- Title
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Baicalein protects against heart failure by improving mitochondrial dysfunction and regulating endoplasmic reticulum stress to reduce apoptosis in vitro and in vivo
- Authors
- Zhang, Z., Zhang, X., Yang, Y., Wang, H., Yang, X., Xuan, L., Yang, D., Zhang, G., Wang, Y.
- Source
- Full text @ Int J Immunopathol Pharmacol
Baicalein has no acute-toxicity and cardio-toxicity to zebrafish and HL-1 cells. (a) The chemical structure of baicalein. (b) The toxicity of baicalein on HL-1 cells was measured by MTT. Zebrafish embryos were treated with different concentrations baicalein for different times. The mortalities (c) of embryo-larva were measured. (d) Teratogenic effects on zebrafish embryos and pericardial edema in 50?µmol/L baicalein. Results were presented as mean?±?SD (n???3). ###p?0.001, versus CON, *p?0.05, **p?0.01, ***p?0.001 versus ISO. |
Apoptosis of HL-1 cells upon ISO stimulation, a protective effect exerted by baicalein. (a) The effect of baicalein on the viability of HL-1 cardiomyocytes was measured via MTT assay. (b?e) The protein levels of Caspase3, Caspase9, and Cleaved-PARP in HL-1 cells were determined by western-blot. Outcomes are displayed as average ±SD (n???3). ###p?0.001, versus CON, *p?0.05, **p?0.01, ***p?0.001 versus ISO. |
Baicalein alleviated oxidative stress in HL-1 cell. (a) ROS expression in HL-1 cells was analyzed by fluorescent staining. (scale bars, 100??m; n???3 in each group). 12.5, 25, and 50?µmol/L baicalein have differences compared with ISO group. (b?d) Expression of biomarkers MDA, GSH, SOD of oxidative stress was detected by ELISA. ##p?0.01, versus CON, *p?0.05, **p?0.01, versus ISO. |
Western-blot expression of mtTFA (a, c), OPA1 (a, d), Drp1 (b, e), and MFF (b, f) was appraised in HL-1 cells treated by indicated concentration of baicalein or met within/without ISO. Results were presented as mean ±SD (n???3). ##p?0.01, ###p?0.001, versus CON, *p?0.05, **p?0.01, ***p?0.001 versus ISO. |
The expression of GRP78 (a, b), p-PERK (a, c) ATF4 (a, d) and CHOP (a, e) was analyzed in HL-1 cells by western blotting. Results were presented as mean ±SD (n???3). ##p?0.01, ###p?0.001, versus CON, *p?0.05, **p?0.01, ***p?0.001 versus ISO. |
Baicalein inhibits the effect of ISO on cardiac dysfunction in vivo. (a) Representative echocardiographic images of the left ventricle showing ventricular dilation and cardiac dysfunction in heart failure mice, while baicalein inhibited ventricular dilation and cardiac dysfunction. In the ISO group, ejection fraction (b) and shortening fraction (c) decreased significantly, after baicalein intervention, cardiac function increased. Results were presented as mean ±SD (n???3). ###p?0.001, versus CON, *p?0.05, **p?0.01, versus ISO. (d) HE staining in mouse hearts at day 28 in the different group (scale bars, 50??m; n???3 in each group). (e) Masson staining of fibrosis and area quantitation in mouse hearts at day 28 in the different group (scale bars, 50??m; n???3 in each group). |
Baicalein inhibits the effect of ISO on apoptosis and oxidative stress in vivo. (a?b) The quantification of TUNEL-positive cell number per high-power field (scale bars, 50??m; n???3 in each group). #p?0.05, versus CON, *p?0.05, **p?0.01 versus ISO. n???3. The protein levels of Caspase3 (c, d), Caspase9 (c, e), Cleaved-PARP (c, f) in cardiac of mice were determined by Western-blot. Outcomes are displayed as average ±SD (n???3). ##p?0.01, versus CON, *p?0.05, **p?0.01, ***p?0.001 versus ISO. n???3. The expression of MDA (g), GSH (h) and SOD (i) during oxidative stress in the mouse serum was determined by ELISA (n???3). #p?0.05, ##p?0.01, ###p?0.001, versus CON, *p?0.05, **p?0.01, versus ISO. |
Baicalein inhibits the expression of mitochondrial fusion/fission related protein and ER stress related protein. Western-blot expression of Drp1 (a, c), MFF (a, d), mtTFA (b, e), and OPA1 (b, f) was appraised in rat cardiacs (n???3). ##p?0.01, ###p?0.001, versus CON, *p?0.05, **p?0.01 versus ISO. Western blot expression of GRP78 (g, h), p-PERK (g, i), ATF4 (g, j), and CHOP (g, k) was analyzed in cardiac of rats (n???3). ##p?0.01, ###p?0.001, versus CON, *p?0.05, **p?0.01, ***p?0.001 versus ISO. |