Mu Yu, Geng Jing, Liu Chilu, Jiang Shuang, Han Yanxing, Jiang Jiandong, Wang Yuhong
State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Int J Mol Sci. 2025 May 19;26(10):4847. doi: 10.3390/ijms26104847.
Heart failure with preserved ejection fraction (HFpEF), marked by cardiac diastolic dysfunction, contributes to half of all heart failure cases globally and poses a significant public health challenge. Effective therapies for HFpEF are rare, largely due to its complex and heterogeneous pathophysiology, which often involves multiple comorbidities. Berberine (BBR), an isoquinoline alkaloid, has demonstrated beneficial effects on multiple metabolic and cardiovascular disorders; however, its impact on cardiac diastolic dysfunction in HFpEF remains poorly understood. In this study, we utilized a rat model of HFpEF induced by a sustained high-fat/high-sucrose (HFHS) diet to explore the impact and mechanisms of BBR on diastolic dysfunction. The results revealed that BBR administration effectively alleviated cardiac diastolic dysfunction and alleviated extracardiac comorbidities, including increased weight, impaired glucose tolerance, hypercholesterolemia and hypertension, in rats fed an HFHS diet. Furthermore, BBR mitigated myocardial inflammation, oxidative stress, microvascular endothelial dysfunction, and notably restored the disturbed NO-cGMP-PKG pathway. Additionally, BBR reduced myocardial fibrosis and inhibited the abnormally activated TGF-β/Smads signaling. Moreover, BBR attenuated the systemic inflammation and corrected immune dysregulation in an HFHS diet-fed rats. Our study suggests that BBR exhibits multi-beneficial effects in the prevention and management of HFpEF, demonstrating its potential as a holistic therapeutic candidate for HFpEF.
射血分数保留的心力衰竭（HFpEF）以心脏舒张功能障碍为特征，在全球所有心力衰竭病例中占一半，对公共卫生构成重大挑战。由于其复杂且异质性的病理生理学，通常涉及多种合并症，因此针对HFpEF的有效治疗方法很少见。小檗碱（BBR）是一种异喹啉生物碱，已被证明对多种代谢和心血管疾病具有有益作用；然而，其对HFpEF中心脏舒张功能障碍的影响仍知之甚少。在本研究中，我们利用持续高脂/高糖（HFHS）饮食诱导的HFpEF大鼠模型，探讨BBR对舒张功能障碍的影响及其机制。结果显示，给予BBR可有效减轻HFHS饮食喂养大鼠的心脏舒张功能障碍，并减轻心脏外合并症，包括体重增加、糖耐量受损、高胆固醇血症和高血压。此外，BBR减轻了心肌炎症、氧化应激、微血管内皮功能障碍，并显著恢复了紊乱的NO-cGMP-PKG途径。此外，BBR减少了心肌纤维化，并抑制了异常激活的TGF-β/Smads信号传导。此外，BBR减轻了HFHS饮食喂养大鼠的全身炎症，并纠正了免疫失调。我们的研究表明，BBR在HFpEF的预防和管理中具有多种有益作用，证明了其作为HFpEF整体治疗候选药物的潜力。
