Metabolomics coupled with integrative pharmacology reveal the protective effect of FangjiHuangqi Decoction against adriamycin-induced rat nephropathy model

Abstract

With the development of the society, the number of people who got the nephrotic syndrome (NS) is going up roughly. Therefore, finding a better way to treat NS is becoming a major global public health issue. As we all know, traditional Chinese medicine (TCM), especially Fangji Huangqi Decoction (FHD), has a long history and has good curative effects on NS. However, the mechanism of FHD treating NS has not been clearly elucidated. To address this problem, a feasible system was developed by metabolomics and integrative pharmacology approach. To study the mechanisms of Chinese medical formula FHD treating NS based on metabolomics and integrative pharmacology. In this study, a NMR based metabolomics approach coupled with biochemical assay and Western Blot had been employed to study the protective effect of FHD against adriamycin-induced nephropathy using rat model. And we proposed a integrative pharmacology-based method, which combined chemical ingredients database building, target identification and network analysis. These were aimed to decipher the mechanisms of action for the FHD in NS treatment. Multivariate analysis revealed that 13 of 16 perturbed metabolites could be reversed by FHD, and the MetaboAnalyst analysis revealed that the anti-nephrotic syndrome effect of FHD was probably related with regulation of alanine, aspartate and glutamate metabolism, citrate cycle, pyruvate metabolism, cysteine and methionine metabolism and glyoxylate and dicarboxylate metabolism. The integrative pharmacology analysis revealed 93 potential targets for FHD, and suggested that the protective effect of FHD on the nephrotic syndrome was probably related with the regulation of immune, and energy metabolic and fatty acid metabolic. In addition, both the metabolomics and the integrative pharmacology are focus together on the alanine, aspartate and glutamate metabolism pathway. These metabolites changes and the core targets changes, as well as the metabolite-target pathway network provide insights into the mechanisms of FHD treating nephrotic syndrome, and further studies are needed to validate the bioactive compounds responsible for the anti-nephrotic syndrome effect of FHD.