Metabolomics coupled with proteomics advancing drug discovery toward more agile development of targeted combination therapies.
To enhance the therapeutic efficacy and reduce the adverse effects of traditional Chinese medicine, practitioners often prescribe combinations of plant species and/or minerals, called formulae. Unfortunately, the working mechanisms of most of these compounds are difficult to determine and thus remain unknown. In an attempt to address the benefits of formulae based on current biomedical approaches, we analyzed the components of Yinchenhao Tang, a classical formula that has been shown to be clinically effective for treating hepatic injury syndrome. The three principal components of Yinchenhao Tang are Artemisia annua L., Gardenia jasminoids Ellis, and Rheum Palmatum L., whose major active ingredients are 6,7-dimethylesculetin (D), geniposide (G), and rhein (R), respectively. To determine the mechanisms underlying the efficacy of this formula, we conducted a systematic analysis of the therapeutic effects of the DGR compound using immunohistochemistry, biochemistry, metabolomics, and proteomics. Here, we report that the DGR combination exerts a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of hepatic injury. Thus, DGR synergistically causes intensified dynamic changes in metabolic biomarkers, regulates molecular networks through target proteins, has a synergistic/additive effect, and activates both intrinsic and extrinsic pathways.
National TCM Key Lab of Serum Pharmacochemistry, Key Lab of Chinmedomics, Heilongjiang University of Chinese Medicine and Key Pharmacometabolomic Platform of Chinese Medicines, Heping Road 24, Harbin 150040, China. xijunwangls@126.com
Xijun
X
Wang
Aihua
A
Zhang
Ping
P
Wang
Hui
H
Sun
Gelin
G
Wu
Wenjun
W
Sun
Haitao
H
Lv
Guozheng
G
Jiao
Hongying
H
Xu
Ye
Y
Yuan
Lian
L
Liu
Dixin
D
Zou
Zeming
Z
Wu
Ying
Y
Han
Guangli
G
Yan
Wei
W
Dong
Fangfang
F
Wu
Tianwei
T
Dong
Yang
Y
Yu
Shuxiang
S
Zhang
Xiuhong
X
Wu
Xin
X
Tong
Xiangcai
X
Meng
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D039823:Iridoids / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy*; D008297:Male; D008516:Medicine, Chinese Traditional; D055442:Metabolome; D055432:Metabolomics; D058990:Molecular Targeted Therapy; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D014468:Umbelliferones / Q000494:pharmacology
C012923:6,7-dimethylaesculetin; D000880:Anthraquinones; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; D039823:Iridoids; D020543:Proteome; D014468:Umbelliferones; C542425:yin-chen-hao-tang; C007835:geniposide; C020491:rhein