Puerarin ameliorates myocardial remodeling of spontaneously hypertensive rats through inhibiting TRPC6-CaN-NFATc3 pathway

Puerarin (Pue) has been widely used in the treatment of hypertension and cardiovascular diseases, but the basic mechanism of Pue on myocardial remodeling (MR) of hypertension is not clear. The purpose of this study was to investigate the effect and mechanism of Pue on MR and provide the basis for the clinical application. Thirty male spontaneously hypertensive rats (SHR) and six male Wistar Kyoto rats (WKY) aged 3 months were used in this study, SHR rats were randomly divided into 5 groups, Pue (40 or 80 mg/kg/d, ip) and telmisartan (TELMI) (30 mg/kg/d, ig) were administrated for 12 weeks. We used Echocardiography to detect the cardiac function. Morphology and structure of myocardium were observed. H9C2 cells were subjected to 1 mu M Ang II in vitro, 100 mu M Pue, 0.5 mu M Calmodulin-dependent calcineurin (CaN) inhibitor Cyclosporin A (CsA) and 1 mu M specific transient receptor potential channel 6 (TRPC6) inhibitor SAR7334 were used in H9C2 cells. Long-term administration of Pue could significantly improve cardiac function, improve morphology and structure of myocardium in vivo. Pue could reduce MR related proteins expression (ACTC1, TGF-(i1, CTGF, (i-MHC and BNP), attenuate ROS, restore MMP and decrease Ca2+-overload in vitro. Further study indicated that Pue could decrease TRPC6 expression and inhibit nuclear factor of activated T cells 3 (NFATc3) nuclear translocation in vitro. These results suggested that puerarin could ameliorate myocardial remodeling through inhibiting TRPC6-CaN-NFATc3 in spontaneously hypertensive rats.

Automated summary

This study found that long-term administration of puerarin can significantly improve cardiac function and myocardial morphology in spontaneously hypertensive rats. It reduces the expression of proteins related to myocardial remodeling, alleviates oxidative stress and calcium overload. Further experiments showed that puerarin improves myocardial remodeling by inhibiting the TRPC6-CaN-NFATc3 signaling pathway.