Acta Pharmacologica Sinica 2006 February; 27 (2): 173-178; doi: 10.1111/j.1745-7254.2006.00257.x

Aim: To evaluate the effect of neutral sulfate berberine on cardiac function, tumor necrosis factor a (TNF-α) release, and intracellular calcium concentration ([Ca²⁺]_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 [Ca²⁺]_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 [Ca²⁺]_i alterations, although neutral sulfate berberine did not inhibit a rapid increase in cardiomyocyte [Ca²⁺]_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/dt_max) decreased compared with the control. In contrast, ±dp/dt_max at 120 min in hearts perfused with neutral sulfate berberine (1 µmol/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.

Keywords: lipopolysaccharide; berberine; cardiomyo-cytes; tumor necrosis factor; intracellular calcium; heart dysfunction