Protective effects of baicalein on tert-butyl hydroperoxide-induced hepatic toxicity in rat hepatocytes

Institute of Medicine, Medical College, Chung Shan Medical University, Taichung, 402, Taiwan.
Journal of Biomedical Science (Impact Factor: 2.76). 02/2005; 12(2):389-97. DOI: 10.1007/s11373-005-1572-8
Source: PubMed

ABSTRACT Baicalein (BAL), a main flavonoid constituent of Scutellaria radix, was studied for its inhibitory effects on tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity and oxidative damage in primary cultures of rat hepatocytes. In a preliminary study, baicalein revealed effective antioxidant properties in a test of its capacity to quench the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH). Further investigations showed that baicalein, at the concentrations of 1, 5, and 10 microM, decreased the leakage of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) and the formation of malondialdehyde (MDA) induced by 30 min of pretreatment with t-BHP (1.5 mM) in primary cultures of rat hepatocytes. Baicalein also attenuated t-BHP-induced mitochondrial depolarization as determined by a retention test of rhodamine 123 and DNA repair synthesis as evidenced by unscheduled DNA synthesis (UDS). In addition, baicalein decreased the 8-hydroxy-2'-deoxyguanosine (8-OH-dG) content which acts as a DNA damage marker. The sum of the results suggests that the protective effect of baicalein against the cytotoxicity and genotoxicity of hepatocytes induced by t-BHP is due to its ability to quench free radicals.

