Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating Nrf2 antioxidative pathway: The involvement of ERK1/2 and PKC.


:Acetaminophen (APAP)-induced hepatotoxicity is the main cause of drug-induced liver injury. This study investigated the protection of baicalin and its aglycone baicalein against APAP-induced hepatotoxicity and its mechanism. Baicalein and baicalin alleviated APAP-induced hepatotoxicity both in vitro and in vivo. Moreover, this baicalin-provided protection was not diminished in hepatocytes or mice treated with β-glucuronidase inhibitor. Results of liver glutathione (GSH) and reactive oxygen species (ROS) formation demonstrated the alleviation of baicalein and baicalin on APAP-induced liver oxidative stress injury. Baicalein and baicalin induced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the expression of its downstream antioxidant genes. Baicalein and baicalin-provided protection was diminished after the application of Nrf2 siRNA in hepatocytes and Nrf2 knock-out mice. Molecular docking results indicate the potential interaction of baicalein and baicalin with kelch-like ECH-associated protein-1 (Keap1). Baicalein and baicalin induced the sustained phosphorylation of extracellular regulated protein kinases (ERK)1/2 and protein kinase C (PKC). Moreover, ERK1/2 and PKC inhibitors both abrogated Nrf2 phosphorylation and its subsequent activation, and the protection against APAP-induced hepatotoxicity induced by baicalein and baicalin. In summary, baicalein and baicalin alleviate APAP-induced hepatotoxicity by activating Nrf2 via blocking the binding of Nrf2 with Keap1 and inducing Nrf2 phosphorylation. ERK1/2 and PKC are both critical for regulating the phosphorylation of Nrf2 induced by baicalein or baicalin.


Biochem Pharmacol


Biochemical pharmacology


Shi L,Hao Z,Zhang S,Wei M,Lu B,Wang Z,Ji L




Has Abstract


2018-04-01 00:00:00












  • The morphogenetically active polymer, inorganic polyphosphate complexed with GdCl3, as an inducer of hydroxyapatite formation in vitro.

    abstract::Inorganic polyphosphate (polyP) is a physiological polymer composed of tens to hundreds of phosphate units linked together via phosphoanhydride bonds. Here we compared the biological activity of polyP (chain length of 40 phosphate units), complexed with Gd(3+) (polyP·Gd), with the one caused by polyP (as calcium salt)...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Wang X,Huang J,Wang K,Neufurth M,Schröder HC,Wang S,Müller WEG

    更新日期:2016-02-15 00:00:00

  • Ursolic acid promotes the release of macrophage migration inhibitory factor via ERK2 activation in resting mouse macrophages.

    abstract::Macrophage migration inhibitory factor (MIF) plays some pivotal roles in innate immunity and inflammation. Ursolic acid (UA), an anti-inflammatory triterpene carboxylic acid, was recently reported to induce the release of pro-inflammatory mediators in resting macrophages (Mvarphi). We investigated the effects of UA on...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ikeda Y,Murakami A,Ohigashi H

    更新日期:2005-11-15 00:00:00

  • Expression of drug resistance-associated mdr-1, GST pi, and topoisomerase II genes during cell cycle traverse.

    abstract::The expression of drug resistance-associated mdr-1, GST pi, and topoisomerase II genes was analyzed in cell cycle phase enriched populations of doxorubicin-resistant murine leukemic P388/R-84 cells. Flow cytometric analysis of bromodeoxyuridine (BrdU) incorporation and staining with anti-BrdU antibodies was used to co...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ramachandran C,Mead D,Wellham LL,Sauerteig A,Krishan A

    更新日期:1995-02-14 00:00:00

  • Benzylamine metabolism at low O2 concentrations. Relative sensitivities of monoamine oxidase, aldehyde dehydrogenase and hippurate synthesis to hypoxia.

    abstract::The O2 dependence of the metabolism of benzylamine to benzaldehyde, benzoate and hippurate was studied in isolated rat hepatocytes. The initial oxidation to benzaldehyde, catalyzed by monoamine oxidase, had an apparent Kmo2 value of 34 microM in cells and 40 microM in isolated rat liver mitochondria. The conversion of...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Jones DP

    更新日期:1984-02-01 00:00:00

  • Prenylated quinolinecarboxylic acid derivative prevents neuronal cell death through inhibition of MKK4.

    abstract::The development of neuroprotective agents is necessary for the treatment of neurodegenerative diseases. Here, we report PQA-11, a prenylated quinolinecarboxylic acid (PQA) derivative, as a potent neuroprotectant. PQA-11 inhibits glutamate-induced cell death and caspase-3 activation in hippocampal cultures, as well as ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Ogura M,Kikuchi H,Shakespear N,Suzuki T,Yamaki J,Homma MK,Oshima Y,Homma Y

