Lv Yan, Wang Junsong, Xu Dingqiao, Liao Shanting, Li Pei, Zhang Qian, Yang Minghua, Kong Lingyi
Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
Center for Molecular Metabolism, Nanjing University of Science and Technology, 200 Xiao Ling Wei Street, Nanjing 210094, PR China.
J Pharm Biomed Anal. 2017 Oct 25;145:794-804. doi: 10.1016/j.jpba.2017.07.062. Epub 2017 Aug 1.
Sepsis is a serious clinical disease with a high mortality rate all around the world. Liver organ dysfunction is an important sign for the severity and outcome of sepsis in patients. In this study, H NMR-based metabolomics approach and biochemical assays were applied to investigate the metabolic profiling for cecal ligation and puncture (CLP) induced acute liver injury, the therapeutical effect of single/combination use of Huang-Lian-Jie-Du decoction (HLJDD) and berberine, and the interaction of them. Metabolomics analysis revealed significant perturbations in livers of septic rats, which could be ameliorated by HLJDD, berberine and their combination treatment. Berberine could better rectified glycolysis and nucleic acid metabolism in the liver. HLJDD had exceptional better anti-inflammatory, antibacterial and antioxidative effects than berberine. The interaction of berberine and HLJDD could further strengthen the anti-inflammation and anti-oxidation, but with poor effect on amino acids metabolism. These findings highlighted the feasibility of the integrated NMR based metabolomics approach to understand the pathogenesis of diseases, the action mechanisms of therapy and the herb-drug interaction.
脓毒症是一种严重的临床疾病，在全球范围内死亡率很高。肝脏器官功能障碍是脓毒症患者病情严重程度和预后的重要标志。在本研究中，基于核磁共振氢谱（H NMR）的代谢组学方法和生化分析被用于研究盲肠结扎穿刺（CLP）诱导的急性肝损伤的代谢谱、黄连解毒汤（HLJDD）和小檗碱单用/联用的治疗效果以及它们之间的相互作用。代谢组学分析显示脓毒症大鼠肝脏存在显著的代谢紊乱，而HLJDD、小檗碱及其联合治疗可改善这些紊乱。小檗碱能更好地纠正肝脏中的糖酵解和核酸代谢。HLJDD的抗炎、抗菌和抗氧化作用比小檗碱更好。小檗碱与HLJDD的相互作用可进一步增强抗炎和抗氧化作用，但对氨基酸代谢的影响较差。这些发现突出了基于核磁共振的综合代谢组学方法在理解疾病发病机制、治疗作用机制和草药-药物相互作用方面的可行性。
