Yang Na, Zou Chunpeng, Luo Wu, Xu Diyun, Wang Mengyang, Wang Yi, Wu Gaojun, Shan Peiren, Liang Guang
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
Department of Cardiology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
Phytother Res. 2023 Feb;37(2):578-591. doi: 10.1002/ptr.7635. Epub 2022 Sep 30.
Chronic inflammation plays an important role in hypertensive heart failure. Suppressing angiotensin II (Ang II)-induced cardiac inflammation may contribute to the treatment of hypertension-associated heart failure. Sclareol, a natural product initially isolated from the leaves and flowers of Salvia sclarea, possesses antiinflammatory and immune-regulation activity in various systems. However, its effect on Ang II-induced cardiac remodeling remains unknown. In this study, we have explored the potential effects of sclareol on Ang II-induced heart failure. In vivo experiments were conducted in mice with Ang II-pump infusion for 28 days. Sclareol administration at 5 mg·kg ·d significantly reduced the expression of myocardial injury markers. Sclareol also exerts protective effects against Ang II-induced cardiac dysfunction in mice which is associated with alleviated cardiac inflammation and fibrosis. Transcriptome analysis revealed that inhibition of the Ang II-activated mitogen-activated protein kinase (MAPK) pathway contributed to the protective effect of sclareol. Sclareol inhibits Ang II-activated MAPKs pathway to reduce inflammatory response in mouse hearts and cultured cardiomyocytes. Blockage of MAPKs in cardiomyocytes abolished the antiinflammatory effects of sclareol. In conclusion, we show that sclareol protects hearts against Ang II-induced injuries through inhibiting MAPK-mediated inflammation, indicating the potential use of sclareol in the prevention of hypertensive heart failure.
慢性炎症在高血压性心力衰竭中起重要作用。抑制血管紧张素II（Ang II）诱导的心脏炎症可能有助于治疗高血压相关的心力衰竭。香紫苏醇是一种最初从南欧丹参的叶子和花朵中分离出来的天然产物，在各种系统中具有抗炎和免疫调节活性。然而，其对Ang II诱导的心脏重塑的影响尚不清楚。在本研究中，我们探讨了香紫苏醇对Ang II诱导的心力衰竭的潜在影响。在通过Ang II泵输注28天的小鼠中进行体内实验。以5 mg·kg·d的剂量给予香紫苏醇可显著降低心肌损伤标志物的表达。香紫苏醇还对Ang II诱导的小鼠心脏功能障碍具有保护作用，这与减轻心脏炎症和纤维化有关。转录组分析表明，抑制Ang II激活的丝裂原活化蛋白激酶（MAPK）途径有助于香紫苏醇的保护作用。香紫苏醇抑制Ang II激活的MAPKs途径以减少小鼠心脏和培养的心肌细胞中的炎症反应。在心肌细胞中阻断MAPKs消除了香紫苏醇的抗炎作用。总之，我们表明香紫苏醇通过抑制MAPK介导的炎症保护心脏免受Ang II诱导的损伤，这表明香紫苏醇在预防高血压性心力衰竭方面具有潜在用途。
