Sclareol attenuates angiotensin II‐induced cardiac remodeling and inflammation via inhibiting MAPK signaling

Abstract 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 −1 ·d −1 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.