AUTHOR=Zhang Qian , Wang Junsong , Liao Shanting , Li Pei , Xu Dingqiao , Lv Yan , Yang Minghua , Kong Lingyi TITLE=Optimization of Huang-Lian-Jie-Du-Decoction for Ischemic Stroke Treatment and Mechanistic Study by Metabolomic Profiling and Network Analysis JOURNAL=Frontiers in Pharmacology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00165 DOI=10.3389/fphar.2017.00165 ISSN=1663-9812 ABSTRACT=
Optimal drug proportions and mechanism deciphering of multicomponent drugs are critical for developing novel therapies to cope with complex diseases, such as stroke. In the present study, orthogonal experimental design was applied to explore the optimal proportion of the four component herbs in Huang-Lian-Jie-Du-Decoction (HLJDD) on the treatment of ischemic stroke. The treatment efficacies and mechanisms were assessed using global and amino acids (AAs) targeted metabolomics, as well as correlation network analysis. The global NMR metabolomics results revealed that AAs metabolism was significantly perturbed in middle cerebral artery occlusion rats. The levels of 23 endogenous AAs were then subjected to HPLC-QTOF-MS/MS analysis. These results complemented with neurobehavioral evaluations, cerebral infarct assessments, biochemical evaluations, histological inspections and immunohistochemistry observations strongly demonstrated that HLJDD with optimal proportion of 6 (