Inhibition of RANTES expression by indirubin in influenza virus-infected human bronchial epithelial cells

Mak, Nai‐Ki; Leung, Chung-Yee; Wei, Xiaoyi; Shen, Xiaoling; Wong, Ricky N S; Leung, Ka Nang; Fung, Ming Chiu

doi:10.1016/j.bcp.2003.08.020

Cited by 106 publications

(84 citation statements)

References 26 publications

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“…We observed that suppression of IKK inhibited IB␣ phosphorylation and degradation. These results are consistent with those from a previous study that showed that indirubin could suppress IB␣ phosphorylation in human bronchial epithelial cells infected with influenza virus (22). The authors of that study did not examine the effect of indirubin on NF-B activation.…”

Section: Discussionsupporting

confidence: 83%

“…Our results are in agreement with Danz et al (67) who reported that extracts from the dried leaves of I. tinctoria L significantly inhibited COX-2 activity, preferentially affecting COX-2-catalyzed prostaglandin synthesis. Kunikata et al (21) reported that indirubin suppresses the production of interleukin-6 in murine splenocytes, and Mak et al (22) reported that indirubin suppresses RANTES chemokine production in human bronchial epithelial cells. Because these are also regulated by NF-B (23,68,69), our results may explain their down-regulation.…”

Section: Discussionmentioning

confidence: 99%

“…More recently indirubin was shown to inhibit c-Jun NH 2 -terminal kinase (20). The molecule has anti-inflammatory effects as indicated by its ability to inhibit 2,4,6-trinitro-1-chlorobenzene-induced inflammatory reaction in mice (21) and suppresses the expression of the influenza virus-induced chemokine RANTES in human bronchial epithelial cells (22), suggesting that it may suppress the NF-B activation pathway.…”

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confidence: 99%

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Section: Discussionsupporting

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Section: Discussionmentioning

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Indirubin Enhances Tumor Necrosis Factor-induced Apoptosis through Modulation of Nuclear Factor-κB Signaling Pathway

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et al. 2006

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“…Although S. cusia and C. paniculatum have long been used in traditional Chinese medicine to treat some human diseases, including those caused by infection from several viruses (8)(9)(10), the plant constituents responsible for the antiviral activities remain unknown. To screen for active antiviral compounds, TMV was chosen as a model target and the conventional local lesion assay was used to examine plant extract fractions containing virusinhibitory materials.…”

Section: Identification Of Small-molecule Compounds Inhibiting Tobaccmentioning

confidence: 99%

Seco -pregnane steroids target the subgenomic RNA of alphavirus-like RNA viruses

Wang²,

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Plants have evolved multiple mechanisms to selectively suppress pathogens by production of secondary metabolites with antimicrobial activities. Therefore, direct selections for antiviral compounds from plants can be used to identify new agents with potent antiviral activity but not toxic to hosts. Here, we provide evidence that a class of compounds, seco-pregnane steroid glaucogenin C and its monosugar-glycoside cynatratoside A of Strobilanthes cusia and three new pantasugar-glycosides of glaucogenin C of Cynanchum paniculatum, are effective and selective inhibitors to alphavirus-like positive-strand RNA viruses including plant-infecting tobacco mosaic virus (TMV) and animal-infecting Sindbis virus (SINV), eastern equine encephalitis virus, and Getah virus, but not to other RNA or DNA viruses, yet they were not toxic to host cells. In vivo administration of the compounds protected BALB/c mice from lethal SINV infection without adverse effects on the mice. Using TMV and SINV as models, studies on the action mechanism revealed that the compounds predominantly suppress the expression of viral subgenomic RNA(s) without affecting the accumulation of viral genomic RNA. Our work suggested that the viral subgenomic RNA could be a new target for the discovery of antiviral drugs, and that seco-pregnane steroid and its four glycosides found in the two medicinal herbs have the potential for further development as antiviral agents against alphavirus-like positive-strand RNA viruses.antiviral drugs ͉ Strobilanthes cusia ͉ Cynanchum atratum V iruses replicate in host cells by hijacking the host-cell metabolic machinery. It is therefore difficult for antiviral therapies to inhibit only viral functions but spare host cellular processes. Nevertheless, great progress has been achieved over the past decades in antiviral research and therapy to reduce morbidity and mortality in virus-infected individuals (1, 2), and many antiviral drugs have been approved in recent years, most of which targeted either viral proteins or host cellular proteins. However, some of these compounds might induce the resistance of viruses to them and cause cell toxicity (3-5). The continuing emergence of highly pathogenic viruses like avian influenza viruses and severe acute respiratory syndrome coronavirus underscores the importance of advancing the search for effective antiviral agents. Plants have evolved constitutive and inducible defense mechanisms by producing a vast array of secondary metabolites against various microbial pathogens (6). Many herbaceous plants have been used in traditional Chinese medicine to treat viral diseases (7). It is conceivable that antiviral compounds would occur in plants as part of their innate defense arsenal, and the vast assortment of secondary metabolites could serve as a large pool for screening for previously undescribed antiviral compounds with a selective target spectrum and nontoxic to the host plants. Here, we provide evidence that a class of compounds, the seco-pregnane steroid and its glycosides from Strobilanthe...

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“…Since the late 20th century, more and more compounds were found in IIR, including alkaloids (7)(8)(9)(10)(11), sucrose (9), organic acids (7,9) and glycosides (9,12 shown to have potent anti-influenza virus activity by inhibition of RANTES (also known as CCL5) expression (13). Yamada previously reported a glycoprotein from R. isatidis that showed useful antiviral activities in the therapy and prevention of virus infection in vitro and in vivo (14).…”

Section: Introductionmentioning

confidence: 99%

In vitro inhibition of influenza virus infection by a crude extract from Isatis indigotica root resulting in the prevention of viral attachment

et al. 2011

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Inhibition of RANTES expression by indirubin in influenza virus-infected human bronchial epithelial cells

Cited by 106 publications

References 26 publications

Indirubin Enhances Tumor Necrosis Factor-induced Apoptosis through Modulation of Nuclear Factor-κB Signaling Pathway

Indirubin Enhances Tumor Necrosis Factor-induced Apoptosis through Modulation of Nuclear Factor-κB Signaling Pathway

Seco -pregnane steroids target the subgenomic RNA of alphavirus-like RNA viruses

In vitro inhibition of influenza virus infection by a crude extract from Isatis indigotica root resulting in the prevention of viral attachment

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