Salacia Oblonga Root Decreases Cardiac Hypertrophy in Zucker Diabetic Fatty Rats: Inhibition of Cardiac Expression of Angiotensin II Type 1 Receptor

Aims: We investigated the effect of the water extract of Salacia oblonga (SOE), an ayurvedic antidiabetic and antiobesity medicine, on obesity and diabetes-associated cardiac hypertrophy and discuss the role of modulation of cardiac angiotensin II type 1 receptor (AT(1)) expression in the effect.

Methods: SOE (100 mg/kg) was given orally to male Zucker diabetic fatty (ZDF) rats for 7 weeks. At the end-point of the treatment, the hearts and left ventricles were weighed, cardiomyocyte cross-sectional areas were measured, and cardiac gene profiles were analysed. On the other hand, angiotensin II-stimulated embryonic rat heart-derived H9c2 cells and neonatal rat cardiac fibroblasts were pretreated with SOE and one of its prominent components mangiferin (MA), respectively. Atrial natriuretic peptide (ANP) mRNA expression and protein synthesis and [(3)H]thymidine incorporation were determined.

Results: SOE-treated ZDF rats showed less cardiac hypertrophy (decrease in weights of the hearts and left ventricles and reduced cardiomyocyte cross-sectional areas). SOE treatment suppressed cardiac overexpression of ANP, brain natriuretic peptide (BNP) and AT(1) mRNAs and AT(1) protein in ZDF rats. SOE (50-100 microg/ml) and MA (25 micromol) suppressed angiotensin II-induced ANP mRNA overexpression and protein synthesis in H9c2 cells. They also inhibited angiotensin II-stimulated [(3)H]thymidine incorporation by cardiac fibroblasts.

Conclusions: Our findings demonstrate that SOE decreases cardiac hypertrophy in ZDF rats, at least in part by inhibiting cardiac AT(1) overexpression. These studies provide insights into a potential cardioprotective role of a traditional herb, which supports further clinical evaluation in obesity and diabetes-associated cardiac hypertrophy.