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 journalArticle

5 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 languageEnglish
Pages (from-to)109-121
Number of pages13
JournalJournal of Ethnopharmacology
Volume198
DOIs
Publication statusPublished - 2017 Feb 23

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Lonicera
Dengue Virus
Virus Replication
MicroRNAs
High-Throughput Nucleotide Sequencing
Inbred ICR Mouse
Virus Diseases
Luciferases
Real-Time Polymerase Chain Reaction
Therapeutics
Software
Western Blotting
RNA
Viruses
Polymerase Chain Reaction
Injections
Survival
Infection

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery

Cite this

Lee, Ying Ray ; Yeh, Siao Fen ; Ruan, Xiao Ming ; Zhang, Hao ; Hsu, Sheng Da ; Huang, Hsien Da ; Hsieh, Chang Chi ; Lin, Yee-Shin ; Yeh, Trai-Ming ; Liu, Hsiao-Sheng ; Gan, Dai Di. / Honeysuckle aqueous extract and induced let-7a suppress dengue virus type 2 replication and pathogenesis. In: Journal of Ethnopharmacology. 2017 ; Vol. 198. pp. 109-121.
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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{\circledR} 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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Honeysuckle aqueous extract and induced let-7a suppress dengue virus type 2 replication and pathogenesis. / Lee, Ying Ray; Yeh, Siao Fen; Ruan, Xiao Ming; Zhang, Hao; Hsu, Sheng Da; Huang, Hsien Da; Hsieh, Chang Chi; Lin, Yee-Shin; Yeh, Trai-Ming; Liu, Hsiao-Sheng; Gan, Dai Di.

In: Journal of Ethnopharmacology, Vol. 198, 23.02.2017, p. 109-121.

Research output: Contribution to journalArticle

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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

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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