Cardiac metabolic remodeling is recognized as an important hallmark of heart failure (HF), while strategies that target energy metabolism have therapeutic potential in treating HF. Shen-Fu formula (S-F) is a standardized herbal preparation frequently used in clinical practice and is a promising combinatorial therapy for HF-related metabolic remodeling. Herein, we performed an untargeted multi-omics analysis using transcriptomics, proteomics, and metabolomics on HF mice induced by transverse aortic constriction (TAC). Integrated and pathway-driven analyses were used to reveal the therapeutic targets associated with S-F treatment. The cardioprotective effect and potential mechanism of S-F were verified by the results from echocardiography, hemodynamics, histopathology, and biochemical assays. As a result, S-F significantly alleviated myocardial fibrosis and hypertrophy, thus reducing the loss of heart function during adverse cardiac remodeling in TAC mice. Integrated omics analysis showed that S-F synergistically mediated the metabolic flexibility of fatty acids and glucose in cardiac energy metabolism. These effects of S-F were confirmed by the activation of AMP-activated protein kinase (AMPK) and its downstream targets in the failing heart. Collectively, our results demonstrated that S-F suppressed cardiac metabolic remodeling through activating AMPK-related pathways via energy-dependent mechanisms.

中文翻译：

---

通过联合治疗调节能量代谢减弱心力衰竭中的心脏代谢重塑

心脏代谢重塑被认为是心力衰竭 (HF) 的重要标志，而针对能量代谢的策略在治疗 HF 方面具有治疗潜力。参复方 (SF) 是临床实践中经常使用的标准化草药制剂，是一种很有前景的 HF 相关代谢重塑组合疗法。在此，我们使用转录组学、蛋白质组学和代谢组学对横向主动脉缩窄 (TAC) 诱导的 HF 小鼠进行了非靶向多组学分析。综合和通路驱动的分析用于揭示与 SF 治疗相关的治疗靶点。超声心动图、血流动力学、组织病理学和生化分析的结果证实了 SF 的心脏保护作用和潜在机制。其结果，SF 显着减轻了心肌纤维化和肥大，从而减少了 TAC 小鼠心脏重构过程中心脏功能的丧失。综合组学分析表明，SF协同介导脂肪酸和葡萄糖在心脏能量代谢中的代谢灵活性。SF 的这些作用通过 AMP 活化蛋白激酶 (AMPK) 及其在衰竭心脏中的下游靶标的激活得到证实。总的来说，我们的结果表明，SF 通过能量依赖机制激活 AMPK 相关通路来抑制心脏代谢重塑。综合组学分析表明，SF协同介导脂肪酸和葡萄糖在心脏能量代谢中的代谢灵活性。SF 的这些作用通过 AMP 活化蛋白激酶 (AMPK) 及其在衰竭心脏中的下游靶标的激活得到证实。总的来说，我们的结果表明，SF 通过能量依赖机制激活 AMPK 相关通路来抑制心脏代谢重塑。综合组学分析表明，SF协同介导脂肪酸和葡萄糖在心脏能量代谢中的代谢灵活性。SF 的这些作用通过 AMP 活化蛋白激酶 (AMPK) 及其在衰竭心脏中的下游靶标的激活得到证实。总的来说，我们的结果表明，SF 通过能量依赖机制激活 AMPK 相关通路来抑制心脏代谢重塑。