Yixintai granules enhance glucose and lipid metabolism after ischemic heart failure by regulating inflammatory factors via the LPS/TLR4/NF-κB signaling pathway

Background Ischemic heart failure (IHF) severely impacts patients’ quality of life and leads to frequent hospitalizations, increased healthcare costs, and increased mortality rates, thus posing a substantial global health challenge. Myocardial ischemia is a primary trigger of HF. Yixintai granules (YXT), a traditional Chinese medicine (TCM) formulation, have demonstrated clinical benefits in HF treatment; however, their underlying mechanisms remain unclear. Methods The components of YXT absorbed into the blood were identified using ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS). The key regulatory mechanisms underlying its therapeutic effects on HF were clarified using network pharmacology, and the binding affinity of key YXT components to proteins associated with the LPS/TLR4/NF-κB pathway was assessed through molecular docking. In vivo experiments involved the establishment of an HF rat model through the ligation of the left anterior descending coronary artery. In vitro experiments utilized an H9C2 cell injury model induced by lipopolysaccharide (LPS), which was subsequently treated with YXT-containing serum. Results UHPLC-MS/MS analysis identified 2,581 active components in the YXT and 1,055 active components in the YXT-containing serum. Network pharmacology indicated that the expression of pro-inflammatory cytokines mediated by the LPS/TLR4/NF-κB pathway and glucolipid metabolic disorders may significantly contribute to the anti-HF effects of YXT. Subsequent in vivo experiments revealed that YXT enhanced cardiac function, reduced myocardial fibrosis, and improved mitochondrial morphology in HF rats. Additionally, it lowered inflammatory cytokine levels and was associated with altered glucose and lipid metabolic profiles and inhibition of the LPS/TLR4/NF-κB signaling pathway. In vitro experiments revealed that YXT-containing serum alleviated LPS-induced H9c2 cardiac cell injury, reduced reactive oxygen species and inflammatory cytokine levels, and was associated with altered glucose and lipid metabolic profiles and inhibition of the LPS/TLR4/NF-κB signaling pathway. Conclusion YXT improved cardiac function and attenuated fibrosis and ultrastructural damage in IHF rats, with effects associated with LPS/TLR4/NF-κB signaling inhibition, reduced inflammation, and altered glucose/lipid metabolic profiles.