Author + information
- Feng Hong,
- Jianglei Cao,
- Guangyu Zhang and
- Hong Feng
Kaempherol has been demonstrated to provide benefits for the treatment of atherosclerosis, coronary heart disease, hyperglycemia and diabetes through its antioxidant and anti-inflammatory properties. However, its role in cardiac hypertrophy remains unclear. Here, we conducted a series of experiments in vivo and in vitro to investigate its role in cardiac hypertrophy and elucidate the underlying mechanism.
Male C57BL/6J mice were subjected to thoracic aorta constriction (TAC) to induce the model of cardiac hypertrophy in vivo. After 1 week of surgery, the TAC and normal control mice were treated with or without kaempherol (100mg/kg, qd, po) in the following 8 weeks. The echocardiography and pressure-volume loops were performed to evaluate the cardiac function. Hematoxylin and eosin (HE) and Sirius Red in saturated picric acid solution (PSR) staining were used to detect the cardiomyocytes area and pathological changes. The expression levels of related mRNAs and proteins were assayed by reverse transcription PCR and Western-blot respectively. Besides, H9c2 cardiomyocytes were treated with or without phenylephrine (PE) (50uM) and kaempherol (25uM) for further investigation in vitro. The commercial kits were used to detect the oxidative stress level both in vivo and in vitro experiments.
Treatment with kaempherol significantly attenuated cardiac hypertrophy evidenced by decreased cardiomyocytes areas, heart weight/body weight, lung weight/body weight ratios and interstitial fibrosis, accompanied with the improvement of systolic and diastolic functions. The MAPK signaling pathways (ERK1/2, JNK1/2 and p38) were markedly activated in the mice subjected to TAC and H9c2 cardiomyocytes treated with PE (50uM). However, treatment with kaempherol significantly blunted the activity of JNK1/2 and p38 but had no obviously effect on ERK1/2. Furthermore, we also demonstrated that kaempherol could prevent the heart from pathological oxidative stress both in vitro and in vivo.
Our investigation indicated that treatment of Kaempferol could retard theprocess of cardiac hypertrophy induced by pressure overload both in vivo and in vitro. The underlying mechanism may be partly involved in the inhibiting of MAPK signaling pathway and the regulation of oxidative stress.