A Metabonomics Investigation into the Therapeutic Effects of BuChang NaoXinTong Capsules on Reversing the Amino Acid-Protein Interaction Network of Cerebral Ischemia

Oxidative Medicine and Cellular Longevity - Tập 2019 - Trang 1-14 - 2019
Jing Xu1, Xin Liu2, Liyu Luo3, Liying Tang1, Na Guo4, Mengting Liu1, Hongmei Li1, Fangbo Zhang1, Yi Zhang1, Defeng Li1, Ye Zhao1, Hongwei Wu1, Hongjun Yang1
1Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
2School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China
3School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China
4Experimental Research Centre, China Academy of Chinese Medical Sciences, Beijing 100700, China

Tóm tắt

Background. Amino acids (AAs) in cerebrospinal fluid (CSF) play a pivotal role in cerebral ischemia (CI). BuChang NaoXinTong Capsules (BNC) are widely prescribed in Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases. Methods. In order to investigate the therapeutic effects and pharmacological mechanisms of BNC on reversing CI from a system level, an amino acid-protein interaction imbalanced network of CI containing metabolites of AAs, key regulatory enzymes, and proteins was constructed for the first time. Furthermore, a novel method for detecting the ten AAs in CSF was developed by UPLC-QQQ-MS in an effort to validate the imbalanced networks and the therapeutic effects of BNC via analysis of metabolites. Results. Based on a middle cerebral artery occlusion (MCAO) rat model, the dynamic levels of amino acids in CSF 3, 6, 12, and 24 h after MCAO were analyzed. Up to 24 h, the accumulated nine AA biomarkers were found to significantly change in the MCAO group compared to the sham group and exhibited an obvious tendency for returning to baseline values after BNC treatment. In addition, based on the imbalanced network of CI, four key enzymes that regulate the generation of BNC-mediated AA biomarkers were selected and validated using an enzyme-linked immunosorbent assay and western blotting. Finally, aromatic-L-amino-acid decarboxylase (AADC) was found to be one of the putative targets for BNC-mediated protection against CI. Conclusion. This study provides new strategies to explore the mechanism of cerebral ischemia and help discover the potential mechanism of BNC.

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Oxidative Medicine and Cellular Longevity

Tập 2019

1-14

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