Effects of baicalein on Sendai virus in vivo are linked to serum baicalin and its inhibition of hemagglutinin-neuraminidase.
ABSTRACT Parainfluenza viruses are significant respiratory-tract pathogens that are notorious for infecting children. However, there are no clinical drugs to control the infection caused by these viruses. Sendai virus (SeV) belongs to the family Paramyxoviridae and causes fatal pneumonia in mice, its natural host. Baicalein is a flavonoid derived from the root of Scutellaria baicalensis, which is a traditional Chinese medicine that has been used for hundreds of years and has demonstrated a variety of biological activities. Our findings reveal that oral administration of baicalein to mice infected with Sendai virus results in a significant reduction in virus titers in the lungs and protection from death. The in vivo inhibitory effects of baicalein on Sendai virus are determined by baicalin in the serum. The mean IC(50) of baicalin was 0.71 μg/ml in an HA inhibition assay and 3.22 μg/ml in an NA inhibition assay. The mean IC(50) of baicalin in a CPE assay was measured to be 0.70 μg/ml, and significant inhibition was observed in a plaque assay at a concentration of 1.6 μg/ml baicalin in overlay medium, which suggests that baicalein is a potential anti-parainfluenzaviral agent in vivo.
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ABSTRACT: This study rated antiviral activity of Scutellaria baicalensis Georgi (S. baicalensis) extracts against influenza A virus subtypes, for example, pandemic 2009 H1N1, seasonal H1N1 and H3N2. Ethyl acetate (EtOAc) and chloroform extracts inhibited in vitro neuraminidase (NA) enzymatic activity and viral replication more than methanol (MeOH) extract. EtOAc extract demonstrated NA inhibition IC50 values ranging from 73.16 to 487.40 μg/mL and plaque reduction IC50 values ranging from 23.7 to 27.4 μg/mL. Chloroform extract showed antiviral activities with plaque reduction IC50 values ranging from 14.16 to 41.49 μg/mL Time-of-addition assay indicated that EtOAc and chloroform extracts also significantly inhibited virus yields after infection. HPLC analysis demonstrated that baicalin was dominant in the MeOH extract; baicalein and chrysin were rich in the EtOAc and chloroform extracts. Molecular simulation revealed baicalein hydrogen bonding with Glu277 as well as hydrophobic and Van der Waals interactions with Ile222, Arg224, Ser246, and Tyr347 in NA1 active sites of NA1. Baicalein inhibited in vitro replication of influenza A viruses pandemic 2009 H1N1 (IC50 = 0.018 μM) and seasonal 2007 H1N1 using plaque reduction assays. A combination of low-dose baicalein with other anti-influenza agents could be applicable for development of alternative remedies treating influenza A virus infection.Evidence-based Complementary and Alternative Medicine 01/2013; 2013:750803. DOI:10.1155/2013/750803 · 1.88 Impact Factor
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ABSTRACT: Baicalein is a flavonoid derived from the root of Scutellaria baicalensis, a traditional Chinese medicine that has been used for hundreds of years; baicalein has also been demonstrated to have antiviral activity with low toxicity. The synergistic activity of baicalein with ribavirin against influenza virus infections in cell culture and in mice was investigated for the first time in our research. In vitro, maximal synergy at lower concentrations of baicalein (0.125 μg/ml) and ribavirin (12.5 μg/ml) was observed, and the reduced expression of the viral matrix protein (M) gene suggested that drug combinations caused greater inhibition than ribavirin alone, especially the combination of 0.5 μg/ml baicalein and 5 μg/ml ribavirin. In vivo, combinations of baicalein and ribavirin provided a higher survival rate and lower body weight loss. Moreover, fewer inflammatory responses in the lungs of mice infected with virus and treated with baicalein and ribavirin were observed; the mean scores were 1.0, 0.8, and 1.2 with the doses of ribavirin at 50 mg/kg/d combined with baicalein at 100 mg/kg/d, 200 mg/kg/d, and 400 mg/kg/d respectively, while the placebo group had a mean pathology score of 3.2. Thus, the data demonstrates that combinations of baicalein and ribavirin provide better protection against influenza infection than each compound used alone and could potentially be clinically useful.Antiviral research 09/2011; 91(3):314-20. DOI:10.1016/j.antiviral.2011.07.008 · 3.43 Impact Factor
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ABSTRACT: Baicalein, a flavonoid originally isolated from the root of Scutellaria baicalensis Georgi, has numerous pharmacological activities. Up to now, several studies regarding the pharmacokinetic profiles of baicalein have been described, while there is no such study reported in monkey, the species which is more similar to human. The purpose of this study was to investigate the pharmacokinetic profiles of baicalein after oral administration in monkeys. After orally administrating three doses of baicalein in monkeys, multi-peaks of the plasma concentration-time curves were observed and the non-linear pharmacokinetics for baicalein and its metabolite baicalin were found at doses of 50-500mg/kg. In order to calculate the absolute bioavailability, the intravenous pharmacokinetic study was also carried out after intravenous administration of 10mg/kg baicalein. The absolute bioavailability of baicalein in different doses was ranged from 13.1% to 23.0%. In this study, baicalein and baicalin were determined by LC-MS method. The chromatographic separation was performed on Agilent Poroshell 120 SB-C18 column (2.7μm, 2.1×50mm). Baicalein and baicalin were detected by single quadrupole mass spectrometer equipment with electrospray ionization interface with the selected ion monitoring mode. The assay was linear for both baicalein and baicalin with the correlation coefficients>0.99. The intra- and inter-day precisions for baicalein and baicalin were all less than 15% by relative standard deviation. The analytes were stable during samples storage and handling, and no matrix effects were observed. The method we developed in this study was sensitive, precise, stable and producible.Fitoterapia 01/2012; 83(3):532-40. DOI:10.1016/j.fitote.2011.12.019 · 2.22 Impact Factor