Honeysuckle aqueous extract and induced let-7a suppress dengue virus type 2 replication and pathogenesis

Ying Ray Lee; Siao Fen Yeh; Xiao Ming Ruan; Hao Zhang; Sheng Da Hsu; Hsien Da Huang; Chang Chi Hsieh; Yee Shin Lin; Trai Ming Yeh; Hsiao Sheng Liu; Dai Di Gan

doi:10.1016/j.jep.2016.12.049

Honeysuckle aqueous extract and induced let-7a suppress dengue virus type 2 replication and pathogenesis

Ying Ray Lee, Siao Fen Yeh, Xiao Ming Ruan, Hao Zhang, Sheng Da Hsu, Hsien Da Huang, Chang Chi Hsieh, Yee Shin Lin, Trai Ming Yeh, Hsiao Sheng Liu, Dai Di Gan

Research output: Contribution to journal › Article › peer-review

39 Citations (Scopus)

Abstract

Ethnopharmacological relevance Honeysuckle (Lonicera japonica Thunb.), a traditional Chinese herb, has widely been used to treat pathogen infection. However, the underlying-mechanism remains elusive. Aims of the study To reveal the host microRNA (miRNA) profile with the anti-viral activity after honeysuckle treatment. Materials and methods Here we reveal the differentially expressed miRNAs by Solexa^® deep sequencing from the blood of human and mice after the aqueous extract treatment. Among these overexpressed innate miRNAs both in human and mice, let-7a is able to target the NS1 region (nt 3313-3330) of dengue virus (DENV) serotypes 1, 2 and 4 predicated by the target predication software. Results We confirmed that let-7a could target DENV2 at the predicated NS1 sequence and suppress DENV2 replication demonstrated by luciferase-reporter activity, RT-PCR, real-time PCR, Western blotting and plaque assay. ICR-suckling mice consumed honeysuckle aqueous extract either before or after intracranial injection with DENV2 showed decreased levels of NS1 RNA and protein expression accompanied with alleviated disease symptoms, decreased virus load, and prolonged survival time. Similar results were observed when DENV2-infected mice were intracranially injected with let-7a. Conclusion We reveal that honeysuckle attenuates DENV replication and related pathogenesis in vivo through induction of let-7a expression. This study opens a new direction for prevention and treatment of DENV infection through induction of the innate miRNA let-7a by honeysuckle.

Original language	English
Pages (from-to)	109-121
Number of pages	13
Journal	Journal of Ethnopharmacology
Volume	198
DOIs	https://doi.org/10.1016/j.jep.2016.12.049
Publication status	Published - 2017 Feb 23

All Science Journal Classification (ASJC) codes

Pharmacology
Drug Discovery

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10.1016/j.jep.2016.12.049

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@article{6b1bdebf4a4540f4b4b406b4d669148d,

title = "Honeysuckle aqueous extract and induced let-7a suppress dengue virus type 2 replication and pathogenesis",

abstract = "Ethnopharmacological relevance Honeysuckle (Lonicera japonica Thunb.), a traditional Chinese herb, has widely been used to treat pathogen infection. However, the underlying-mechanism remains elusive. Aims of the study To reveal the host microRNA (miRNA) profile with the anti-viral activity after honeysuckle treatment. Materials and methods Here we reveal the differentially expressed miRNAs by Solexa{\textregistered} deep sequencing from the blood of human and mice after the aqueous extract treatment. Among these overexpressed innate miRNAs both in human and mice, let-7a is able to target the NS1 region (nt 3313-3330) of dengue virus (DENV) serotypes 1, 2 and 4 predicated by the target predication software. Results We confirmed that let-7a could target DENV2 at the predicated NS1 sequence and suppress DENV2 replication demonstrated by luciferase-reporter activity, RT-PCR, real-time PCR, Western blotting and plaque assay. ICR-suckling mice consumed honeysuckle aqueous extract either before or after intracranial injection with DENV2 showed decreased levels of NS1 RNA and protein expression accompanied with alleviated disease symptoms, decreased virus load, and prolonged survival time. Similar results were observed when DENV2-infected mice were intracranially injected with let-7a. Conclusion We reveal that honeysuckle attenuates DENV replication and related pathogenesis in vivo through induction of let-7a expression. This study opens a new direction for prevention and treatment of DENV infection through induction of the innate miRNA let-7a by honeysuckle.",

author = "Lee, {Ying Ray} and Yeh, {Siao Fen} and Ruan, {Xiao Ming} and Hao Zhang and Hsu, {Sheng Da} and Huang, {Hsien Da} and Hsieh, {Chang Chi} and Lin, {Yee Shin} and Yeh, {Trai Ming} and Liu, {Hsiao Sheng} and Gan, {Dai Di}",

