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Virology Journal
Published in: Virology Journal 1/2017

Open Access 01-12-2017 | Research

Berberine inhibits enterovirus 71 replication by downregulating the MEK/ERK signaling pathway and autophagy

Authors: Huiqiang Wang, Ke Li, Linlin Ma, Shuo Wu, Jin Hu, Haiyan Yan, Jiandong Jiang, Yuhuan Li

Published in: Virology Journal | Issue 1/2017

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Abstract

Background

The MEK-ERK signaling pathway and autophagy play an important role for enterovirus71(EV71) replication. Inhibition of MEK-ERK signaling pathway and autophagy is shown to impair EV71 replication. Berberine (BBR), an isoquinoline alkaloid isolated from Berberis vulgaris L., has been reported to have ability to regulate this signaling pathway and autophagy. Herein, we want to determine whether berberine can inhibit EV71 infection by downregulating the MEK/ERK signaling pathway and autophagy.

Methods

The antiviral effect of berberine was determined by cytopathic effect (CPE) assay, western blotting assay and qRT-PCR assay. The mechanism of BBR anti-virus was determined by western blotting assay and immunofluorescence assay.

Results

We showed that berberine does-dependently reduced EV71 RNA and protein synthesis, which was, at least in part, the result of inhibition of activation of MEK/ERK signaling pathway. Furthermore, we found that berberine suppressed the EV71-induced autophagy by activating AKT protein and inhibiting the phosphorylation of JNK and PI3KIII.