    更新日期:2019-04-01 00:00:00

  • Effect of the antidepressant minaprine on both forms of monoamine oxidase in the rat.

    abstract::The antidepressant minaprine (3-(2-morpholino-ethylamino) 4-methyl 6-phenyl pyridazine, dihydrochloride) and its main metabolites were examined for their monoamine oxidase (MAO) inhibitory effects in the rat. In our experimental conditions, minaprine displayed in vitro a very weak affinity for brain MAO A and B with I...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Kan JP,Mouget-Goniot C,Worms P,Biziere K

    更新日期:1986-03-15 00:00:00

  • Transplacental passage of isoniazid (INH) and its interaction with fetal tissues of mice.

    abstract::When INH was administered orally or intraperitoneally to pregnant female mice, the concentrations of acetyl INH and acetyl hydrazines did not vary significantly in circulating blood and in amniotic fluid. However, the concentration of INH in the amniotic fluid was significantly higher than that observed in the serum. ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Menon MM,Bhide SV

    更新日期:1983-02-15 00:00:00

  • Evaluation of in vitro PXR-based assays and in silico modeling approaches for understanding the binding of a structurally diverse set of drugs to PXR.

    abstract::The pregnane X-receptor (PXR) is a promiscuous nuclear receptor primarily responsible for the induction of genes from the cytochrome P450 3A family. In this study, we used a previously described PXR/SRC tethered protein to establish two in vitro assays for identifying PXR ligands: automated ligand identification syste...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Xiao L,Nickbarg E,Wang W,Thomas A,Ziebell M,Prosise WW,Lesburg CA,Taremi SS,Gerlach VL,Le HV,Cheng KC

    更新日期:2011-03-01 00:00:00

  • Direct fusion of subunits of heterodimeric nitric oxide sensitive guanylyl cyclase leads to functional enzymes with preserved biochemical properties: evidence for isoform specific activation by ciguates.

    abstract::Nitric oxide sensitive guanylyl cyclase (NOsGC) is a heterodimeric enzyme consisting of an α and a β subunit. Two heterodimeric enzymes are known to be important for NO-signalling in humans: α(1)/β(1) and α(2)/β(1). No difference had so far been detected with respect to their pharmacological properties, but as we show...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Haase N,Haase T,Kraehling JR,Behrends S

    更新日期:2010-12-01 00:00:00

  • Studies on the activation of rat liver microsomal glutathione transferase in isolated hepatocytes.

    abstract::The mechanism of activation of microsomal glutathione transferase in isolated liver cells by diisapropylidene acetone (phorone) was investigated. Phorone (1 mM) causes a time-dependent increase (up to 2.6-fold) in the glutathione transferase activity of microsomes isolated from treated hepatocytes. Since phorone react...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Lundqvist G,Morgenstern R

    更新日期:1992-01-22 00:00:00

  • Repression of inducible nitric oxide synthase and cyclooxygenase-2 by prostaglandin E2 and other cyclic AMP stimulants in J774 macrophages.

    abstract::The enhanced nitric oxide (NO) and prostaglandin (PG) generation of activated macrophages is controlled by glucocorticoid-sensitive inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. Negative feedback regulation of iNOS expression by the products of both pathways has been suggested, but...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Pang L,Hoult JR

    更新日期:1997-02-21 00:00:00

  • Hypocholesterolemic properties of plant indoles. Inhibition of acyl-CoA:cholesterol acyltransferase activity and reduction of serum LDL/VLDL cholesterol levels by glucobrassicin derivatives.

    abstract::Studies were undertaken to investigate the effects of the plant compound indole-3-carbinol (I3C) and its acid condensation products, which are generated in the stomach following ingestion of I3C, on cholesterol homeostasis in mice. Individual acid condensation products were synthesized and purified by HPLC. In vitro e...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Dunn SE,LeBlanc GA

    更新日期:1994-01-20 00:00:00

  • Iron interactions and other biological reactions mediating the physiological and toxic actions of manganese.

    abstract::Chronic exposure to the divalent heavy metals, such as iron, lead, manganese (Mn), and chromium, has been linked to the development of severe, often irreversible neurological disorders and increased vulnerability to developing Parkinson's disease. Although the mechanisms by which these metals elicit or facilitate neur...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Roth JA,Garrick MD

    更新日期:2003-07-01 00:00:00

  • Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats.

    abstract::The present study was designed to evaluate the radioprotective effect of N- acetylcysteine (NAC) on gamma-radiation induced toxicity in hepatic tissue in rat. The cellular changes were estimated using malondialdehyde (MDA, an index of lipid peroxidation), superoxide dismutase (SOD), glutathione peroxidase (GSHPx), red...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Mansour HH,Hafez HF,Fahmy NM,Hanafi N

