A new method to evaluate the dose-effect relationship of a TCM formula Gegen Qinlian Decoction: "Focus" mode of integrated biomarkers.
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-1·d-1, respectively) of GQD extract for 60 d. Metformin (300 mg·kg-1·d-1) 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.
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.|School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Guangzhou 510006, China.|Department of Pharmacy and Center for Computational Science and Engineering, National University of Singapore, 117542, Singapore.
Zhi-Qiang
ZQ
Huang
Key Laboratory of Bioorganic Phosphorus Chemistry &Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.
Xue-Mei
XM
Fan
Key Laboratory of Bioorganic Phosphorus Chemistry &Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.
Yi-Ming
YM
Wang
Key Laboratory of Bioorganic Phosphorus Chemistry &Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.
Qiong-Lin
QL
Liang
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
Xiao-Lin
XL
Tong
School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
Yu
Y
Bai
School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
Ying-Meng
YM
Li
Key Laboratory of Bioorganic Phosphorus Chemistry &Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.|State Key Laboratory for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China.
Guo-An
GA
Luo
School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.|School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Guangzhou 510006, China.|Department of Pharmacy and Center for Computational Science and Engineering, National University of Singapore, 117542, Singapore.
Chao
C
Chen
D000818:Animals; D016718:Arachidonic Acid / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D008516:Medicine, Chinese Traditional / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D014280:Triglycerides; D016718:Arachidonic Acid