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Sci Rep. 2017 Sep 25;7(1):12264. doi: 10.1038/s41598-017-12388-2.

Anti-enterovirus 71 activities of Melissa officinalis extract and its biologically active constituent rosmarinic acid.

Chen SG1, Leu YL2,3,4, Cheng ML5,6,7,8, Ting SC9, Liu CC10,11, Wang SD12, Yang CH1, Hung CY6,7, Sakurai H13, Chen KH14, Ho HY15,16,17.

Author information

1
Graduate Institute of Biomedical Science, Chang Gung University, Guishan, Taoyuan, Taiwan.
2
Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
3
Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital at Linkou, Guishan, Taoyuan, Taiwan.
4
Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.
5
Department of Biomedical Sciences, College of Medicine, Chang Gung University, Guishan, Taoyuan, Taiwan.
6
Healthy Aging Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan.
7
Metabolomics Core Laboratory, Chang Gung University, Guishan, Taoyuan, Taiwan.
8
Clinical Phenome Center, Chang Gung Memorial Hospital at Linkou, Guishan, Taoyuan, Taiwan.
9
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
10
Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
11
Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan.
12
School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
13
Department of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
14
Kidney Research Center, Chang Gung Memorial Hospital, Chang Gung University, School of Medicine, Taoyuan, Taiwan.
15
Healthy Aging Research Center, Chang Gung University, Guishan, Taoyuan, Taiwan. hoh01@mail.cgu.edu.tw.
16
Clinical Phenome Center, Chang Gung Memorial Hospital at Linkou, Guishan, Taoyuan, Taiwan. hoh01@mail.cgu.edu.tw.
17
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan. hoh01@mail.cgu.edu.tw.

Abstract

Enterovirus 71 (EV71) infection is endemic in the Asia-Pacific region. No specific antiviral drug has been available to treat EV71 infection. Melissa officinalis (MO) is a medicinal plant with long history of usage in the European and Middle East. We investigated whether an aqueous solution of concentrated methanolic extract (MOM) possesses antiviral activity. MOM inhibited plaque formation, cytopathic effect, and viral protein synthesis in EV71-infected cells. Using spectral techniques, we identified rosmarinic acid (RA) as a biologically active constituent of MOM. RA reduced viral attachment and entry; cleavage of eukaryotic translation initiation factor 4 G (eIF4G); reactive oxygen species (ROS) generation; and translocation of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) from nucleus to cytoplasm. It alleviated EV71-induced hyperphosphorylation of p38 kinase and EPS15. RA is likely to suppress ROS-mediated p38 kinase activation, and such downstream molecular events as hnRNP A1 translocation and EPS15-regulated membrane trafficking in EV71-infected cells. These findings suggest that MO and its constituent RA possess anti-EV71 activities, and may serve as a candidate drug for therapeutic and prophylactic uses against EV71 infection.

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