Effects of baicalein on Sendai virus in vivo are linked to serum baicalin and its inhibition of hemagglutinin-neuraminidase

School of Life Science and Technology, China Pharmaceutical University, Tong Jia Xiang, Nanjing, China.
Archives of Virology (Impact Factor: 2.39). 02/2011; 156(5):793-801. DOI: 10.1007/s00705-011-0917-z
Source: PubMed


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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    • "It has also been shown that ~90% of baicalein administered is metabolized to baicalin17, and hence, it is necessary to investigate the role of baicalin in any particular medical condition. "
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    ABSTRACT: Baicalin, a flavonoid derived from Scutellaria baicalensis, is the main metabolite of baicalein released following administration in different animal models and human. We previously reported the antiviral activity of baicalein against dengue virus (DENV). Here, we examined the anti-DENV properties of baicalin in vitro, and described the inhibitory potentials of baicalin at different steps of DENV-2 (NGC strain) replication. Our in vitro antiviral experiments showed that baicalin inhibited virus replication at IC50 = 13.5 ± 0.08 μg/ml with SI = 21.5 following virus internalization by Vero cells. Baicalin exhibited virucidal activity against DENV-2 extracellular particles at IC50 = 8.74 ± 0.08 μg/ml and showed anti-adsorption effect with IC50 = 18.07 ± 0.2 μg/ml. Our findings showed that baicalin as the main metabolite of baicalein exerting in vitro anti-DENV activity. Further investigations on baicalein and baicalin to deduce its antiviral therapeutic effects are warranted.
    Full-text · Article · Jun 2014 · Scientific Reports
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    • "Baicalin, baicalein, wogonin, wogonin 7-O- glucuronide, oroxylin A, oroxylin A 7-O-glucuronide, apigenin, and chrysin are major and bioactive components of S. baicalensis [23]. Baicalin and baicalein inhibit viral replication of parainfluenza [24], influenza A [25], hepatitis B [26], HIV-1 [27], and SARS coronavirus [28]. Wogonin inhibits hepatitis B surface antigen secretion while reducing HBV-DNA level in vitro, as confirmed by the animal model infected with duck hepatitis B virus [29]. "
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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.
    Full-text · Article · Jun 2013 · Evidence-based Complementary and Alternative Medicine
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    • "The other possible mechanism of action for baicalein includes interaction with JEV structural and/or non-structural protein(s). It has previously been shown that baicalein affects Sendai virus replication through inhibition of virus hemagglutinin-neuraminidase activity [13]. Other studies have also shown that baicalein binds to HIV-1 integrase and reverse transcriptase enzymes [25,26]. "
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    ABSTRACT: Japanese encephalitis (JE), a mosquito-borne viral disease, is endemic to the entire east and southeast Asia, and some other parts of the world. Currently, there is no effective therapeutic available for JE; therefore, finding the effective antiviral agent against JEV replication is crucial. In the present study, the in vitro antiviral activity of baicalein and quercetin, two purportedly antiviral bioflavonoids, was evaluated against Japanese encephalitis virus (JEV) replication in Vero cells. Anti-JEV activities of these compounds were examined on different stages of JEV replication cycle. The effects of the compounds on virus replication were determined by foci forming unit reduction assay (FFURA) and quantitative RT-PCR. Baicalein showed potent antiviral activity with IC50 = 14.28 µg/mL when it was introduced to the Vero cells after adsorption of JEV. Quercetin exhibited weak anti-JEV effects with IC50 = 212.1 µg/mL when the JEV infected cells were treated with the compound after virus adsorption. However, baicalein exhibited significant effect against JEV adsorption with IC50 = 7.27 µg/mL while quercetin did not show any anti-adsorption activity. Baicalein also exhibited direct extracellular virucidal activity on JEV with IC50 = 3.44 µg/mL. However, results of quantitative RT-PCR experiments confirmed the findings from FFURA. This study demonstrated that baicalein should be considered as an appropriate candidate for further investigations, such as the study of molecular and cellular mechanism(s) of action and in vivo evaluation for the development of an effective antiviral compound against Japanese encephalitis virus.
    Full-text · Article · Dec 2012 · International Journal of Molecular Sciences
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