活血化瘀类中药抗肝纤维化作用的计算药理探讨  

In Silico Pharmacology Study of Active Ingredients from Chinese Drugs for Activating Blood Circulation and Removing Stasis in Liver Fibrosis

作　　者：刘雪平[1] 杨琳琳[2] 付鹏[1] 唐凯临[3] 曹志伟[1,2,3] 

机构地区：[1]华东理工大学生物反应器工程国家重点实验室,上海200237 [2]同济大学生命科学与技术学院,上海200092 [3]上海生物信息技术研究中心,上海201203

出　　处：《生物物理学报》2012年第12期971-982,共12页Acta Biophysica Sinica

基　　金：国家自然科学基金项目(30900832);重大科技专项(2012ZX10005001-008);肝肾疾病病证教育部重点实验室(上海中医药大学)开放课题

摘　　要：如何防治肝纤维化是目前备受关注的问题,活血化瘀类中药治疗肝纤维化有良好的效果。研究发现,虽然活血化瘀类中药有效组分结构相似性不高,但是理化性质比较相似。与实验阶段药物和中药数据库中全部活性成分相比,活血化瘀类中药有效组分的化学空间分布更接近已知药物,约90%的有效组分符合Lipinski五规则。基于靶点蛋白作用通路的研究发现,活血化瘀中药通过直接作用或间接影响纤维化相关蛋白,并且多靶点多通路协同作用于多条生物路径,直接抑制TNF或间接调控NF-kappaB是其中典型的两条途径。这些研究结果可为阐明活血化瘀类中药的作用机制提供更多信息,有助于进一步筛选抗肝纤维化作用药物。It has been indicated by many studies that active ingredients from Chinese drugs for activating blood circulation and removing stasis are potential tools to protect liver from fibrosis. There are rare, yet common, effective compounds in different herbs activating blood and removing stasis. The structures of these effective ingredients are not similar, whereas the properties of them are more alike. Over 90% of the active ingredients obey Lipinski rule of five; they are closer to the approved drugs than to the experimental drugs and to the compounds in traditional Chinese medicine. In the present paper, we show the targets of the effective ingredients map to the core proteins in the fibrosis network. Furthermore, the regulated proteins of these effective ingredients synergistically affect multiple pathways. There are two typical approaches, such as inhibiting the TNF directly or decreasing the NF-kappaB indirectly. Presented results provide information illustrating the mechanism of Chinese drugs for activating blood circulation and removing stasis, and can further help in screening of the candidate drugs for liver fibrosis.

关 键 词：活血化瘀 肝纤维化 机制 

分 类 号：TQ461[化学工程—制药化工]