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    • "Recent studies have shown that baicalein has beneficial effects in the liver. Baicalein attenuates tert-butyl hydroperoxide-induced hepatic toxicity in rat hepatocytes (Hwang et al., 2005). Baicalein inhibits hepatocellular carcinoma cells invasion and metastasis by reducing cell motility and migration (Chen et al., 2013). "
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    ABSTRACT: Liver dysfunction has been known to occur frequently in cases of sepsis. Baicalein, the main active ingredient of the Scutellaria root, exerts anti-inflammatory and anti-apoptotic properties in endotoxic shock. However, the role of baicalein in polymicrobial sepsis-induced liver injury and its regulatory mechanisms remain unclear. In this study, we aimed to investigate the protective effects of baicalein on polymicrobial sepsis-induced liver injury and to explore the possible mechanisms. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice. Mice were treated with baicalein (100mg/kg, i.p) at 1h, 6h and 12h following CLP. Baicalein significantly improved the survival of septic mice. Treatment with baicalein ameliorated the CLP-induced liver injury, as indicated by the lower serum aminotransferase levels and the fewer histopathologic abnormalities. Baicalein reduced the neutrophil infiltration and the hepatic inflammatory cytokine expression and release. It also decreased the hepatic and the serum high-mobility group box 1 and macrophage migration inhibitory factor levels in septic mice. Moreover, baicalein significantly inhibited the mitogen-activated protein kinases (MAPKs) activation and suppressed the transcriptional activity of nuclear factor-kappa B (NF-κB). In conclusion, these results suggest that baicalein treatment could protect against the sepsis-induced liver injury, and improve the survival of mice with polymicrobial sepsis. The mechanism of the protective action of baicalein seems to involve its ability to reduce inflammatory response, inhibit hepatic apoptosis, and to suppress MAPKs and NF-κB activation. Copyright © 2014. Published by Elsevier B.V.
    European Journal of Pharmacology 12/2014; 748. DOI:10.1016/j.ejphar.2014.12.014 · 2.53 Impact Factor
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    • "Baicalein (5, 6, 7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one) is one of the major flavonids with a defined chemical structure (Figure 1) in Scutellaria baicalensis that has long been widely used for thousands of years in oriental medicine. Several biological effects of baicalein such as anti-viral, anti-hepatotoxicity, anti-inflammation, and anti-tumor properties have been reported [18], [19], [20]. However, the anti-metastatic effect and related mechanism(s) in glioma cells have not previously been determined. "
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    ABSTRACT: Baicalein, one of the major flavonids in Scutellaria baicalensis, has historically been used in anti-inflammatory and anti-cancer therapies. However, the anti-metastatic effect and related mechanism(s) in glioma are still unclear. In this study, we thus utilized glioma cell lines U87MG and U251MG to explore the effect of baicalein. We found that administration of baicalein significantly inhibited migration and invasion of glioma cells. In addition, after treating with baicalein for 24 h, there was a decrease in the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 expression as well as proteinase activity in glioma cells. Conversely, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 was increased in a dose-dependent manner. Moreover, baicalein treatment significantly decreased the phosphorylated level of p38, but not ERK1/2, JNK1/2 and PI3K/Akt. Combined treatment with a p38 inhibitor (SB203580) and baicalein resulted in the synergistic reduction of MMP-2 and MMP-9 expression and then increase of TIMP-1 and TIMP-2 expression; and the invasive capabilities of U87MG cells were also inhibited. However, p38 chemical activator (anisomycin) could block these effects produced by baicalein, suggesting baicalein directly downregulate the p38 signaling pathway. In conclusion, baicalein inhibits glioma cells invasion and metastasis by reducing cell motility and migration via suppression of p38 signaling pathway, suggesting that baicalein is a potential therapeutic agent for glioma.
    PLoS ONE 02/2014; 9(2):e90318. DOI:10.1371/journal.pone.0090318 · 3.23 Impact Factor
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    • "The hepatocellular carcinoma cell lines HepG2 and SK-Hep1 were obtained from the American Tissue Culture Collection (ATCC, USA) and grown to confluence in Dulbecco's minimum essential medium (Gibco, USA) supplemented with 10% fetal bovine serum (Gibco, USA), 2 mM Glutamine, 1% non essential amino acids (NEAA) and a 1% antibiotic mixture (50 mg/mL of penicillin, 50 mg/ mL of streptomycin, and 10 mg/mL of neomycin/mL) at 37 C in a humidified atmosphere of 5% CO 2 . The primary rat hepatocytes were isolated from Wistar rats as previously described [14]. The isolated hepatocytes (viability > 90%) were prepared by liver perfusion with collagenase IV (Sigma) and separated by density centrifugation in Percoll solution (GE Healthcare Bio-Sciences AB). "
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    ABSTRACT: Previous research indicates that cantharidin, norcantharidin and their analogues exhibit anticancer activity due to their inhibition of cancer cell lines such as HL60, HT29 and L1210. The anticancer activities of cantharidin, norcantharidin and their analogues involve the suppression of serine/threonine protein phosphatases (PPs) activity. However, cantharidin is not suitable for cancer therapy because of its high cytotoxicity in vitro (IC(50) = 21 microM in primary cultured rat hepatocytes). In this study, synthetic cantharidin analogues with a structure of aminothiazole compounds 3-9 and a structure of anhydride compounds 10-12 were screened for anticancer activities and cytotoxic effects on human hepatocellular carcinoma cell (HCC) lines HepG2, Sk-Hep1, and primary cultured rat hepatocytes. Experimental results indicated that compounds 3-9 did not perform as expected with regard to anticancer activity and exhibited lower cytotoxicity. Compound 10 promoted apoptosis in HepG2 (IC(50) = 62 microM) and SK-Hep1(IC(50) = 151 microM) cell lines. Compounds 11 and 12 had anticancer potential similar to that of compound 10. After treatment with compounds 3-12, primary cultured rat hepatocytes exhibited no cytotoxicity (IC(50) > 200 microM). By investigating the structure-activity relationship (SAR) of these analogues as a whole, this study suggests that the anhydride ether oxygen such as in cantharidin, norcantharidin and compounds 10-12 may be correlated with HCC survival suppression. The results further suggest that the elimination of bridging ether oxygen on the ring, such as in compounds 10-12, can decrease cytotoxicity.
    European Journal of Medicinal Chemistry 09/2010; 45(9):3981-5. DOI:10.1016/j.ejmech.2010.05.053 · 3.45 Impact Factor
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