基于网络靶标建立名医验方优化的新方法:以“清络饮”优化开发为例

A new approach for optimizing empirical prescriptions of famous physicians based on network target:taking Qingluo Decoction as an example

该文首次提出基于网络靶标理论与技术的名医临床验方优化开发新方法,并以“清络饮”优化与开发为范例,建立一种科学手段与人用经验有机结合的中医药精准研发新途径。该研究以清络饮组方为基础,利用该课题组自主研发的网络靶标分析专利技术UNIQ(using network target for intelligent and quantitative analysis on drug actions)系统,从现有中药中全面预测出能够靶向类风湿性关节炎(rheumatoid arthritis,RA)血管新生等关键信号通路的备选中药,结合首届国医大师李济仁、安徽省名中医李艳学术经验从中医理论角度遣方组药,优化开发出一种靶向RA血管新生的新处方“加味清络饮”,进而验证加味清络饮的临床疗效与作用机制。结果显示,通过UNIQ系统预测出27味对RA血管新生等关键信号通路具有调节作用的备选中药,其中6味中药被名医按照中医理论选择而获得加味清络饮新组方;临床试验结果显示,加味清络饮在美国风湿病学会RA疾病缓解标准(American college of rheumatology 20、50 criteria,ACR20、ACR50)、中医证候疗效评价等方面的临床疗效均优于清络饮;机制研究结果显示,加味清络饮可靶向血管内皮生长因子VEGF信号转导通路、NF-κB通路、炎症细胞因子释放、免疫调节等不同通路,发挥抑制RA炎症反应、血管新生的网络调节机制。该研究靶向RA特定生物网络对名方进行精准优化,研制出了临床疗效提升、临床定位较为清晰、并获专利授权的加味清络饮新方,为名医经验传承发展和中药精准研发提供了新的思路和途径。

Based on the network target approach and technology,this study proposed for the first time a novel optimization method for Chinese medicine formulae.Moreover,with Qingluo Decoction as an example,a method for the research and development of Chinese medicine,which combines scientific methodology and experience of famous doctors,was developed.Specifically,based on the composition of Qingluo Decoction,this study used the using network target for intelligent and quantitative analysis on drug actions(UNIQ)to predict the medicinals that targeted the key pathways of rheumatoid arthritis(RA)such as angiogenesis.Then,combining the experience of the first national Chinese medical master LI Ji-ren and Aihui famous Chinese medicine doctor LI Yan and Chinese medicine theory,this study developed a novel angiogenesis-targeted prescription modified Qingluo Decoction(MQLD).Afterward,the clinical efficacy and mechanism of MQLD were verified.The results showed that 27 medicinals with significant regulatory effect on angiogenesis-related key signaling pathways were identified by UNIQ,among which 6 were selected by the Chinese medicine physicians to develop the MQLD.Clinical trials demonstrated that the clinical efficacy of MQLD,in terms of either American College of Rheumatology 20%improvement and 50%improvement criteria(ACR20,ACR50)or TCM syndrome evaluation,was better than that of Qingluo Decoction.Experimental study revealed that MQLD can inhibit RA angiogenesis by acting on the vascular endothelial growth factor(VEGF)pathway,nuclear factorκB(NF-κB)pathway,inflammatory cytokine release,and immune cell regulation.Taken together,this study developed a new formula MQLD with improved clinical efficacy,precise applicable clinical settings,and authorized patent through the network target technology,thus providing a new way for the precise development of Chinese medicine and preservation of the experience of famous physicians.