Lariciresinol-4-O-β-D-glucopyranoside from the root of Isatis indigotica inhibits influenza A virus-induced pro-inflammatory response

Li, Jing; Zhou, Beixian; Li, Chufang; Chen, QiaoYan; Wang, Yutao; Li, Zhengtu; Chen, Tingting; Yang, Chunguang; Jiang, Zhi‐Hong; Zhong, Nanshan; Yang, Zifeng; Chen, Rongchang

doi:10.1016/j.jep.2015.08.037

Cited by 71 publications

(51 citation statements)

References 43 publications

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“…It is well known that 4CL family proteins catalyse the conversion of CoA esters of a series of hydroxycinnamic acid in complex phenylpropanoid metabolism (Dixon and Reddy, ; Li et al ., ; Sun et al ., ; Zhao and Dixon, ). Coupling the in vitro enzyme kinetics with in vivo functional features, our result showed that 4CL3 acquired a distinct role in lignan metabolism in I. indigotica, which was dominatingly via the conversion of caffeic acid catalysed by 4CL3 (Figure ).…”

Section: Resultsmentioning

confidence: 99%

“…However, it is still far away from a fully understanding of lignan biosynthesis. It is well known that multiple protein families are involved in phenylpropanoid pathways and have overlapping yet distinct roles in phenylpropanoid metabolism (Li et al ., ; Staniek et al ., ). There has not been a comprehensive genetic study on the impact of these isoforms on lignan metabolism.…”

Section: Introductionmentioning

confidence: 99%

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Dynamic metabolic and transcriptomic profiling of methyl jasmonate‐treated hairy roots reveals synthetic characters and regulators of lignan biosynthesis in Isatis indigotica Fort

Zhang

Chen

Zhou

et al. 2016

Plant Biotechnology Journal

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SummaryA molecular description of lignan biosynthesis in Isatis indigotica displaying its synthetic characteristics and regulatory mechanism is of great importance for the improvement of the production of this class of active compounds. To discover the potential key catalytic steps and regulatory genes, I. indigotica hairy roots elicited by methyl jasmonate (MeJA) were used as a source of systematic variation for exploring the metabolic/transcriptional changes and candidate genes that might play key roles in lignan biosynthesis. The reprogramming modulated by MeJA was classified into three distinct phases, referred to as signal responding, transcriptional activation of metabolic pathways and accumulation of metabolites. Candidate genes were pooled according to the three phases and applied to co‐expression network analysis. In total, 17 genes were identified as hub genes. 4CL3 was selected to validate its impact on lignan biosynthesis. RNAi of 4CL3 resulted in a significant reduction in lignan production. Taken together with its catalytic property, a major route of lignan biosynthesis in I. indigotica was highlighted, which was catalysed by 4CL3 via the esterization of caffeic acid. In conclusion, this study provides new insights into lignan biosynthesis as well as potential targets for metabolic engineering in I. indigotica.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dynamic metabolic and transcriptomic profiling of methyl jasmonate‐treated hairy roots reveals synthetic characters and regulators of lignan biosynthesis in Isatis indigotica Fort

Zhang

Chen

Zhou

et al. 2016

Plant Biotechnology Journal

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“…Our previous studies have demonstrated that a lignan from I . indigotica , lariciresinol-4-β-D-glucopyranoside, exhibited potent inhibitory activity against influenza virus A/PR/8/34(H1N1), with 50% inhibitory concentrations (IC 50 ) of 50 μg/mL and selectively inedx (SI) more than 4, while it showed low cytotoxic potency towards MDCK cells for which the CC 50 exceeded 200 μg/mL [26]. Furthermore, lariciresinol-4-β-D-glucopyranoside suppressed influenza A (H1N1) virus-infected or TNF-α-stimulated activation of NF-κB in a NF-κB luciferase reporter stable HEK293 cell line.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, lariciresinol-4-β-D-glucopyranoside suppressed influenza A (H1N1) virus-infected or TNF-α-stimulated activation of NF-κB in a NF-κB luciferase reporter stable HEK293 cell line. Meanwhile, the increased level of pro-inflammatory genes in influenza A H1N1 or H9N2 viruses-infected cells, such as TNF-α, IL-6, IP-10 and IL-8, were inhibted by lariciresinol-4-β-D-glucopyranoside treatment [26]. Therefore, our previous results suggested that lariciresinol-4-β-D-glucopyranoside impaired influenza virus propagation and suppressed the human or avian influenza virus-induced host inflammatory response via the regulation of NF-κB activation [26].…”

