Zhenyuan Solid Drink Ameliorates Inflammation and Oxidative Stress in Isoproterenol-Induced Ischemic Myocardial Infarction via TLR4/NF-κB Pathway and PI3K/AKT1/NRF2 Pathway in Rats.
Zhenyuan Solid Drink (ZYSD) is a formulation consisting of 6 medicinal herbs that can be used as both food and medicinal materials in China. This comprehensive analysis aims to illuminate the potential therapeutic effects and underlying mechanisms of ZYSD in the context of ischemic myocardial infarction. Marker components in ZYSD were identified by high performance liquid chromatography (HPLC) through comparison with reference compounds. Isoproterenol (ISO)-induced rats were employed as the in vivo model of ischemic myocardial infarction. Subsequently, a multi-tiered approach integrating cardiac color Doppler ultrasound, cardiac enzyme marker analysis, inflammatory factor detection, gut microbiota profiling, network pharmacology, molecular docking, molecular dynamics (MD) simulation, and western blot analysis was employed to elucidate the effects and underlying mechanisms of ZYSD, with intervention in alleviating metoprolol tartrate as positive control. Ten compounds, derived from 6 medicinal plants, in ZYSD were identified as marker components for the quality control via HPLC. Animal studies confirmed the preventive and therapeutic efficacy of ZYSD against ischemic myocardial infarction, as evidenced by the improvement of cardiac function and the attenuation of inflammation and oxidative stress. Using network pharmacology and molecular docking, the active constituents including marker compounds of ZYSD exhibited strong binding affinity to their key targets, including AKT1 and NRF2. MD simulation further indicated the binding interaction between ZYSD components and AKT1. Western blot analysis results further verified that ZYSD regulates the TLR4/NF-κB pathway and PI3K/AKT1/NRF2 pathway. Collectively, our findings demonstrate that ZYSD mitigates inflammation and oxidative stress, potentially through the TLR4/NF-κB and PI3K/AKT1/NRF2 pathways, thereby providing a novel strategy for the prevention and treatment of ischemic myocardial infarction.
