Aim To investigate the effect of mulberry extract (ME) on inflammatory response and apoptosis of cardiomyocytes induced by lipopolysaccharide (LPS) and its molecular mechanism. Methods H9c2 cells in normal culture were cultured as control group; H9c2 cells were treated with 10 mg/L LPS as LPS group; H9c2 cells were treated with 0,0 and 200 mg/L ME, and then treated with 10 mg/L LPS, as low, medium and high concentration ME groups.After transfection of si-NC and si-S100B into H9c2 cells, the cells were treated with 10 mg/L LPS, as LPS＋si-NC group and LPS＋si-S100B group. After transfection of pcDNA and pcDNA-S100B into H9c2 cells, the cells were treated with 200 mg/L ME followed by 10 mg/L LPS, as LPS＋ME＋pcDNA group and LPS＋ME＋pcDNA-S100B group. The levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay. Flow cytometry was used to detect apoptosis; Western blot was used to detect the expressions of Bcl-2, Bax and S100 calcium binding protein B (S100B); Real-time quantitative PCR was used to detect the expression of S100B mRNA. ResultsThe levels of TNF-α and IL-6 in cardiomyocytes treated with different concentrations of ME were significantly decreased, the apoptosis rate was significantly decreased, the expression of Bcl-2 was significantly increased, the expression of Bax was significantly decreased, and the expression of S100B was significantly decreased, with concentration-dependent manner (P＜0.05). Interference of S100B expression inhibited LPS-induced inflammatory response and apoptosis of cardiomyocytes. Overexpression of S100B reversed the inhibitory effect of ME on LPS-induced inflammatory response and apoptosis of cardiomyocytes. Conclusion ME can inhibit LPS-induced inflammatory response and apoptosis of cardiomyocytes, and its mechanism may be related to the down-regulation of S100B.