Baojie Zhu1, Huiting Cao2, Limin Sun3, Bo Li4, Liwei Guo5, Jinao Duan6, Huaxu Zhu7, Qichun Zhang8. 1. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: zhubaojie1991@163.com. 2. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: caohuiting125@126.com. 3. School of Traditional Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China. Electronic address: sunlimin92@163.com. 4. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: zodlee@163.com. 5. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: guoliwei815@yahoo.com.cn. 6. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: dja@njutcm.edu.cn. 7. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: zhuhx@njucm.edu.cn. 8. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: zhangqichun@njucm.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian Jie-Du decoction (HLJDD), a traditional formula of Chinese medicine constituted with Rhizoma Coptidis, RadixScutellariae, CortexPhellodendri amurensis and Fructus Gardeniae, exhibits unambiguous therapeutic effect on cerebral ischemia via multi-targets action. Further investigation, however, is still required to explore the relationship between those mechanisms and targets through system approaches. MATERIALS AND METHODS: Rats of cerebral ischemia were completed by middle cerebral artery occlusion (MCAO) with reperfusion. Following evaluation of pharmacological actions of HLJDD on MCAO rats, the plasma samples from rats of control, MCAO and HLJDD-treated MCAO groups were prepared strictly and subjected to ultra-performance liquid chromatography quadrupole time of flight mass spectrometry for metabolites analysis. The raw mass data were imported to MassLynx software for peak detection and alignment, and further introduced to EZinfo 2.0 software for orthogonal projection to latent structures analysis, principal component analysis and partial least-squares-discriminant analysis. The metabolic pathways assay of those potential biomarkers were performed with MetaboAnalyst through the online database, HMDB, Metlin, KEGG and SMPD. Those intriguing metabolic pathways were further investigated via biochemical assay. RESULTS: HLJDD ameliorated the MCAO-induce cerebral damage and blocked the severe inflammation response. There were nineteen different biomarkers identified among control, MCAO and HLJDD-treated MCAO groups. Ten metabolic pathways were proposed from these significant metabolites. Incorporation with the biochemical assay of cerebral tissue, modulation of metabolic stress, regulation glutamate/GABA-glutamine cycle and enhancement of cholinergic neurons function were explored that involved in the actions of HLJDD on cerebral ischemia. CONCLUSION: HLJDD achieves therapeutic action on cerebral ischemia via coordinating the basic pathophysiological network of metabolic stress, glutamate metabolism, and acetylcholine levels and function.
ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian Jie-Du decoction (HLJDD), a traditional formula of Chinese medicine constituted with Rhizoma Coptidis, RadixScutellariae, CortexPhellodendri amurensis and Fructus Gardeniae, exhibits unambiguous therapeutic effect on cerebral ischemia via multi-targets action. Further investigation, however, is still required to explore the relationship between those mechanisms and targets through system approaches. MATERIALS AND METHODS:Rats of cerebral ischemia were completed by middle cerebral artery occlusion (MCAO) with reperfusion. Following evaluation of pharmacological actions of HLJDD on MCAOrats, the plasma samples from rats of control, MCAO and HLJDD-treated MCAO groups were prepared strictly and subjected to ultra-performance liquid chromatography quadrupole time of flight mass spectrometry for metabolites analysis. The raw mass data were imported to MassLynx software for peak detection and alignment, and further introduced to EZinfo 2.0 software for orthogonal projection to latent structures analysis, principal component analysis and partial least-squares-discriminant analysis. The metabolic pathways assay of those potential biomarkers were performed with MetaboAnalyst through the online database, HMDB, Metlin, KEGG and SMPD. Those intriguing metabolic pathways were further investigated via biochemical assay. RESULTS: HLJDD ameliorated the MCAO-induce cerebral damage and blocked the severe inflammation response. There were nineteen different biomarkers identified among control, MCAO and HLJDD-treated MCAO groups. Ten metabolic pathways were proposed from these significant metabolites. Incorporation with the biochemical assay of cerebral tissue, modulation of metabolic stress, regulation glutamate/GABA-glutamine cycle and enhancement of cholinergic neurons function were explored that involved in the actions of HLJDD on cerebral ischemia. CONCLUSION: HLJDD achieves therapeutic action on cerebral ischemia via coordinating the basic pathophysiological network of metabolic stress, glutamate metabolism, and acetylcholine levels and function.