Li Yan, Wang Xin, Yang Zhe, Liao Nan-Xi, Wang Yi-Wei, Ji Chao-Fan, Li Shao
Xin'an Medical Research Center, Wannan Medical College, Anhui Famous Traditional Chinese Medicine LI Yan Studio Wuhu 241000, China.
Department of Automation, Tsinghua University, Institute for TCM-X Beijing 100084, China.
Zhongguo Zhong Yao Za Zhi. 2022 Oct;47(19):5264-5273. doi: 10.19540/j.cnki.cjcmm.20220613.704.
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 factor κB(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.
基于网络靶点方法与技术，本研究首次提出了一种针对中药方剂的新型优化方法。此外，以清络饮为例，开发了一种将科学方法与名老中医经验相结合的中药研发方法。具体而言，本研究基于清络饮的组成，运用药物作用网络靶点智能定量分析（UNIQ）预测针对类风湿关节炎（RA）关键通路如血管生成的药物。然后，结合首届全国名中医李济仁及爱辉名中医李岩的经验与中医理论，开发了一种新型的血管生成靶向方剂——改良清络饮（MQLD）。随后，对MQLD的临床疗效及作用机制进行了验证。结果显示，通过UNIQ鉴定出27种对血管生成相关关键信号通路有显著调节作用的药物，其中6种被中医师选中用于研发MQLD。临床试验表明，MQLD在改善美国风湿病学会20%和50%标准（ACR20、ACR50）或中医证候评价方面的临床疗效均优于清络饮。实验研究表明，MQLD可通过作用于血管内皮生长因子（VEGF）通路、核因子κB（NF-κB）通路、炎性细胞因子释放及免疫细胞调节来抑制RA血管生成。综上所述，本研究通过网络靶点技术研发出临床疗效提高、适用临床场景精准且已获专利授权的新方剂MQLD，为中药精准研发及名老中医经验传承提供了新途径。
