Research Papers:

The components of Huang-Lian-Jie-Du-Decoction act synergistically to exert protective effects in a rat ischemic stroke model

Qian Zhang, Junsong Wang, Chao Zhang, Shanting Liao, Pei Li, Dingqiao Xu, Yan Lv, Minghua Yang and Lingyi Kong _

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Oncotarget. 2016; 7:80872-80887. https://doi.org/10.18632/oncotarget.12645

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Qian Zhang1, Junsong Wang2, Chao Zhang1, Shanting Liao1, Pei Li1, Dingqiao Xu1, Yan Lv1, Minghua Yang1, Lingyi Kong1

1State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, P.R. China

2Center for Molecular Metabolism, Nanjing University of Science and Technology, Nanjing, 210094, P.R. China

Correspondence to:

Lingyi Kong, email: [email protected]

Junsong Wang, email: [email protected]

Keywords: ischemic stroke, metabolomics, Huang-Lian-Jie-Du-Decoction, middle cerebral artery occlusion, oxidative stress

Received: June 29, 2016    Accepted: September 28, 2016    Published: October 13, 2016


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.

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