Stimulation of TRAF6/TAK1 degradation and inhibition of JNK/AP-1 signalling by ginsenoside Rg3 attenuates hepatitis B virus replication

Kang, Li‐Jung; Choi, Yoon-Hee; Lee, Seong-Gene

doi:10.1016/j.biocel.2013.08.016

Cited by 50 publications

(41 citation statements)

References 32 publications

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“…Our data suggest that G‐Rg3 is a valuable new candidate for treating HCV patients either as a monotherapy or in combination with sofosbuvir. Possible application of G‐Rg3 for other viral infections is presently being investigated …”

Section: Discussionmentioning

confidence: 99%

“…Possible application of G-Rg3 for other viral infections is presently being investigated. (38,39) Despite the promising potential of G-Rg3 as a multifunctional drug candidate including anticancer, (40) antiangiogenesis, (41) liver protection, (42) immune enhancement, and hypertension management, with a neuroprotective effect, (43) there could be some concern FIG. 7.…”

Section: Discussionmentioning

confidence: 99%

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Ginsenoside Rg3 restores hepatitis C virus–induced aberrant mitochondrial dynamics and inhibits virus propagation

et al. 2017

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Hepatitis C virus (HCV) alters mitochondrial dynamics associated with persistent viral infection and suppression of innate immunity. Mitochondrial dysfunction is also a pathologic feature of direct-acting antiviral (DAA) treatment. Despite the high efficacy of DAAs, their treatment of patients with chronic hepatitis C in interferon-sparing regimens occasionally produces undesirable side effects such as fatigue, migraine and other conditions, which may be linked to mitochondrial dysfunction. Here we show that clinically prescribed DAAs, including Sofosbuvir, affect mitochondrial dynamics. To counter these adverse effects, we examined HCV- and DAA-induced aberrant mitochondrial dynamics modulated by ginsenoside, which is known to support healthy mitochondrial physiology and the innate immune system. We screened several ginsenoside compounds showing antiviral activity using a robust HCV cell culture system. We investigated the role of ginsenosides in antiviral efficacy, alteration of the mitochondrial transmembrane potential, abnormal mitochondrial fission, its upstream signaling, and mitophagic process caused by HCV infection or DAA treatment. Only One of the compounds, ginsenoside Rg3 (G-Rg3), exhibited the notable and promising anti-HCV potential. Treatment of HCV-infected cells with G-Rg3 increased HCV core protein-mediated reduction in the expression level of cytosolic p21 required for increasing the cyclin-dependent kinase 1 (CDK1) activity, which catalyzes Ser616 phosphorylation of dynamin-related protein 1 (Drp1). The HCV-induced mitophagy, which follows mitochondrial fission, was also rescued by G-Rg3 treatment. CONCLUSIONS G-Rg3 inhibits HCV propagation. Its antiviral mechanism involves restoring the HCV-induced Drp1-mediated aberrant mitochondrial fission process, thereby resulting in suppression of persistent HCV infection.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg3 restores hepatitis C virus–induced aberrant mitochondrial dynamics and inhibits virus propagation

et al. 2017

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“…Some Chinese herbs, including Prunella vulgaris, L. Panaxginseng C.A. Meyer, Andrographis paniculata, Lentinus edodes and Spirulina platensis, display inhibitory effects on the entry step of various viruses, such as HIV-1, Hepatitis B and HSV-1 (Chang et al, 1991;Fiore et al, 2008;Harada, 2005;Hayashi et al, 1996aHayashi et al, , 1996bHayashi, 2008;Kang et al, 2013;Lee et al, 2014;Li et al, 2001;Liu et al, 2002;Sato et al, 1996;Seubsasana et al, 2011;Tabba et al, 1989;Yao et al, 1992;Yoshida et al, 1988;Zhang et al, 2007). However, whether these herbs could also have inhibitory activities against EBOV infection remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the inhibitory effect of an extract of Prunella vulgaris on Ebola virus glycoprotein (GP)-mediated virus entry and infection

Zhang

Bello

et al. 2016

Antiviral Research

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Currently, no approved antiviral therapeutic is available for treatment or prevention of Ebola virus (EBOV) infection. In this study, we characterized an EBOV-glycoprotein (GP) pseudotyped HIV-1-based vector system in different cell cultures, including human umbilical vein endothelial cells (HUVECs) and human macrophages, for the screening of anti-EBOV-GP agent(s). Based on this system, we demonstrated that an aqueous extract (CHPV) from the Chinese herb Prunella vulgaris displayed a potent inhibitory effect on EBOV-GP pseudotyped virus (EBOV-GP-V)-mediated infection in various cell lines, including HUVEC and macrophage. In addition, our results indicated that CHPV was able to block an eGFP-expressing Zaire ebola virus (eGFP-ZEBOV) infection in VeroE6 cells. The anti-EBOV activity of CHPV was exhibited in a dose-dependent manner. At a 12.5 μg/ml concentration, the CHPV showed a greater than 80% inhibition of EBOV-GP-V and eGFP-EBOV infections. Likewise, our studies suggested that the inhibitory effect of CHPV occurred by binding directly to EBOV-GP-Vs and blocking the early viral events. Interestingly, our results have shown that CHPV was able to enhance the anti-EBOV activity of the monoclonal antibody MAb 2G4 against EBOV-GP. Overall, this study provides evidence that CHPV has anti-EBOV activity and may be developed as a novel antiviral approach against EBOV infection.

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“…We concluded that H. pylori CagA plays a critical role in altering the FUT4 fucosylation by regulating the SP1 and HSF1 transcription. In promoter activity in liver cells [Kang et al, 2013]. Pan et al reported that Rg3 effectively downregulates transcription factors on the AQP1 promoter through p38…”

mentioning

confidence: 99%

Ginsenoside Rg3 induces FUT4-mediated apoptosis in H. pylori CagA-treated gastric cancer cells by regulating SP1 and HSF1 expressions

Aziz

Wang

Liu

et al. 2016

Toxicology in Vitro

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Stimulation of TRAF6/TAK1 degradation and inhibition of JNK/AP-1 signalling by ginsenoside Rg3 attenuates hepatitis B virus replication

Cited by 50 publications

References 32 publications

Ginsenoside Rg3 restores hepatitis C virus–induced aberrant mitochondrial dynamics and inhibits virus propagation

Ginsenoside Rg3 restores hepatitis C virus–induced aberrant mitochondrial dynamics and inhibits virus propagation

Characterization of the inhibitory effect of an extract of Prunella vulgaris on Ebola virus glycoprotein (GP)-mediated virus entry and infection

Ginsenoside Rg3 induces FUT4-mediated apoptosis in H. pylori CagA-treated gastric cancer cells by regulating SP1 and HSF1 expressions

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