Integration of metabolomics and transcriptomics to reveal anti-chronic myocardial ischemia mechanism of Gualou Xiebai decoction.

ETHNOPHARMACOLOGICAL RELEVANCE:Gualou Xiebai decoction (GLXB), a well-known classic traditional Chinese medicine formula, is a recorded and proven therapy for the management of cardiac diseases. However, its pharmacological characteristics and mechanism of action are unclear. MATERIALS AND METHODS:The effects of GLXB and its mechanism of action in an isoprenaline-induced rat model of chronic myocardial ischemia (CMI) were investigated by incorporating metabonomics and transcriptomics. Meanwhile, the echocardiographic evaluation, histopathological analysis, serum biochemistry assay, TUNEL assay and western blot analysis were detected to revealed the protective effects of GLXB on CMI. RESULTS:The results of echocardiographic evaluation, histopathological analysis and serum biochemistry assay revealed that GLXB had a significantly cardioprotective performance by reversing echocardiographic abnormalities, restoring pathological disorders and converting the serum biochemistry perturbations. Further, the omics analysis indicated that many genes and metabolites were regulated after modeling and GLXB administration, and maintained the marked "high-low" or "low-high" trends. Meanwhile, the results from integrated bioinformatics analysis suggested that the interaction network mainly consisted of amino acid and organic acid metabolism. The results of TUNEL assay and western blot analysis complemented the findings of integrated analysis of metabolomics and transcriptomics. CONCLUSION:These findings suggested that GLXB has a curative effect in isoproterenol-induced CMI in rats. Integrated analysis based on transcriptomics and metabolomics studies revealed that the mechanism of GLXB in alleviating CMI was principally by the regulation of energy homeostasis and apoptosis, which was through a multi-component and multi-target treatment modality.