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Aqueous extract of the edible Gracilaria tenuistipitata inhibits hepatitis C viral replication via cyclooxygenase-2 suppression and reduces virus-induced inflammation.

Chen KJ, Tseng CK, Chang FR, Yang JI, Yeh CC, Chen WC, Wu SF, Chang HW, Lee JC - PLoS ONE (2013)

Bottom Line: AEGT synergistically enhanced interferon-α (IFN-α) anti-HCV activity in a combination treatment.We found that AEGT also significantly suppressed virus-induced cyclooxygenase-2 (COX-2) expression at promoter transactivation and protein levels.Notably, addition of exogenous COX-2 expression in AEGT-treated HCV replicon cells gradually abolished AEGT anti-HCV activity, suggesting that COX-2 down-regulation was responsible for AEGT antiviral effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.

ABSTRACT
Hepatitis C virus (HCV) is an important human pathogen leading to hepatocellular carcinoma. Using an in vitro cell-based HCV replicon and JFH-1 infection system, we demonstrated that an aqueous extract of the seaweed Gracilaria tenuistipitata (AEGT) concentration-dependently inhibited HCV replication at nontoxic concentrations. AEGT synergistically enhanced interferon-α (IFN-α) anti-HCV activity in a combination treatment. We found that AEGT also significantly suppressed virus-induced cyclooxygenase-2 (COX-2) expression at promoter transactivation and protein levels. Notably, addition of exogenous COX-2 expression in AEGT-treated HCV replicon cells gradually abolished AEGT anti-HCV activity, suggesting that COX-2 down-regulation was responsible for AEGT antiviral effects. Furthermore, we highlighted the inhibitory effect of AEGT in HCV-induced pro-inflammatory gene expression such as the expression of tumour necrosis factor-α, interleukin-1β, inducible nitrite oxide synthase and COX-2 in a concentration-dependent manner to evaluate the potential therapeutic supplement in the management of patients with chronic HCV infections.

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AEGT suppression of HCV-induced or NS5A-induced pro-inflammatory gene expression.HCV JFH-1-infected or pCMV-NS5A-Myc-transfected Huh-7 cells were incubated with indicated AEGT concentrations for 3 days. RNA levels of (A and E) TNF-α, (B and F) IL-1β, (C and G) iNOS and (D and H) COX-2 in each experiment were determined by qRT-PCR. The relative RNA level of each gene was normalized with cellular gapdh mRNA. Non-infected or non-transfected Huh-7 cells served as the basal control, which is defined as 1. Each value was represented as the mean ± SD of three independent experiments. *P<0.05; **P<0.01.
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pone-0057704-g005: AEGT suppression of HCV-induced or NS5A-induced pro-inflammatory gene expression.HCV JFH-1-infected or pCMV-NS5A-Myc-transfected Huh-7 cells were incubated with indicated AEGT concentrations for 3 days. RNA levels of (A and E) TNF-α, (B and F) IL-1β, (C and G) iNOS and (D and H) COX-2 in each experiment were determined by qRT-PCR. The relative RNA level of each gene was normalized with cellular gapdh mRNA. Non-infected or non-transfected Huh-7 cells served as the basal control, which is defined as 1. Each value was represented as the mean ± SD of three independent experiments. *P<0.05; **P<0.01.

Mentions: Chronic inflammation caused by HCV infection is considered as one of the major pathogenic mechanisms, A number of pro-inflammatory gene products as well cytokines, including COX-2, iNOS, TNF-α and IL-1β, are believed to play a critical role in inflammatory diseases [36], [37]. To examine the potential AEGT hepatoprotective actions against the HCV-stimulated inflammatory mediators described above, HCV JFH-1-infected Huh-7 cells were treated with different concentrations of AEGT for 3 days. qRT-PCR analysis demonstrated that compared to the uninfected cells, the elevated mRNA levels of these induced pro-inflammatory mediators were reduced in a concentration-dependent manner by AEGT (Fig. 5A–D). Among HCV proteins, NS5A is one of risk factors involving hepatocarcinogenesis through chronic inflammation [38], [39]. To further investigate the potential AEGT hepatoprotective actions against the NS5A-stimulated inflammatory mediators, NS5A-transfected Huh-7 cells were treated with different concentrations of AEGT for 3 days. Similar results for the reduction of NS5A-induced pro-inflammatory mediators by AEGT treatment were observed compared with the untreated cells (Fig. 5E–H).


