Zuogui Jiangtang Shuxin formula Ameliorates diabetic cardiomyopathy mice via modulating gut-heart axis

BACKGROUND: There is growing evidence demonstrating that the gut microbiota plays a crucial role in multiple endocrine disorders, including diabetic cardiomyopathy (DCM). Research shows that the Chinese herb reduces disease occurrence by regulating gut microbiota. Zuogui Jiangtang Shuxin formula (ZGJTSXF), a Chinese medicinal formula, has been clinically used for treatment of DCM for many years. However, there is still no clear understanding of how ZGJTSXF treatment contributes to the prevention and treatment of DCM through its interaction with gut microbiota and metabolism. METHODS: In this study, mice models of DCM were established, and ZGJTSXF’s therapeutic effects were assessed. Specifically, serum glycolipid, echocardiography, histological staining, myocardial apoptosis rate were assessed. Using 16s rRNA sequencing and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), we determined the impact of ZGJTSXF on the structure of gut microbiota and content of its metabolite TMAO. The mechanism of ZGJTSXF action on DCM was analyzed using quantitative real-time PCR and western blots. RESULTS: We found that ZGJTSXF significantly ameliorated DCM mice by modulating gut-heart axis: ZGJTSXF administration improved glycolipid levels, heart function, cardiac morphological changes, inhibited cardiomyocytes apoptosis, and regulate the gut microbiota in DCM mice. Specifically, ZGJTSXF treatment reverse the significant changes in the abundance of certain genera closely related to DCM phenotype, including Lactobacillus, Alloprevotella and Alistipes. Furthermore, ZGJTSXF alleviated DCM in mice by blunting TMAO/PERK/FoxO1 signaling pathway genes and proteins. CONCLUSION: ZGJTSXF administration could ameliorate DCM mice by remodeling gut microbiota structure, reducing serum TMAO generation and suppressing TMAO/PERK/FoxO1 signaling pathway.