙医还认为诃子有调节诸药的功能。红花-7味是蒙医治疗肝病的传统复方,目前研究基本明确了该复方的主要成分,但没有发现君药-红花有明显的抗丙肝病毒繁殖酶活性,没有阐明该复方的有效成分组及诃子对其他药材的调节作用。文献报道,缓解肝血瘀阻可防治多种肝病,红花传统用于活血化淤,近年药理学研究也证明了该作用。课题申请人从这些报道中受到启发,拟从细胞水平及动物水平研究该复方的活血化淤活性成分,进而从药效学及药代动力学两方面研究诃子对其他诸药的影响,探讨诃子成分是否与复方中其他药材的有效成分有协同作用,是否可以增加其他有效成分的生物利用度等,通过大量实验,发现复方的有效成分组,用现代药理学和药代动力学方法,诠释蒙药复方红花-7味在防治肝病中的科学原理并揭示蒙药之王-诃子在其中的作用。

诃子是蒙药复方中使用率最高的药材，被称为“蒙药之王”，除其本身的药效外，蒙医还认为诃子有调节诸药的功能。在国家自然科学基金资助下，本项目对红花7味（G-7）为代表的防治肝病蒙药复方有效成分、生物活性、药代动力学性质及诃子对其它药材的影响进行了研究。结果显示，羟基红花黄色素A能够促进血液循环、加速肝毒性物质排泄。诃子对G-7的组成药材红花、蓝盆花、麻黄等的主要成分在药效及药代动力学性质方面均有影响。在药效方面，诃子成分不仅可以增加G-7复方一些成分的作用也与临床西药5-氟尿嘧啶有协同作用，增强其抑制HepG2细胞的作用。另外，诃子成分可与麻黄碱生成新的缩合物，该缩合物有保肝作用而血脑屏障通透性减弱，提示其中枢神经兴奋副作用较麻黄碱弱。药代动力学方面，诃子对G-7药材的主要成分在体内分布及药代动力学性质方面有影响。诃子复合红花可在较短时间内使肝脏中羟基红花黄色素A达到浓度峰值；诃子配伍麻黄，使麻黄碱的达峰时间变长且血药浓度峰值减小，作用时间延长。另外，诃子酸有显著的抗氧化保肝作用等。以上结果展示了蒙药G-7复方的科学性，同时也对选择性研发针对不同类型肝病的现代药物提供了参考。