Tetrandrine Improves Ventricular Remodeling and Inflammation via Inhibition of the MAPK/NF-κB Pathway.

BACKGROUND

Tetrandrine (TET), a bisbenzylisoquinoline alkaloid, has been shown to possess various benefits for cardiovascular diseases and anti-inflammatory activities. However, the role of TET in hypertensive heart failure is not fully known. This study was undertaken to explore whether TET exerts anti-ventricular remodeling effects and to identify the mechanisms involved.

METHODS

C57BL/6 mice were subjected to 4-week infusion of angiotensin II (Ang II) or transverse aortic constriction (TAC) surgery to induce ventricular remodeling. The mice received TET (5 mg/kg/day and 10 mg/kg/day) for the last 2 weeks.

RESULTS

We found that TET dose-dependently prevented heart malfunction due to the inhibition of myocardial hypertrophy, cardiac fibrosis, and inflammation without any effect on the systolic blood pressure in Ang II-infusion mice. TET treatment also attenuated TAC-induced myocardial hypertrophy and fibrosis in the mice. The cardioprotective effects of TET were also confirmed in H9C2 cells with Ang II stimulation. TET diminished the inflammatory response in heart tissues and cardiomyocytes by suppressing the Ang II-activated mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathway. With a combination of JNK and ERK inhibitors and TET, the anti-inflammatory effects and the inhibition of the nuclear translocation of the NF-κB p65 subunit were enhanced in Ang II-stimulated cardiomyocytes.

CONCLUSIONS

Taken together, these data strongly suggest that TET attenuated the Ang II-or TAC-induced ventricular remodeling, which was possibly associated with the inhibition of inflammation and activation of the MAPK/NF-κB pathway in mice. These findings suggest a novel pharmacological activity for TET in the treatment of heart failure.