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Anti-influenza A virus activity of rhein through regulating oxidative stress, TLR4, Akt, MAPK, and NF-κB signal pathways.

Identifieur interne : 000A22 ( Main/Exploration ); précédent : 000A21; suivant : 000A23

Anti-influenza A virus activity of rhein through regulating oxidative stress, TLR4, Akt, MAPK, and NF-κB signal pathways.

Auteurs : Qian-Wen Wang [République populaire de Chine] ; Yun Su [République populaire de Chine] ; Jiang-Tao Sheng [République populaire de Chine] ; Li-Ming Gu [République populaire de Chine] ; Ying Zhao [République populaire de Chine] ; Xiao-Xuan Chen [République populaire de Chine] ; Cheng Chen [République populaire de Chine] ; Wei-Zhong Li [États-Unis] ; Kang-Sheng Li [République populaire de Chine] ; Jian-Ping Dai [République populaire de Chine]

Source :

RBID : pubmed:29385192

Descripteurs français

English descriptors

Abstract

Rhein, an anthraquinone compound existing in many traditional herbal medicines, has anti-inflammatory, antioxidant, antitumor, antiviral, hepatoprotective, and nephroprotective activities, but its anti-influenza A virus (IAV) activity is ambiguous. In the present study, through plaque inhibition assay, time-of-addition assay, antioxidant assay, qRT-PCR, ELISA, and western blotting assays, we investigated the anti-IAV effect and mechanism of action of rhein in vitro and in vivo. The results showed that rhein could significantly inhibit IAV adsorption and replication, decrease IAV-induced oxidative stress, activations of TLR4, Akt, p38, JNK MAPK, and NF-κB pathways, and production of inflammatory cytokines and matrix metalloproteinases in vitro. Oxidant H2O2 and agonists of TLR4, Akt, p38/JNK and IKK/NF-κB could significantly antagonize the inhibitory effects of rhein on IAV-induced cytopathic effect (CPE) and IAV replication. Through an in vivo test in mice, we also found that rhein could significantly improve the survival rate, lung index, pulmonary cytokines, and pulmonary histopathological changes. Rhein also significantly decreased pulmonary viral load at a high dose. In conclusion, rhein can inhibit IAV adsorption and replication, and the mechanism of action to inhibit IAV replication may be due to its ability to suppress IAV-induced oxidative stress and activations of TLR4, Akt, p38, JNK MAPK, and NF-κB signal pathways.

DOI: 10.1371/journal.pone.0191793
PubMed: 29385192


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<term>Cytokines (biosynthesis)</term>
<term>Dogs</term>
<term>Female</term>
<term>Humans</term>
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<front>
<div type="abstract" xml:lang="en">Rhein, an anthraquinone compound existing in many traditional herbal medicines, has anti-inflammatory, antioxidant, antitumor, antiviral, hepatoprotective, and nephroprotective activities, but its anti-influenza A virus (IAV) activity is ambiguous. In the present study, through plaque inhibition assay, time-of-addition assay, antioxidant assay, qRT-PCR, ELISA, and western blotting assays, we investigated the anti-IAV effect and mechanism of action of rhein in vitro and in vivo. The results showed that rhein could significantly inhibit IAV adsorption and replication, decrease IAV-induced oxidative stress, activations of TLR4, Akt, p38, JNK MAPK, and NF-κB pathways, and production of inflammatory cytokines and matrix metalloproteinases in vitro. Oxidant H2O2 and agonists of TLR4, Akt, p38/JNK and IKK/NF-κB could significantly antagonize the inhibitory effects of rhein on IAV-induced cytopathic effect (CPE) and IAV replication. Through an in vivo test in mice, we also found that rhein could significantly improve the survival rate, lung index, pulmonary cytokines, and pulmonary histopathological changes. Rhein also significantly decreased pulmonary viral load at a high dose. In conclusion, rhein can inhibit IAV adsorption and replication, and the mechanism of action to inhibit IAV replication may be due to its ability to suppress IAV-induced oxidative stress and activations of TLR4, Akt, p38, JNK MAPK, and NF-κB signal pathways.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region>
<li>Maryland</li>
</region>
<settlement>
<li>College Park (Maryland)</li>
</settlement>
<orgName>
<li>Université du Maryland</li>
</orgName>
</list>
<tree>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Wang, Qian Wen" sort="Wang, Qian Wen" uniqKey="Wang Q" first="Qian-Wen" last="Wang">Qian-Wen Wang</name>
</noRegion>
<name sortKey="Chen, Cheng" sort="Chen, Cheng" uniqKey="Chen C" first="Cheng" last="Chen">Cheng Chen</name>
<name sortKey="Chen, Xiao Xuan" sort="Chen, Xiao Xuan" uniqKey="Chen X" first="Xiao-Xuan" last="Chen">Xiao-Xuan Chen</name>
<name sortKey="Dai, Jian Ping" sort="Dai, Jian Ping" uniqKey="Dai J" first="Jian-Ping" last="Dai">Jian-Ping Dai</name>
<name sortKey="Gu, Li Ming" sort="Gu, Li Ming" uniqKey="Gu L" first="Li-Ming" last="Gu">Li-Ming Gu</name>
<name sortKey="Li, Kang Sheng" sort="Li, Kang Sheng" uniqKey="Li K" first="Kang-Sheng" last="Li">Kang-Sheng Li</name>
<name sortKey="Sheng, Jiang Tao" sort="Sheng, Jiang Tao" uniqKey="Sheng J" first="Jiang-Tao" last="Sheng">Jiang-Tao Sheng</name>
<name sortKey="Su, Yun" sort="Su, Yun" uniqKey="Su Y" first="Yun" last="Su">Yun Su</name>
<name sortKey="Zhao, Ying" sort="Zhao, Ying" uniqKey="Zhao Y" first="Ying" last="Zhao">Ying Zhao</name>
</country>
<country name="États-Unis">
<region name="Maryland">
<name sortKey="Li, Wei Zhong" sort="Li, Wei Zhong" uniqKey="Li W" first="Wei-Zhong" last="Li">Wei-Zhong Li</name>
</region>
</country>
</tree>
</affiliations>
</record>

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