Protective effect of crocin on chronic heart failure and its mechanism of action

Abstract

Purpose: To explore the mechanism of action of crocin in rat chronic heart failure (CHF). Methods: One hundred male Sprague Dawley (SD) rats were used to establish CHF rat model by the abdominal aorta constriction method. They were equally randomized into either the model control group (injected with distilled water), crocin low, medium, and high dose groups (daily administered 0.05, 0.1, and 0.75 g/kg of crocin, respectively), or positive control group (daily administration of benazepril hydrochloride), and normal control (without treatment). Parameters evaluated include heart function, inflammatory index changes, and oxidative stress damage. Results: The crocin low, medium, and high dose groups and the positive control group had significantly better cardiac function indices versus the model control group (p < 0.05). High-dose crocin resulted in significantly lower levels of inflammatory factors than a low or medium dose (p < 0.05). Rats that received a medium or high dose of crocin showed significantly increased activity of myocardial antioxidant enzymes, and reduced malondialdehyde (MDA) and reactive oxygen species (ROS) content when compared to those given low doses of crocin (p < 0.05). Protein expressions of Bax-activated caspase-3, and NF-kB decreased significantly with increase in crocin dosage. A high dose of crocin produced a significantly lower apoptotic rate of cardiomyocytes, sodium–calcium exchanger (NCX) level and higher content of sarcoplasmic reticulum calcium pump 2a (SERCA2a) compared with low- and medium-doses. Conclusion: Crocin protects myocardial tissue and enhances ventricular diastolic function of CHF rats through down-regulation of NCX expression and up-regulation of SERCA2a expression. Further studies using clinical CHF models to categorize and analyze crocin-related cellular pathways will be required.