Combination of decaffeinated green coffee and decaffeinated green tea ameliorates cardiomyopathy through cardiotrophin-1-dependent expression regulation in a metabolic syndrome rat model: a proposed mechanism

Background: Cardiovascular diseases (CVD) are the primary medical manifestation of metabolic syndrome (MetS). Hypoxia is also involved in the pathogenesis of CVD. Since dietary intervention significantly improved the physiological condition in MetS, the development of functional food to complement conventional medical therapy is essential. Among several standard consumable products, decaffeinated green tea (DGT) and decaffeinated green coffee (DGC) have excellent activity in managing MetS-induced CVD. However, the mechanism underlying their protective activity is poorly understood. This study aimed to understand the cardio-protective activity of DGT, DGC, and a combination of the two (DGT + DGC) in managing MetS-induced CVD in vivo and in silico. Results: The MetS condition led to the upregulation of C ardiotrophin-1 (CT-1), Signal Transducer and Activator of Transcription 3 (STAT3), GATA binding protein 4 (GATA4), and B-type Natriuretic Peptide (BNP) beyond the levels of the normal (N) group, while administration of DGT, DGC, and DGT + DGC significantly decreased the expression of those genes compared with the levels of the N group (p < 0.05). The computational analysis showed that the protective role of DGT, DGC, and DGT + DGC might be achieved through AKT1 inhibition by several bioactive components present in DGT and DGC. The analysis also defined the improvement in cardio-protective activity by combining DGT and DGC. Conclusions: The administration of DGT, DGC, or DGT + DGC repaired cardiac dysfunction parameters through indirect regulation of the CT-1 signaling axis by inhibiting AKT1 activity.