European Journal of Pharmacology

Questions: 1. In few sentence write the major conclusion of the experiments presented in figure 2?2. what is /are the potential biological impacts of the result in these manuscripts? justify your response/s?3. what did you find the most challenging or interesting in these papers? Answers: 1. Silymarin block cell cycle cascade in eukaryotic cells. Cyclin dependent kinase inhibitors (CDK-I) are used to arrest cell cycle progression. CDKI are of various types such as CDK-2, CDK-1, CDK-4/6. In this immunoprecipitation and western blotting techniques were used. Time dependent studies are conducted in this experiment. Silymarin showed inhibition of erbB1 and activation of SHC gene, which are associated with the alteration in cell cycle. Fig 2 showed a significant increase in protein level related to CDKI. Maximum up- regulation occur in fig. 2A and 2B at 24 hrs and after that there was no rise in protein level. In Fig. 2C 2E, no change in the protein levels of CDK2CDK6 at 75 g/ml for 48 hrs. There was no alteration in expression of cyclin E D1 up to 48 hrs at 75 g/ml, as they form complex with CDK in the cell cycle. Therefore cyclin are not supressed by silymarin. 2. In paper 6, silymarin decrease activity of cyclin D1 (responsible for activation of cyclin dependent kinase in cell cycle cascade) and degradation of cyclin D1 by threonine-286 phosphorylation. Silymarin showed inhibitory effect on proliferation of human colon cancer cell growth by 11%, 22% and 48% at conc. 50, 100 and 200 M. silymarin attenuated BAY11-7081 cancer cell line by 2.8 folds through activation of NF-KB inhibitor. In paper 4, silymarin act as potent drug in treatment of liver disease and primary liver cancer. It suppresses activation of tumor necrosis factor alpha, by decrease proliferation, angiogenesis and insulin resistance. Silymarin was given to 36 patients for 6 months and beneficial effect shown to increase in immune response of the body, serum fibrogen decreased and decreased in fibrogenesis. In paper 5, silymarin effectively reduced platelet activation and FeCl3 induced thrombosis. SYM at 100 and 300mg/Kg reduced expression of PGC-1/, FOXO1 and PPAR. 3. Interesting facts in these papers are Silymarin (SYM) found to be a potent drug in human colon cancer by augmented cyclin D1 in cell cycle cascade. It can reduce BAY11-7081 colon cancer cell growth by 2.8 folds by decreasing proliferation, angiogenesis and activation of NF-KB inhibitors. SYM found to be effective in the treatment of liver diseases and cancer related to the liver. Various clinical trials were performed which showed that SYM decrease tumor activation factor. SYM worked as an activator of CDKI to significantly increase in protein levels.