note = "Funding Information: This work was supported by “Project 985” and “Project 211” grants provided by the Ministry of Education of the People's Republic of China, and the Open Fund of the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China (Grant number# KF-GN-200906) to DDG. It was also supported by grants from the National Science Council of Taiwan (NSC 101-2314-B-705-003-MY3) and Chiayi Christian Hospital. Publisher Copyright: {\textcopyright} 2017 Elsevier Ireland Ltd",

year = "2017",

month = feb,

day = "23",

doi = "10.1016/j.jep.2016.12.049",

language = "English",

volume = "198",

pages = "109--121",

journal = "Journal of Ethnopharmacology",

issn = "0378-8741",

publisher = "Elsevier Ireland Ltd",

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TY - JOUR

T1 - Honeysuckle aqueous extract and induced let-7a suppress dengue virus type 2 replication and pathogenesis

AU - Lee, Ying Ray

AU - Yeh, Siao Fen

AU - Ruan, Xiao Ming

AU - Zhang, Hao

AU - Hsu, Sheng Da

AU - Huang, Hsien Da

AU - Hsieh, Chang Chi

AU - Lin, Yee Shin

AU - Yeh, Trai Ming

AU - Liu, Hsiao Sheng

AU - Gan, Dai Di

N1 - Funding Information: This work was supported by “Project 985” and “Project 211” grants provided by the Ministry of Education of the People's Republic of China, and the Open Fund of the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China (Grant number# KF-GN-200906) to DDG. It was also supported by grants from the National Science Council of Taiwan (NSC 101-2314-B-705-003-MY3) and Chiayi Christian Hospital. Publisher Copyright: © 2017 Elsevier Ireland Ltd

PY - 2017/2/23

Y1 - 2017/2/23

N2 - Ethnopharmacological relevance Honeysuckle (Lonicera japonica Thunb.), a traditional Chinese herb, has widely been used to treat pathogen infection. However, the underlying-mechanism remains elusive. Aims of the study To reveal the host microRNA (miRNA) profile with the anti-viral activity after honeysuckle treatment. Materials and methods Here we reveal the differentially expressed miRNAs by Solexa® deep sequencing from the blood of human and mice after the aqueous extract treatment. Among these overexpressed innate miRNAs both in human and mice, let-7a is able to target the NS1 region (nt 3313-3330) of dengue virus (DENV) serotypes 1, 2 and 4 predicated by the target predication software. Results We confirmed that let-7a could target DENV2 at the predicated NS1 sequence and suppress DENV2 replication demonstrated by luciferase-reporter activity, RT-PCR, real-time PCR, Western blotting and plaque assay. ICR-suckling mice consumed honeysuckle aqueous extract either before or after intracranial injection with DENV2 showed decreased levels of NS1 RNA and protein expression accompanied with alleviated disease symptoms, decreased virus load, and prolonged survival time. Similar results were observed when DENV2-infected mice were intracranially injected with let-7a. Conclusion We reveal that honeysuckle attenuates DENV replication and related pathogenesis in vivo through induction of let-7a expression. This study opens a new direction for prevention and treatment of DENV infection through induction of the innate miRNA let-7a by honeysuckle.

AB - Ethnopharmacological relevance Honeysuckle (Lonicera japonica Thunb.), a traditional Chinese herb, has widely been used to treat pathogen infection. However, the underlying-mechanism remains elusive. Aims of the study To reveal the host microRNA (miRNA) profile with the anti-viral activity after honeysuckle treatment. Materials and methods Here we reveal the differentially expressed miRNAs by Solexa® deep sequencing from the blood of human and mice after the aqueous extract treatment. Among these overexpressed innate miRNAs both in human and mice, let-7a is able to target the NS1 region (nt 3313-3330) of dengue virus (DENV) serotypes 1, 2 and 4 predicated by the target predication software. Results We confirmed that let-7a could target DENV2 at the predicated NS1 sequence and suppress DENV2 replication demonstrated by luciferase-reporter activity, RT-PCR, real-time PCR, Western blotting and plaque assay. ICR-suckling mice consumed honeysuckle aqueous extract either before or after intracranial injection with DENV2 showed decreased levels of NS1 RNA and protein expression accompanied with alleviated disease symptoms, decreased virus load, and prolonged survival time. Similar results were observed when DENV2-infected mice were intracranially injected with let-7a. Conclusion We reveal that honeysuckle attenuates DENV replication and related pathogenesis in vivo through induction of let-7a expression. This study opens a new direction for prevention and treatment of DENV infection through induction of the innate miRNA let-7a by honeysuckle.

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JO - Journal of Ethnopharmacology

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Honeysuckle aqueous extract and induced let-7a suppress dengue virus type 2 replication and pathogenesis

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