Aqueous extract of the edible Gracilaria tenuistipitata inhibits hepatitis C viral replication via cyclooxygenase-2 suppression and reduces virus-induced inflammation.

Chen KJ, Tseng CK, Chang FR, Yang JI, Yeh CC, Chen WC, Wu SF, Chang HW, Lee JC - PLoS ONE (2013)

AEGT suppression of HCV-induced or NS5A-induced pro-inflammatory gene expression.HCV JFH-1-infected or pCMV-NS5A-Myc-transfected Huh-7 cells were incubated with indicated AEGT concentrations for 3 days. RNA levels of (A and E) TNF-α, (B and F) IL-1β, (C and G) iNOS and (D and H) COX-2 in each experiment were determined by qRT-PCR. The relative RNA level of each gene was normalized with cellular gapdh mRNA. Non-infected or non-transfected Huh-7 cells served as the basal control, which is defined as 1. Each value was represented as the mean ± SD of three independent experiments. *P<0.05; **P<0.01.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585194&req=5

pone-0057704-g005: AEGT suppression of HCV-induced or NS5A-induced pro-inflammatory gene expression.HCV JFH-1-infected or pCMV-NS5A-Myc-transfected Huh-7 cells were incubated with indicated AEGT concentrations for 3 days. RNA levels of (A and E) TNF-α, (B and F) IL-1β, (C and G) iNOS and (D and H) COX-2 in each experiment were determined by qRT-PCR. The relative RNA level of each gene was normalized with cellular gapdh mRNA. Non-infected or non-transfected Huh-7 cells served as the basal control, which is defined as 1. Each value was represented as the mean ± SD of three independent experiments. *P<0.05; **P<0.01.
Mentions: Chronic inflammation caused by HCV infection is considered as one of the major pathogenic mechanisms, A number of pro-inflammatory gene products as well cytokines, including COX-2, iNOS, TNF-α and IL-1β, are believed to play a critical role in inflammatory diseases [36], [37]. To examine the potential AEGT hepatoprotective actions against the HCV-stimulated inflammatory mediators described above, HCV JFH-1-infected Huh-7 cells were treated with different concentrations of AEGT for 3 days. qRT-PCR analysis demonstrated that compared to the uninfected cells, the elevated mRNA levels of these induced pro-inflammatory mediators were reduced in a concentration-dependent manner by AEGT (Fig. 5A–D). Among HCV proteins, NS5A is one of risk factors involving hepatocarcinogenesis through chronic inflammation [38], [39]. To further investigate the potential AEGT hepatoprotective actions against the NS5A-stimulated inflammatory mediators, NS5A-transfected Huh-7 cells were treated with different concentrations of AEGT for 3 days. Similar results for the reduction of NS5A-induced pro-inflammatory mediators by AEGT treatment were observed compared with the untreated cells (Fig. 5E–H).

Bottom Line: AEGT synergistically enhanced interferon-α (IFN-α) anti-HCV activity in a combination treatment.We found that AEGT also significantly suppressed virus-induced cyclooxygenase-2 (COX-2) expression at promoter transactivation and protein levels.Notably, addition of exogenous COX-2 expression in AEGT-treated HCV replicon cells gradually abolished AEGT anti-HCV activity, suggesting that COX-2 down-regulation was responsible for AEGT antiviral effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan.

ABSTRACT
Hepatitis C virus (HCV) is an important human pathogen leading to hepatocellular carcinoma. Using an in vitro cell-based HCV replicon and JFH-1 infection system, we demonstrated that an aqueous extract of the seaweed Gracilaria tenuistipitata (AEGT) concentration-dependently inhibited HCV replication at nontoxic concentrations. AEGT synergistically enhanced interferon-α (IFN-α) anti-HCV activity in a combination treatment. We found that AEGT also significantly suppressed virus-induced cyclooxygenase-2 (COX-2) expression at promoter transactivation and protein levels. Notably, addition of exogenous COX-2 expression in AEGT-treated HCV replicon cells gradually abolished AEGT anti-HCV activity, suggesting that COX-2 down-regulation was responsible for AEGT antiviral effects. Furthermore, we highlighted the inhibitory effect of AEGT in HCV-induced pro-inflammatory gene expression such as the expression of tumour necrosis factor-α, interleukin-1β, inducible nitrite oxide synthase and COX-2 in a concentration-dependent manner to evaluate the potential therapeutic supplement in the management of patients with chronic HCV infections.

Show MeSH
Related in: MedlinePlus