Andrographolide Mitigates DOCA-Salt-Induced Cardiac Hypertrophy by Regulating Calcium-Handling Genes.

BACKGROUND AND

OBJECTIVES

Cardiac hypertrophy is a maladaptive response to chronic hypertension and is often associated with impaired calcium handling. Andrographolide, a bioactive diterpenoid, has shown cardioprotective effects in several preclinical models, but its role in pressure-overload-induced hypertrophy remains unclear. This study evaluated the effects of andrographolide on cardiac hypertrophy, calcium-handling gene expression, and plasma B-type natriuretic peptide (BNP) levels in a deoxycorticosterone acetate (DOCA)-salt rat model of hypertension.

MATERIALS AND

METHODS

Fifteen male Sprague-Dawley rats underwent unilateral nephrectomy followed one week later by DOCA administration (20 mg/kg, subcutaneous, twice weekly) and 1% NaCl drinking water. After two weeks of DOCA-salt exposure, rats were randomized to receive oral andrographolide (30 mg/kg/day in 0.5% carboxymethyl cellulose) or no treatment. Blood pressure was measured at weeks 2 and 5 using a tail-cuff system. At week 5, echocardiography was performed, followed by euthanasia and collection of cardiac tissue and plasma. BNP and cardiac calcium levels were measured by enzyme-linked immunosorbent assay and colorimetric assay, respectively. Sarco/endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) and ryanodine receptor (RyR) mRNA expression were quantified by PCR using β-actin as the reference gene.

RESULTS

DOCA-salt treatment significantly increased blood pressure, left ventricular hypertrophy indices, plasma BNP, and cardiac calcium levels. Andrographolide attenuated these changes and restored SERCA2a and RyR expression.

CONCLUSION

Andrographolide alleviates DOCA-salt-induced cardiac hypertrophy, likely by restoring calcium-handling pathways, supporting its therapeutic potential in hypertension-induced cardiac remodeling.