    更新日期:2008-02-01 00:00:00

  • Inhibition of lipopolysaccharide-stimulated NO production by a novel synthetic compound CYL-4d in RAW 264.7 macrophages involving the blockade of MEK4/JNK/AP-1 pathway.

    abstract::In the present study, a novel synthetic compound 4-(2-(cyclohex-2-enylidene)hydrazinyl)quinolin-2(1H)-one (CYL-4d) was found to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production without affecting cell viability or enzyme activity of expressed inducible NO synthase (iNOS) in RAW 264.7 macrophages. C...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Lin MW,Tsao LT,Chang LC,Chen YL,Huang LJ,Kuo SC,Tzeng CC,Lee MR,Wang JP

    更新日期:2007-06-01 00:00:00

  • Molecular pharmacology of endothelin converting enzymes.

    abstract::A critical processing step in endothelin biosynthesis is the conversion of the intermediate "big endothelin" to its biologically active product catalysed by endothelin converting enzyme (ECE). In this commentary we discuss critically the cellular location, structure, and activity of the isoforms of ECE. The current ev...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Turner AJ,Murphy LJ

    更新日期:1996-01-26 00:00:00

  • Interaction of permanently charged analogs of dopamine with the D-2 dopaminergic receptor.

    abstract::Dopamine can exist in both charged and uncharged forms at physiological pH. At present it is unclear which of these forms is responsible for dopaminergic agonist activity. The purpose of this study was to determine whether permanently charged structural analogs of dopamine containing either a nitrogen, sulfur, or sele...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Wallace RA,Farooqui T,Wallace L,Ares J,Chang YA,Miller D,Uretsky N

    更新日期:1987-11-15 00:00:00

  • Growth factors, cytokines and their receptors as downstream targets of arylhydrocarbon receptor (AhR) signaling pathways.

    abstract::2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental pollutant, which causes a variety of severe health effects, e.g. immunosuppression, hepatotoxicity, and carcinogenesis. The main mediator of TCDD toxicity is the arylhydrocarbon receptor (AhR), which, upon activation, translocates into the nucleu...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Haarmann-Stemmann T,Bothe H,Abel J

    更新日期:2009-02-15 00:00:00

  • Impact of a novel cardioprotective agent on the ischaemia-reperfusion-induced Akt kinase activation.

    abstract::Cardioprotective effect of a free radical-scavenging compound (HO-3073) was examined during ischaemia-reperfusion (IR) in isolated heart perfusion system and its influence on the pro-survival Akt signalling pathway was addressed. Rat hearts were perfused according to the Langendorff method and subjected to a global 25...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Toth A,Kovacs K,Deres P,Halmosi R,Czopf L,Hanto K,Kalai T,Hideg K,Sumegi B,Toth K

    更新日期:2003-12-01 00:00:00

  • Transforming growth factor-beta3 protection of epithelial cells from cycle-selective chemotherapy in vitro.

    abstract::The transforming growth factor-beta (TGF-beta) family of regulatory growth factors can reversibly arrest cell division in the G1 phase of the cell cycle. Previously, TGF-beta3 was shown to protect epithelial cells and hematopoietic cells from cytotoxic damage in vitro and in vivo, and to reduce the severity and durati...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: McCormack ES,Borzillo GV,Ambrosino C,Mak G,Hamablet L,Qu GY,Haley JD

    更新日期:1997-04-25 00:00:00

  • Aspirin and indomethacin reduce lung inflammation of mice exposed to cigarette smoke.

    abstract::Neutrophil accumulation response to cigarette smoke (CS) in humans and animal models is believed to play an important role in pathogenesis of many tobacco-related lung diseases. Here we evaluated the lung anti-inflammatory effect of aspirin and indomethacin in mice exposed to CS. C57BL/6 mice were exposed to four ciga...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Castro P,Nasser H,Abrahão A,Dos Reis LC,Riça I,Valença SS,Rezende DC,Quintas LE,Cavalcante MC,Porto LC,Koatz VL

    更新日期:2009-03-15 00:00:00

  • Depletion of a discrete nuclear glutathione pool by oxidative stress, but not by buthionine sulfoximine. Correlation with enhanced alkylating agent cytotoxicity to human melanoma cells in vitro.

    abstract::The existence of a distinct pool of glutathione in the nucleus of cultured human melanoma cells was demonstrated. Melanoma cell nuclei contained 13-35 pmol of glutathione/10(6) nuclei, or approximately 0.4-1.3% of the total cellular glutathione. This nuclear glutathione pool resisted depletion by buthionine sulfoximin...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Jevtović-Todorović V,Guenthner TM

