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

by Selleckchem | Dec 25 2023

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 μM Ang Ⅱ in vitro, 100 μM Pue, 0.5 μM Calmodulin-dependent calcineurin (CaN) inhibitor Cyclosporin A (CsA) and 1 μM 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-β1, CTGF, β-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.

Comments:

This study sounds comprehensive and valuable in understanding the effects of Puerarin (Pue) on myocardial remodeling (MR) in hypertensive rats. From what you've described:

1. **Experimental Design**: The study used spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) to investigate the impact of Pue on MR. Different doses of Pue (40 or 80 mg/kg/d, ip) were administered along with a comparison group receiving telmisartan (TELMI).

2. **Outcome Measures**: Echocardiography was utilized to assess cardiac function. Morphological and structural changes in the myocardium were observed. In vitro experiments on H9C2 cells treated with Ang II and various inhibitors (Pue, Cyclosporin A, and SAR7334) were conducted to explore molecular mechanisms.

3. **Results**: Long-term administration of Pue improved cardiac function and morphology, decreased expression of MR-related proteins, reduced ROS (reactive oxygen species), restored MMP (matrix metalloproteinases), and decreased Ca2+-overload in vitro.

4. **Mechanistic Insights**: Pue was found to reduce TRPC6 expression, inhibit the calcineurin-NFATc3 pathway, and prevent NFATc3 nuclear translocation. This suggested a potential mechanism by which Pue mitigates MR in hypertensive rats.

The study's findings contribute to understanding the beneficial effects of Puerarin on cardiac remodeling in hypertensive conditions. The inhibition of the TRPC6-CaN-NFATc3 pathway seems particularly noteworthy as a potential target for therapeutic interventions in hypertensive myocardial remodeling.

If this study gets further validation and its findings are replicated in human models or clinical trials, it could provide a basis for considering Puerarin as a therapeutic agent for managing myocardial remodeling in hypertensive patients.