Effects of neutral sulfate berberine on LPS-induced cardiomyocyte TNF-α secretion, abnormal calcium cycling, and cardiac dysfunction in rats

Aim： To evaluate the effect of neutral sulfate berberine on cardiac function, tumor necrosis factor α （TNF-α） release, and intracellular calcium concentration （[Ca^2＋]i） in cardiomyocytes exposed to lipopolysaccharide （LPS）. Methods： Primary cultured rat cardiomyocytes were prepared from ventricles of 3-4-day old Sprague-Dawley rats. TNF-α concentrations in cell-conditioned media were measured by using a Quantikine enzyme-linked immunosorbent assay kit, and cardiomyocyte [Ca^2＋]i was measured by using Fura-2/AM. The isolated rat hearts were perfused in the Langendorff mode. Results： LPS at doses of 1, 5, 10, and 20 μg/mL markedly stimulated TNF-α secretion from cardiomyocytes, and neutral sulfate berberine inhibited LPS-induced TNF-α production. Intracellular calcium concentration was significantly decreased after LPS stimulation for 1 h, and increased 2 h after LPS treatment. Pretreatment with neutral sulfate berberine reversed the LPS-induced [Ca^2＋]i alterations, although neutral sulfate berberine did not inhibit a rapid increase in cardiomyocyte [Ca^2＋]i induced by LPS. Perfusion of isolated hearts with LPS （100 μg/mL） for 20 min resulted in significantly impaired cardiac performance at 120 min after LPS challenge： the maximal rate of left ventricular pressure rise and fall （±dp/dtmax） decreased compared with the control. In contrast, ±dp/dtmax at 120 min in hearts perfused with neutral sulfate berberine （1μmol/L） for 10 min followed by 20 min LPS （100 μg/mL） was greater than the corresponding value in the LPS group. Conclusion： Neutral sulfate berberine inhibits LPS-stimulated myocardial TNF-α production, impairs calcium cycling, and improves LPS-induced contractile dysfunction in intact heart.