ETHNOPHARMACOLOGICAL RELEVANCE: Sleep deprivation (SD) has become a major public health concern in modern society and is closely associated with an increased risk of myocardial injury. However, current therapeutic strategies are often limited by high costs and notable adverse effects. Anmei Decoction (AMD), a classical traditional Chinese medicine formula, has shown promising clinical efficacy in alleviating SD-induced myocardial injury, yet the underlying mechanisms of its cardioprotective effects remain to be fully elucidated.
OBJECTIVE: This study aims to systematically elucidate the underlying mechanisms by which AMD alleviates SD-induced myocardial injury through integrating behavioral tests, morphological assessments, multi-omics analysis, and molecular biology techniques.
METHODS: In this study, UPLC-MS/MS is employed for the analysis of the effective components and quantitative profiling of AMD. An in vivo SD rat model is established using a modified multi-platform aquatic environment method. Electrocardiography, echocardiography, and myocardial pathological staining are utilized to assess the extent of myocardial injury. To investigate the underlying mechanisms, transcriptomics, proteomics, immunofluorescence, real-time quantitative PCR (RT-QPCR,), and Western blotting (WB) are applied for comprehensive evaluation.
RESULTS: Thirty-six components of the AMD extract were quantified using UPLC-MS/MS. AMD significantly improved impaired myocardial function by reducing HW/BW ratios, restoring normal ECG rhythms, and normalizing EF, LVFS, LVEDs, and LVEDd values. It markedly reversed myocardial pathological damage by attenuating fibrosis and collagen deposition, reducing cell apoptosis and hypertrophy, and modulating mitophagy. Transcriptomic and proteomic analyses revealed that AMD alleviates myocardial injury by regulating autophagy, apoptosis, and mitophagy via the PI3K-Akt, mTOR, and HIF-1 signaling pathways. Specifically, AMD treatment significantly upregulated PI3K, Akt, mTOR, and p62 protein and mRNA levels, while downregulating HIF-1α, LC3, BNIP3, and Beclin-1, indicating that AMD mitigates myocardial injury by modulating mitophagy through the PI3K/Akt/mTOR/HIF-1 pathway.
CONCLUSION: This study demonstrates that AMD alleviates SD-induced myocardial fibrosis, hypertrophy, and apoptosis by modulating mitophagy via the PI3K/Akt/mTOR/HIF-1 signaling cascade, thereby improving myocardial functional impairment.