Section: Introductionmentioning

confidence: 99%

“…Meanwhile, the increased level of pro-inflammatory genes in influenza A H1N1 or H9N2 viruses-infected cells, such as TNF-α, IL-6, IP-10 and IL-8, were inhibted by lariciresinol-4-β-D-glucopyranoside treatment [26]. Therefore, our previous results suggested that lariciresinol-4-β-D-glucopyranoside impaired influenza virus propagation and suppressed the human or avian influenza virus-induced host inflammatory response via the regulation of NF-κB activation [26]. In this study, we used RNA-seq technology to systematically assess the transcriptome profile of influenza A virus-infected lung epithelial (A549) cells following lariciresinol-4-β-D-glucopyranoside treatment, which may result in gaining a comprehensive understanding the mechanism of lariciresinol-4-β-D-glucopyranoside against influenza A virus infection.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptome profiling of influenza A virus-infected lung epithelial (A549) cells with lariciresinol-4-β-D-glucopyranoside treatment

Zhou

Liang

et al. 2017

PLoS ONE

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The influenza A virus is an acute contagious pathogen that affects the human respiratory system and can cause severe lung disease and even death. Lariciresinol-4-β-D-glucopyranoside is a lignan that is extracted from Isatis indigotica, which is a medicinal herb plant that was commonly applied to treat infections, the common cold, fever and inflammatory diseases. Our previous study demonstrated that lariciresinol-4-β-D-glucopyranoside possesses anti-viral and anti-inflammatory properties. However, the comprehensive and detailed mechanisms that underlie the effect of lariciresinol-4-β-D-glucopyranoside interventions against influenza virus infection remain to be elucidated. In this study, we employed high-throughput RNA sequencing (RNA-seq) to investigate the transcriptomic responses of influenza A virus-infected lung epithelial (A549) cells with lariciresinol-4-β-D-glucopyranoside treatment. The transcriptome data show that infection with influenza A virus prompted the activation of 368 genes involved in RIG-I signalling, the inflammatory response, interferon α/β signalling and gene expression that was not affected by lariciresinol-4-β-D-glucopyranoside treatment. Lariciresinol-4-β-D-glucopyranoside exerted its pharmacological actions on the immune system, signal transduction, cell cycle and metabolism, which may be an underlying defense mechanism against influenza virus infection. In addition, 166 differentially expressed genes (DEGs) were uniquely expressed in lariciresinol-4-β-D-glucopyranoside-treated cells, which were concentrated in the cell cycle, DNA repair, chromatin organization, gene expression and biosynthesis domains. Among them, six telomere-associated genes were up-regulated by lariciresinol-4-β-D-glucopyranoside treatment, which have been implicated in telomere regulation and stability. Collectively, we employed RNA-seq analysis to provide comprehensive insight into the mechanism of lariciresinol-4-β-D-glucopyranoside against influenza virus infection.

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Development of anti‐influenza agents from natural products

Zhang

Morris‐Natschke

Cheng

et al. 2020

Medicinal Research Reviews

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Lariciresinol-4-O-β-D-glucopyranoside from the root of Isatis indigotica inhibits influenza A virus-induced pro-inflammatory response

Cited by 71 publications

References 43 publications

Dynamic metabolic and transcriptomic profiling of methyl jasmonate‐treated hairy roots reveals synthetic characters and regulators of lignan biosynthesis in Isatis indigotica Fort

Dynamic metabolic and transcriptomic profiling of methyl jasmonate‐treated hairy roots reveals synthetic characters and regulators of lignan biosynthesis in Isatis indigotica Fort

Transcriptome profiling of influenza A virus-infected lung epithelial (A549) cells with lariciresinol-4-β-D-glucopyranoside treatment

Development of anti‐influenza agents from natural products

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