Conclusions

BBR inhibited EV71 replication by downregulating autophagy and MEK/ERK signaling pathway. These findings suggest that BBR may be a potential agent or supplement against EV71 infection.
Literature
1.
Wang HQ, Meng S, Li ZR, Peng ZG, Han YX, Guo SS, Cui XL, Li YH, Jiang JD. The antiviral effect of 7-hydroxyisoflavone against enterovirus 71 in vitro. J Asian Nat Prod Res. 2013;15(4):382–9.CrossRefPubMed
2.
McMinn PC. Recent advances in the molecular epidemiology and control of human enterovirus 71 infection. Curr Opin Virol. 2012;2(2):199–205.CrossRefPubMed
3.
Wang X, Zhu C, Bao W, Zhao K, Niu J, Yu XF, Zhang W. Characterization of full-length enterovirus 71 strains from severe and mild disease patients in northeastern China. PLoS One. 2012;7(3):e32405.CrossRefPubMedPubMedCentral
4.
Wang B, Zhang H, Zhu M, Luo Z, Peng Y. MEK1-ERKs signal cascade is required for the replication of Enterovirus 71 (EV71). Antiviral Res. 2012;93(1):110–7.CrossRefPubMed
5.
6.
Tung WH, Hsieh HL, Yang CM. Enterovirus 71 induces COX-2 expression via MAPKs, NF-kappaB, and AP-1 in SK-N-SH cells: Role of PGE(2) in viral replication. Cell Signal. 2010;22(2):234–46.CrossRefPubMed
7.
Shi W, Hou X, Peng H, Zhang L, Li Y, Gu Z, Jiang Q, Shi M, Ji Y, Jiang J. MEK/ERK signaling pathway is required for enterovirus 71 replication in immature dendritic cells. Virol J. 2014;11:227.CrossRefPubMedPubMedCentral
8.
Mouna L, Hernandez E, Bonte D, Brost R, Amazit L, Delgui LR, Brune W, Geballe AP, Beau I, Esclatine A. Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins. Autophagy. 2016;12(2):327–42.CrossRefPubMed
9.
Liu C, Qu A, Han X, Wang Y. HCV core protein represses the apoptosis and improves the autophagy of human hepatocytes. Int J Clin Exp Med. 2015;8(9):15787–93.PubMedPubMedCentral
10.
Talloczy Z, Jiang W, Virgin HW, Leib DA, Scheuner D, Kaufman RJ, Eskelinen EL, Levine B. Regulation of starvation- and virus-induced autophagy by the eIF2alpha kinase signaling pathway. Proc Natl Acad Sci U S A. 2002;99(1):190–5.CrossRefPubMed
11.
Wong J, Zhang J, Si X, Gao G, Mao I, McManus BM, Luo H. Autophagosome supports coxsackievirus B3 replication in host cells. J Virol. 2008;82(18):9143–53.CrossRefPubMedPubMedCentral
12.
Zhou Z, Jiang X, Liu D, Fan Z, Hu X, Yan J, Wang M, Gao GF. Autophagy is involved in influenza a virus replication. Autophagy. 2009;5(3):321–8.CrossRefPubMed
13.
Espert L, Denizot M, Grimaldi M, Robert-Hebmann V, Gay B, Varbanov M, Codogno P, Biard-Piechaczyk M. Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4. J Clin Invest. 2006;116(8):2161–72.CrossRefPubMedPubMedCentral
14.
Huang SC, Chang CL, Wang PS, Tsai Y, Liu HS. Enterovirus 71-induced autophagy detected in vitro and in vivo promotes viral replication. J Med Virol. 2009;81(7):1241–52.CrossRefPubMed
15.
Xi X, Zhang X, Wang B, Wang T, Wang J, Huang H, Jin Q, Zhao Z. The interplays between autophagy and apoptosis induced by enterovirus 71. PLoS One. 2013;8(2):e56966.CrossRefPubMedPubMedCentral
16.
Fu Y, Xu W, Chen D, Feng C, Zhang L, Wang X, Lv X, Zheng N, Jin Y, Wu Z. Enterovirus 71 induces autophagy by regulating has-miR-30a expression to promote viral replication. Antiviral Res. 2015;124:43–53.CrossRefPubMed
17.
Lee YR, Wang PS, Wang JR, Liu HS. Enterovirus 71-induced autophagy increases viral replication and pathogenesis in a suckling mouse model. J Biomed Sci. 2014;21:80.CrossRefPubMedPubMedCentral
18.
Rabbani GH. Mechanism and treatment of diarrhoea due to vibrio cholerae and Escherichia coli: roles of drugs and prostaglandins. Dan Med Bull. 1996;43(2):173–85.PubMed
19.
Peng L, Kang S, Yin Z, Jia R, Song X, Li L, Li Z, Zou Y, Liang X, He C, Ye G, Yin L, Shi F, Lv C, Jing B. Antibacterial activity and mechanism of berberine against Streptococcus agalactiae. Int J Clin Exp Pathol. 2015;8(5):5217–23.PubMedPubMedCentral
20.
Chun YT, Yip TT, Lau KL, Kong YC, Sankawa U. A biochemical study on the hypotensive effect of berberine in rats. Gen Pharmacol. 1979;10(3):177–82.CrossRefPubMed
21.
Shin HB, Choi MS, Yi CM, Lee J, Kim NJ, Inn KS. Inhibition of respiratory syncytial virus replication and virus-induced p38 kinase activity by berberine. Int Immunopharmacol. 2015;27(1):65–8.CrossRefPubMed
22.
Song S, Qiu M, Chu Y, Chen D, Wang X, Su A, Wu Z. Downregulation of cellular c-Jun N-terminal protein kinase and NF-kappaB activation by berberine may result in inhibition of herpes simplex virus replication. Antimicrob Agents Chemother. 2014;58(9):5068–78.CrossRefPubMedPubMedCentral
23.
Liu Q, Xu X, Zhao M, Wei Z, Li X, Zhang X, Liu Z, Gong Y, Shao C. Berberine induces senescence of human glioblastoma cells by downregulating the EGFR-MEK-ERK signaling pathway. Mol Cancer Ther. 2015;14(2):355–63.CrossRefPubMed
24.
Fan X, Wang J, Hou J, Lin C, Bensoussan A, Chang D, Liu J, Wang B. Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway. J Transl Med. 2015;13:92.CrossRefPubMedPubMedCentral
25.
Deng Y, Xu J, Zhang X, Yang J, Zhang D, Huang J, Lv P, Shen W, Yang Y. Berberine attenuates autophagy in adipocytes by targeting BECN1. Autophagy. 2014;10(10):1776–86.CrossRefPubMedPubMedCentral
26.
Mahata S, Bharti AC, Shukla S, Tyagi A, Husain SA, Das BC. Berberine modulates AP-1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells. Mol Cancer. 2011;10:39.CrossRefPubMedPubMedCentral
27.
Hayashi K, Minoda K, Nagaoka Y, Hayashi T, Uesato S. Antiviral activity of berberine and related compounds against human cytomegalovirus. Bioorg Med Chem Lett. 2007;17(6):1562–4.CrossRefPubMed
28.
Rodemann HP, Dittmann K, Toulany M. Radiation-induced EGFR-signaling and control of DNA-damage repair. Int J Radiat Biol. 2007;83(11-12):781–91.CrossRefPubMed
29.
Wei Y, Fang W, Wan Z, Wang K, Yang Q, Cai X, Shi L, Yang Z. Antiviral effects against EV71 of pimprinine and its derivatives isolated from Streptomyces sp. Virol J. 2014;11:195.CrossRefPubMedPubMedCentral
30.
Chen X, Wang C, Xu L, Wang W, Yang G, Tan RX, Li E, Jin Y. A laboratory evaluation of medicinal herbs used in china for the treatment of hand, foot, and mouth disease. Evid Based Complement Alternat Med. 2013;2013:504563.PubMedPubMedCentral
31.
De Clercq E. Highlights in antiviral drug research: antivirals at the horizon. Med Res Rev. 2013;33(6):1215–48.PubMed
32.
Thibaut HJ, De Palma AM, Neyts J. Combating enterovirus replication: state-of-the-art on antiviral research. Biochem Pharmacol. 2012;83(2):185–92.CrossRefPubMed
33.
Sun T, Liu R, Cao YX. Vasorelaxant and antihypertensive effects of formononetin through endothelium-dependent and -independent mechanisms. Acta Pharmacol Sin. 2011;32(8):1009–18.CrossRefPubMedPubMedCentral
34.
Yu R, Zhang ZQ, Wang B, Jiang HX, Cheng L, Shen LM. Berberine-induced apoptotic and autophagic death of HepG2 cells requires AMPK activation. Cancer Cell Int. 2014;14:19.CrossRef
Metadata
Title
Berberine inhibits enterovirus 71 replication by downregulating the MEK/ERK signaling pathway and autophagy
Authors
Huiqiang Wang
Ke Li
Linlin Ma
Shuo Wu
Jin Hu
Haiyan Yan
Jiandong Jiang
Yuhuan Li
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2017
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-016-0674-4

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