[show abstract][hide abstract] ABSTRACT: To observe the effect of beta2-adrenergic agonist clenbuterol on ischemia/reperfusion (I/R) injury in isolated rat hearts and hydrogen peroxide (H2O2)-induced cardiomyocyte apoptosis.
Isolated rat hearts were subjected to 30 min global ischemia and 60 min reperfusion on a Langendorff apparatus. Cardiac function was evaluated by heart rate, left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure, maximal rise rate of left ventricular pressure [+dp/dt(max)], and the coronary effluent (CF). Lactate dehydrogenase (LDH) in the coronary effluent, malondialdehyde (MDA), superoxide dismutase (SOD), and Ca2+-ATPase activity in the cardiac tissue were measured using commercial kits. The apoptotic cardiomyocyte was detected by terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling (TUNEL) assay. Bax/Bcl-2 mRNA levels and the expression of caspase-3 were detected by RT-PCR and immunoblotting, respectively. Cultured newborn rat cardiomyocytes were preincubated with clenbuterol, and oxidative stress injury was induced by H2O2. Cell viability and cardiomyocyte apoptosis were evaluated by flow cytometry (FCM).
In the isolated rat hearts after I/R injury, clenbuterol significantly improved diastolic function (LVEDP and CF) and Ca2+-ATPase activity. Treatment with clenbuterol increased SOD activity and decreased the MDA level and LDH release compared with the I/R group (P<0.05). Moreover, clenbuterol decreased apoptosis, which was associated with a reduction in TUNEL-positive cells, Bax/Bcl-2 mRNA, and caspase-3 expression. In H2O2-induced cardiomyocyte injury, clenbuterol increased cell viability and attenuated cardiomyocyte apoptosis. Pretreatment with ICI118551 (selective beta2-adrenergic antagonist) decreased these effects compared with the clenbuterol-treated group (P<0.05).
Clenbuterol ameliorated ventricular diastolic function by enhancing Ca2+-ATPase activity and reduced oxidative stress and cardiac myocyte apoptosis in an experimental rat model of myocardium I/R. It decreased cardiomyocyte apoptosis induced by H2O2 in vitro. It plays a key role in the cardiac protection against myocardium I/R injury.
[show abstract][hide abstract] ABSTRACT: The present study utilized LC-MS and HPLC approaches to characterize the metabolites of neferine in rat liver after an oral administration of 20 mg x kg(-1), and investigated the involvement of CYP450 isoforms in the metabolism of neferine by their selective inhibitors in vitro, separately. In positive ionization mode, besides neferine, four metabolites (M1-M4) were detected. M2 (the major metabolite) and M4 were identified as liensinine and isoliensinine by comparison with reference substances. Moreover, according to the analysis of metabolic rule of parent drug (neferine), M1 and M3 may be desmethylliensinine and desmethyl-isoliensinine, respectively. Furthermore, the metabolism of neferine in rat liver microsomes showed that the percentage inhibition of the major metabolism (liensinine) formation was 80.5% by quinidine (10 micromol x L(-1), selective CYP2D1 inhibitor) and 25.7% by ketoconazole (1 micromol x L(-1), selective CYP3A1 inhibitor). Neferine was mainly metabolized by CYP2D1 or CYP3A1 to liensinine, isoliensinine, desmethyl-liensinine and desmethyl-isoliensinine.
Yao xue xue bao = Acta pharmaceutica Sinica 11/2007; 42(10):1034-40.
[show abstract][hide abstract] ABSTRACT: We observed the effect of modified Wendan decoction (modified Wen-Dan-Tang) on a cellular model of Alzheimer's disease. Amyloid beta (Abeta) 25-35 segment neurotoxin was employed to induce a PC12 cellular model of Alzheimer's disease. After modified Wendan decoction was fed to rats, the serum containing medicine was prepared and changes in cell morphology observed. Cell mortality and survival rate was examined by trypan blue stain assay and MTT method and caspase-3 expression was detected by western blot, while cell apoptosis was examined by flow cytometry. Cell morphology of prepared serum group was better than that of controls, and cell survival rate in prepared serum group was higher than that in control (P < 0.01 or P < 0.05). Cell mortality, caspase-3 expression and apoptosis rate in prepared serum group were lower than that in control (P < 0.01 or P < 0.05). We conclude that Modified Wendan Decoction can attenuate the neurotoxicity of Abeta 25-35 and rescue neurons via suppressing apoptotic process.
Evidence-based Complementary and Alternative Medicine 10/2007; 6(3):325-30. · 1.72 Impact Factor