title: The components of Huang-Lian-Jie-Du-Decoction act synergistically to exert protective effects in a rat ischemic stroke model.
abstract: Huang-Lian-Jie-Du-Decoction (HLJDD, Oren-gedoku-to in Japanese) is commonly used in traditional Chinese medicine (TCM) to treat ischemic stroke. This study investigated the efficacy of various combinations of the major components of HLJDD, berberine (A), baicalin (B), and jasminoidin (C), on the treatment of ischemic stroke modeled by middle cerebral artery occlusion (MCAO) in rats. The effects of A, B and C individually and their combinations were investigated using proton nuclear magnetic resonance (1H NMR)-based metabolomics complemented with neurologic deficit scoring, infarct volume measurement, biochemistry, histopathology and immunohistochemistry, as well as quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Ischemic stroke produces severe oxidative stress, which induces further damage. Our results show that the ABC combination treatment increased levels of cellular antioxidants that scavenged reactive oxygen species during ischemia-reperfusion via the nuclear erythroid 2-related factor 2 (Nrf2) signaling cascade. These protective effects were not observed with the other treatments. These results suggest that a combination of component herbs in HLJDD exhibit stronger effects than the individual herbs alone. Our integrated metabolomics approach also provides a tractable, powerful tool for understanding the science behind TCM formulations.
authors: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, P.R. China.
authors: Qian
authors: Q
authors: Zhang
authors: Center for Molecular Metabolism, Nanjing University of Science and Technology, Nanjing, 210094, P.R. China.
authors: Junsong
authors: J
authors: Wang
authors: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, P.R. China.
authors: Chao
authors: C
authors: Zhang
authors: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, P.R. China.
authors: Shanting
authors: S
authors: Liao
authors: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, P.R. China.
authors: Pei
authors: P
authors: Li
authors: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, P.R. China.
authors: Dingqiao
authors: D
authors: Xu
authors: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, P.R. China.
authors: Yan
authors: Y
authors: Lv
authors: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, P.R. China.
authors: Minghua
authors: M
authors: Yang
authors: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, P.R. China.
authors: Lingyi
authors: L
authors: Kong
mesh_terms: D000818:Animals; D001599:Berberine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D039823:Iridoids / Q000494:pharmacology; D008297:Male; D055432:Metabolomics / Q000379:methods; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D010946:Plants, Medicinal; D066244:Proton Magnetic Resonance Spectroscopy; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D016166:Free Radical Scavengers; D039823:Iridoids; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; C000605453:huanglian-jie-du decoction; D001599:Berberine; C007835:geniposide; C038044:baicalin
keywords: Huang-Lian-Jie-Du-Decoction; ischemic stroke; metabolomics; middle cerebral artery occlusion; oxidative stress