Carnosic acid and Rosmarinic acid are family of polyphenols that are found in Rosmary plant. They have property biological behaviors such as anti-cancer, anti-viral and anti-oxidants. This study compared the effects of these two compounds based on ceramide metabolism in cell line of Hep- G2. In this experimental study, Hep-G2 cells were cultured in DMEM supplemented containing bovine fetal serum and antibiotics. Cells with double dilution were then cultured from  tow substance Carnosic acid and Rosmarinic acid from concentrations  0 to 70 µM for 24 h and viability of cells was determined by MTT method.  Spectrophotometer was used to measure of caspase-3 activity.To measure the level of ceramide, a recombinant ceramidase acid enzyme and naphthalene-2,3-dialdehyde, which is fluorescent and is connected to sphingosine resulted from ceramidase acid, were added to the cell extract and was ultimately determined by HPLC. In this study also activity of ensymes as sphingomylinase, acid ceramidase, glucosyl ceramide synthase was measured. Carnosic acid increased cell viability dose-dependent in Hep-G2 cells by reducing ceramide levels and decreasing activity of ensymes as caspse-3, sphingomylinase, glucosyl ceramide synthase and  increasing activity of the enzyme acid ceramidase. Rosmarinic acid in concentrations of up to 50 µM decreased cell viability by increasing ceramide levels and activity of caspse-3, sphingomylinase and decreasing activity of  enzymes as acid ceramidese and glucosyl ceramide synthase. Also this substance in concentrations of up to 40 µM caused increasing activity of caspse-3 enzyme. Although in most cases, polyphenols have resulted in induction of apoptosis and decreased cell viability, but in some cases they have inversely affected and caused cell growth.

Catechin, epicatechin gallate (ECG) and quercetin, as bioactive flavonoids, have been shown to possess anticarcinogenic effects. Ceramide plays an important role in killing tumor cells. Accordingly, the aim of this study was to clarify the involvement of these compounds in ceramide metabolism in A549 cancerous cell line. Spectrophotometer, cell culture and HPLC methods were used. Cell viability index showed different potential of cytotoxicity effect for each of the studied agents, among which ECG was more potent. This index decreased significantly over 100 to 250 µM concentrations of treatment with respect to control. Cell treatments also caused considerable increase in ceramide level within cells in a dose-dependent manner. Sphingomyelinase activity increased significantly in treatment with quercetin and catechin. There was significant inhibition in acid ceramidase activity of cell extract in response to each of the three compounds, particularly over 100 µM in comparison with control. Data also showed no significant variation in glycosyl ceramide synthase activity in treated cells with quercetin, whereas the activity decreased significantly by Catechin and/or ECG. It is our conviction that different effects on ceramide metabolism enzymes may be related to various chemical groups on the common structure of the studied compounds. Due to structure-function relationship, these compounds had different effects on ceramide generation. Elevation in ceramide content in A549 cancer cell line induced apoptosis, which led to anti-cancerous effects, as observed in this study.