Effects of neutral sulfate berberine on LPS-induced cardiomyocyte TNF-alpha secretion, abnormal calcium cycling, and cardiac dysfunction in rats.
OBJECTIVE
To evaluate the effect of neutral sulfate berberine on cardiac function, tumor necrosis factor alpha (TNF-alpha) 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-alpha 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 microg/mL markedly stimulated TNF-alpha secretion from cardiomyocytes, and neutral sulfate berberine inhibited LPS-induced TNF-alpha 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 microg/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 micromol/L) for 10 min followed by 20 min LPS (100 microg/mL) was greater than the corresponding value in the LPS group.


CONCLUSIONS
Neutral sulfate berberine inhibits LPS-stimulated myocardial TNF-alpha production, impairs calcium cycling, and improves LPS-induced contractile dysfunction in intact heart.
Yang
Jing
J
Department of Pathophysiology, Medical College, Ji-nan University, Guangzhou 510632, China. owanghd@jnu.edu.cn
Wang
Hua-dong
HD
Lu
Da-xiang
DX
Wang
Yan-ping
YP
Qi
Ren-Bin
RB
Li
Jing
J
Li
Fei
F
Li
Chu-jie
CJ
D000818:Animals; D000831:Animals, Newborn; D001599:Berberine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006339:Heart Rate / Q000187:drug effects; D008070:Lipopolysaccharides; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D001599:Berberine; D002118:Calcium