Integrated metabolomics and gut microbiome to the effects and mechanisms of naoxintong capsule on type 2 diabetes in rats

Naoxintong Capsule (NXT) is a Traditional Chinese Medicine formulation which has been widely applied in treating cardiovascular and cerebrovascular diseases. Previous studies also reported the potential effects of NXT against diabetes and certain complications, yet its mechanisms remain largely obscured. Herein, in this study, we investigated the anti-diabetic effects of NXT as well as its potential mechanisms. Type 2 diabetes (T2D) was induced in rats by 10-week high-fat diet in companion with a low-dose streptozotocin injection. NXT was administrated for additional 8 weeks. The results showed that NXT exerted potent efficacy against T2D by alleviating hyperglycemia and hyperlipidemia, ameliorating insulin resistance, mitigating inflammation, relieving hypertension, and reducing myocardial injuries. To investigate its mechanisms, by integrating sequencing of gut microbiota and serum untargeted metabolomics, we showed that NXT could significantly recover the disturbances of gut microbiota and metabolic phenotypes in T2D rats. Several feature pathways, such as arachidonic acid metabolism, fatty acid β-oxidation and glycerophospholipid metabolism, were identified as the potential mechanisms of NXT in vivo. In summary, our study has comprehensively revealed the anti-diabetic effects of NXT which could be considered as a promising strategy for treating metabolic disorders, T2D and diabetic related complications in clinical practice.