Abstract
Aim:
To evaluate the effect of neutral sulfate berberine on cardiac function, tumor necrosis factor α (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/dtmax) decreased compared with the control. In contrast, ±dp/dtmax 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.
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Project supported by grants from the Science Foundation of Social Development in Guangdong Province (No 2002-254), Guangdong Natural Science Foundation (No 05103294), Guangzhou Science and Technology Foundation (No 2005J1-C0352).
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Yang, J., Wang, Hd., Lu, Dx. et al. Effects of neutral sulfate berberine on LPS-induced cardiomyocyte TNF-α secretion, abnormal calcium cycling, and cardiac dysfunction in rats. Acta Pharmacol Sin 27, 173–178 (2006). https://doi.org/10.1111/j.1745-7254.2006.00257.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00257.x
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