title: Optimization of Huang-Lian-Jie-Du-Decoction for Ischemic Stroke Treatment and Mechanistic Study by Metabolomic Profiling and Network Analysis.
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 (Rhizoma coptidis): 4 (Radix scutellariae): 1 (Cortex phellodendr): 3 (Fructus Gardeniae) had the best efficacy on ischemic stroke, which could be ascribed to its modulation on AA metabolism. This integrated metabolomics approach showed the potential and applicable in deciphering the complex mechanisms of traditional Chinese medicine formulae on the treatment of complicated diseases, which provided new means to assess the treatment effects of herb combinations and to further development of drugs or therapies based on these formulae.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University Nanjing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Center for Molecular Metabolism, Nanjing University of Science and Technology Nanjing, China.
authors.forename: Junsong
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University Nanjing, China.
authors.forename: Shanting
authors.initials: S
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University Nanjing, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University Nanjing, China.
authors.forename: Dingqiao
authors.initials: D
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University Nanjing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lv
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University Nanjing, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University Nanjing, China.
authors.forename: Lingyi
authors.initials: L
authors.lastname: Kong
keywords: Huang-Lian-Jie-Du-Decoction; amino acids; correlation network; ischemic stroke; metabolomics; middle cerebral artery occlusion; orthogonal experimental design