    更新日期:1992-10-06 00:00:00

  • Mechanism of inhibition of hepatic bile acid uptake by amiloride and 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS).

    abstract::The mechanisms by which amiloride and 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS) inhibit hepatic uptake of cholate and taurocholate (TC) were investigated in isolated rat hepatocytes. Amiloride inhibited Na(+)-dependent uptake of cholate and TC only when hepatocytes were preincubated with amiloride, indicatin...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Anwer MS,Branson AU,Atkinson JM

    更新日期:1991-12-11 00:00:00

  • Mevalonate pathway intermediates downregulate zoledronic acid-induced isopentenyl pyrophosphate and ATP analog formation in human breast cancer cells.

    abstract::Increasing evidence is accumulating that zoledronic acid (ZOL), a nitrogen-containing bisphosphonate (N-BP), is able to affect tumor cells by inhibiting the enzyme farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway (MVP). The consequent accumulation of unprenylated proteins is believed to largely account...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Räikkönen J,Mönkkönen H,Auriola S,Mönkkönen J

    更新日期:2010-03-01 00:00:00

  • Effects of cationic diamidines on polyamine content and uptake on Leishmania infantum in in vitro cultures.

    abstract::The effect of a series of cationic diamidines recently synthesized by Ciba Geigy, bearing diarylic (CGP040215A and CGP039937A) or monoarylic moieties (CGP033829A, CGP035537A and CGP036958A), was analyzed on some metabolic targets and cell proliferation of in vitro cultures of Leishmania infantum promastigotes (insect ...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Calonge M,Johnson R,Balaña-Fouce R,Ordóñez D

    更新日期:1996-09-27 00:00:00

  • Molecular mechanism of L-DNase II activation and function as a molecular switch in apoptosis.

    abstract::The discovery of caspase activation counts as one of the most important finds in the biochemistry of apoptosis. However, targeted disruption of caspases does not impair every type of apoptosis. Other proteases can replace caspases and several so called "caspase independent" pathways are now described. Here we review o...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章,评审


    authors: Torriglia A,Leprêtre C,Padrón-Barthe L,Chahory S,Martin E

    更新日期:2008-12-01 00:00:00

  • Cimetidine-induced seizures in mice. Antagonism by some GABAergic agents.

    abstract::The effects of muscimol, aminooxyacetic acid (AOAA), diamino-n-butyric acid (DABA), baclofen, bicuculline, picrotoxin, strychnine, diazepam, phenobarbitone and phenytoin on cimetidine-induced seizures were studied in mice. Cimetidine (400-1000 mg/kg, i.p.) induced dose-dependent tonic convulsion. Muscimol, AOAA and DA...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Amabeoku GJ,Chikuni O

    更新日期:1993-12-14 00:00:00

  • Deoxyelephantopin inhibits cancer cell proliferation and functions as a selective partial agonist against PPARgamma.

    abstract::Deoxyelephantopin (ESD) was reported to potentiate apoptosis, inhibit invasion and abolish osteoclastogenesis but no target protein was disclosed. Here, we discovered that ESD could significantly inhibit the proliferation of different cancer cells and induce apoptosis and cell cycle arrest at G(2)/M phase in HeLa cell...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Zou G,Gao Z,Wang J,Zhang Y,Ding H,Huang J,Chen L,Guo Y,Jiang H,Shen X

    更新日期:2008-03-15 00:00:00

  • Enzymatic basis of the debrisoquine/sparteine-type genetic polymorphism of drug oxidation. Characterization of bufuralol 1'-hydroxylation in liver microsomes of in vivo phenotyped carriers of the genetic deficiency.

    abstract::The genetically controlled polymorphic oxidation of debrisoquine and sparteine is caused by the absence or functional deficiency of a cytochrome P-450 isozyme. In order to elucidate the mechanisms underlying the differences in cytochrome P-450 function we have studied the 1'-hydroxylation of the prototype drug bufural...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Dayer P,Kronbach T,Eichelbaum M,Meyer UA

    更新日期:1987-12-01 00:00:00

  • A1 adenosine receptor-induced phosphorylation and modulation of transglutaminase 2 activity in H9c2 cells: A role in cell survival.

    abstract::The regulation of tissue transglutaminase (TG2) activity by the GPCR family is poorly understood. In this study, we investigated the modulation of TG2 activity by the A1 adenosine receptor in cardiomyocyte-like H9c2 cells. H9c2 cells were lysed following stimulation with the A1 adenosine receptor agonist N(6)-cyclopen...

    journal_title:Biochemical pharmacology

    pub_type: 杂志文章


    authors: Vyas FS,Hargreaves AJ,Bonner PL,Boocock DJ,Coveney C,Dickenson JM

    更新日期:2016-05-01 00:00:00