Silibinin, derived from the milk thistle plant, Silybum marianum, has been traditionally used as an antihepatotoxic agent for the treatment of
liver disease. Our preliminary study demonstrated that
silibinin has protected rat cardiac myocytes against
beta-adrenergic agonist isoproterenol-induced injury through resuming mitochondrial function and regulating the expression of
SIRT1 and Bcl-2 family members. In this study, we investigate whether
silibinin has anti-apoptotic effect on
isoproterenol-treated rat cardiac myocytes. DNA damage, detected by the TUNEL and DNA fragmentation assay, was diminished
after treatment of
silibinin. Results of
nitrite and Western blot assays showed that the amount of NO and the expression of iNOS were decreased
after treatment with
silibinin, while the expression of
procaspase-3 and digestion of
caspase-3 substrates, the
inhibitor of caspase-activated DNase (ICAD) and
poly-(ADP-ribose) polymerase (PARP), were increased simultaneously. The DNA damage was reversed by down-regulation of p53 phosphorylation
after treatment with
silibinin. Result of flowcytometric analysis showed that the cell cycle was not affected, and the expression of cell cycle regulatory
protein p21 also had no change. Consequently,
silibinin protected cardiac myocytes against
isoproterenol-induced DNA damage through
caspase pathway and the expression of p53, but independent on regulation of cell cycle.