Bakuchiol protects against adverse cardiac remodeling after myocardial infraction

Background: Myocardial infarction (MI) is closely related to heart failure and death. Cardiac fibrosis after MI is related to profound changes in cardiac structure and geometry, leading to decreased cardiac function. Unfortunately, effective therapies to prevent excessive cardiac fibrosis and improve cardiac function are limited. Consequently, new therapeutic strategies are urgently required to protect cardiac function after MI. Bakuchiol (BAK), extracted from the plant seeds of Psoralea corylifolia, has shown protective effects against pathological cardiac hypertrophy. However, it is unclear whether BAK could improve cardiac function and reduce cardiac fibrosis after MI. Objective: To assess the reportability of bakuchiol as an alternative treatment against adverse cardiac remodeling after myocardial infarction. Methods: To address this question, a MI model was built on adult wild-type C57/BL 6N mice (male, 6-8 weeks, Zhejiang Vital River Laboratory Animal Technology Co., Ltd) by left coronary artery ligation and gavage with BAK (60 mg/kg/day) for 28 consecutive days. Chest cardiac ultrasonography was performed 7 and 28 days after MI using the Vevo 2100 system to assess ventricular shape and function in model mice. The effects of BAK on cardiac remodeling and function were assessed after MI. Effects of BAK on isoprenaline-induced cardiac fibroblast proliferation and migration were also studied. Results: After MI injury, BAK can attenuate adverse cardiac remodeling and maintain left ventricular ejection fraction and fraction shortening. Furthermore, mice treated with BAK after MI injury showed lower fibrosis and wider left ventricular thickness than those without BAK. In addition, BAK can inhibit cardiac myofibroblast differentiation after MI. After stimulation with isoprenaline, BAK inhibited cardiac fibroblast proliferation and migration. At the molecular level, extracellular signal-regulated kinase 2 (ERK2) and transforming growth factor (TGF)-beta 1 were inhibited in both MI mice and isoprenaline-stimulated cardiac fibroblasts after BAK treatment. Conclusions: Our data suggest that BAK treatment, as a novel therapeutic strategy, protects against adverse cardiac remodeling and maintains cardiac function after MI, likely via the ERK2 and TGF-beta 1 signaling pathways.