Huang Zhi-Qiang, Fan Xue-Mei, Wang Yi-Ming, Liang Qiong-Lin, Tong Xiao-Lin, Bai Yu, Li Ying-Meng, Luo Guo-An, Chen Chao
School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Key Laboratory of Bioorganic Phosphorus Chemistry &Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.
Acta Pharmacol Sin. 2017 Aug;38(8):1141-1149. doi: 10.1038/aps.2016.165. Epub 2017 Mar 20.
It is difficult to accurately evaluate the efficacy of traditional Chinese medicine (TCM), which leads to the uncertainty and complexity of dose-effect analysis. In this study we established the "Focus" mode of biomarkers to characterize the dose-effect relationship of Gegen Qinlian Decoction (GQD), a TCM formula for treating type 2 diabetes mellitus (2-DM). A rat model of 2-DM was established through high fat diet feeding combined with low-dose STZ injection. Rats with 2-DM were administered high, middle or low doses (6.785, 4.071, 1.357 mg·kg·d, respectively) of GQD extract for 60 d. Metformin (300 mg·kg·d) was taken as the positive control. Blood samples were collected to assess serum biochemical indexes and metabolic profiling. After "Focus" analysis, the biochemical index triglycerides (TG) and insulin sensitivity (ISI) were identified as focused integrated biomarkers (FIBs), while arachidonic acid and docosatetraenoic acid were the metabolic FIBs. Dose-effect relationship curves of GQD were built based on these types of FIBs. Furthermore, the two dose-effect relationship curves showed similar trends with the middle dosage displaying the greatest efficacy, suggesting that insulin function and arachidonic acid metabolism played important roles in 2-DM and the responses to GQD. The metabolic FIB docosatetraenoic should be further explored for understanding its involvement in the process of 2-DM occurrence and the treatment. This "Focus" mode provides a novel strategy to evaluate the dose-effect relationship of a TCM. The system and concepts established here may also be applicable for assessing the dose-effect relationships of Western medicines.
准确评估中药（TCM）的疗效具有一定难度，这导致了剂量效应分析的不确定性和复杂性。在本研究中，我们建立了生物标志物的“聚焦”模式，以表征葛根芩连汤（GQD，一种用于治疗2型糖尿病（2-DM）的中药方剂）的剂量效应关系。通过高脂饮食喂养联合低剂量链脲佐菌素注射建立2-DM大鼠模型。给患有2-DM的大鼠分别给予高、中、低剂量（分别为6.785、4.071、1.357 mg·kg·d）的GQD提取物，持续60天。以二甲双胍（300 mg·kg·d）作为阳性对照。采集血样以评估血清生化指标和代谢谱。经过“聚焦”分析，生化指标甘油三酯（TG）和胰岛素敏感性（ISI）被确定为聚焦整合生物标志物（FIBs），而花生四烯酸和二十二碳四烯酸为代谢FIBs。基于这些类型的FIBs构建了GQD的剂量效应关系曲线。此外，两条剂量效应关系曲线呈现相似趋势，其中中剂量显示出最大疗效，这表明胰岛素功能和花生四烯酸代谢在2-DM及对GQD的反应中发挥着重要作用。对于代谢FIB二十二碳四烯酸，应进一步探索以了解其在2-DM发生过程和治疗中的作用。这种“聚焦”模式为评估中药的剂量效应关系提供了一种新策略。这里建立的系统和概念也可能适用于评估西药的剂量效应关系。
