Aim:To evaluate the effect of neutral sulfate berberine on cardiac function,tumornecrosis factor α(TNF-α)release,and intracellular calcium concentration([Ca~(2+)]_i)in cardiomyocytes exposed to lipopolysaccharide(LPS).Methods:Primary cul-tured rat cardiomyocytes were prepared from ventricles of 3-4-day old Sprague-Dawley rats.TNF-α concentrations in cell-conditioned media were measured byusing a Quantikine enzyme-linked immunosorbent assay kit,and cardiomyocyte[Ca~(2+)]_i was measured by using Fura-2/AM.The isolated rat hearts were perfusedin the Langendorff mode.Results:LPS at doses of 1,5,i0,and 20 μg/mL markedlystimulated TNF-α secretion from cardiomyocytes,and neutral sulfate berberineinhibited LPS-induced TNF-α production.Intracellular calcium concentration wassignificantly decreased after LPS stimulation for 1 h,and increased 2 h after LPStreatment.Pretreatment with neutral sulfate berberine reversed the LPS-induced[Ca~(2+)]_i alterations,although neutral sulfate berberine did not inhibit a rapid in-crease in cardiomyocyte[Ca~(2+)]_i induced by LPS.Perfusion of isolated hearts withLPS(100 μg/mL)for 20 min resulted in significantly impaired cardiac performanceat 120 min after LPS challenge:the maximal rate of left ventricular pressure rise andfall(±dp/dt_(max)decreased compared with the control.In contrast,±dp/dt_(max) at 120min in hearts perfused with neutral sulfate berberine(1 μmol/L)for 10 min followedby 20 rain LPS(100 μg/mL)was greater than the corresponding value in the LPSgroup.Conclusion:Neutral sulfate berberine inhibits LPS-stimulated myocardialTNF-α production,impairs calcium cycling,and improves LPS-induced contrac-tile dysfunction in intact heart. 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) Primary cul-tured 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. Isolated rat hearts were perfused in the Langendorff mode. Results: LPS at doses of 1, 5, i0, and 20 μg / mL markedlystimulated TNF-α secretion from cardiomyocytes, and neutral sulfate berberineinhibited LPS-induced TNF-α production.Intracellular calcium concentration wassignificantly 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 in-crease 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 performanceat 120 min after LPS challenge: the maximal rate of left ventricular pressure rise andfall (± 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) followed by 20 min LPS (100 μg / mL) was greater than the corresponding value in the LPSgroup. Confclusion: Neutral sulfate berberine inhibits LPS-stimulated myocardial TNF-α production, impairs calcium cycling, and improves LPS-induced contrac-tile dysfunction in intact heart .