[Protective effect of silibinin against isoproterenol-induced injury to cardiac myocytes and its mechanism].
Silibinin is a polyphenolic flavanoid derived from fruits and seeds of milk thistle (Silybum marianum). To investigate the effect and mechanism of silibinin on beta-isoproterenol-induced rat neonatal cardiac myocytes injury, the viability, the activation of lactate dehydrogenase (LDH) and the content of maleic dialdehyde (MDA) were chosen for measuring the degree of cardiac myocytes injury. Superoxide dismutase (SOD) activity, mitochondrial membrane potential (deltapsi) detected by flow cytometric analysis, and Western blotting analysis were applied to determine the related proteins. Silibinin protected isoproterenol-treated rat cardiac myocytes from death and significantly decreased LDH release and MDA production. Silibinin increased superoxide dismutase (SOD) activity, and increased mitochondrial membrane potential (deltapsi). Furthermore, the release of pro-apoptotic cytochrome c from mitochondria was reduced by silibinin. Silibinin increased the expression of anti-apoptotic Bcl-2 family protein Bcl-2, and up-regulation of SIRT1 inhibited the translocation of Bax from cytoplasm to mitochondria, which caused mitochondrial dysfunction and cell injury. Silibinin protects cardiac myocytes against isoproterenol-induced injury through resuming mitochondrial function and regulating the expression of SIRT1 and Bcl-2 family members.
Zhou
Bei
B
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China.
Wu
Li-Jun
LJ
Tashiro
Shin-ichi
S
Onodera
Satoshi
S
Uchiumi
Fumiaki
F
Ikejima
Takashi
T
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007545:Isoproterenol / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D020944:Silybum marianum / Q000737:chemistry; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010946:Plants, Medicinal / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077385:Silybin; D012838:Silymarin / Q000302:isolation & purification / Q000494:pharmacology; D056564:Sirtuin 1; D037761:Sirtuins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D002316:Cardiotonic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012838:Silymarin; D051028:bcl-2-Associated X Protein; D000077385:Silybin; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D037761:Sirtuins; D007545:Isoproterenol