Legalon-SIL downregulates HCV core and NS5A in human hepatocytes expressing full-length HCV

Mehrab-Mohseni, Marjan; Sendi, Hossein; Steuerwald, Nury; Ghosh, Sriparna; Schrum, Laura W.; Bonkovsky, Herbert L.

doi:10.3748/wjg.v17.i13.1694

Cited by 18 publications

(14 citation statements)

References 27 publications

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“…They reported that increased expression of HO-1 is associated with diminished HCV replication and also with an increase of the resistance of hepatocytes to oxidative damage. Based on this findings, heme oxygenase regulation could be useful as an adjunctive antiviral therapy [62][63][64] .…”

Section: Heme Oxygenase Regulationmentioning

confidence: 88%

“…On the other hand, HCV is potentially lymphotropic, because it can invade and propagate in cells of the [47,48] 400-544 IU/d or 600 mg 1 Vitamin C [48] 500 mg-10 g N-acetylcysteine [78] 600 mg or 1800 mg/d 1 Mitoquine Q [65,66] 40 or 80 mg/d α-tocopherol [79] 600 mg, 500 mg/d, 800 IU/d Glycyrrhizin [40,42,53,54] 500 mg, 120 mg Different mechanisms Silymarin (Silibinin A, Silibinin B, etc.) [40,64,[80][81][82] 250 mg or 5-20 mg/kg 1 S-adenosylmethionine [69] 1600 mg/d 1 Acetylsalicylic acid [73] 4 mmol/L (in vitro) Gallic acid 300 mg/mL (in vitro) 1 Combined treatment with interferon.…”

Section: Antioxidant Therapymentioning

confidence: 99%

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Oxidative stress modulation in hepatitis C virus infected cells

Lozano-Sepúlveda

Bryan-Marrugo

Córdova-Fletes

et al. 2015

WJH

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Section: Heme Oxygenase Regulationmentioning

confidence: 88%

Section: Antioxidant Therapymentioning

confidence: 99%

Oxidative stress modulation in hepatitis C virus infected cells

Lozano-Sepúlveda

Bryan-Marrugo

Córdova-Fletes

et al. 2015

WJH

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“…Finally, the antiviral action of silybin against HCV replication is also related to its antioxidant properties. In fact, silybin reduces the levels of some free radical species produced during HCV gene expression, and in this manner it interferes with the regulation of some proteins of the HCV core (for example, downregulation of HMOX-1 mRNA and upregulation of Nrf2 protein) necessary for HCV replication [59].…”

Section: Discussionmentioning

confidence: 99%

Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: A randomized controlled trial

Loguercio

Andreone

Brisc

et al. 2012

Free Radical Biology and Medicine

214

147

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The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with Free

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“…HO-1 over-expression has been observed to decrease HCV replication, reduce pro-oxidant production in replicon cells, and increase resistance to oxidative injury [52] . These findings strongly suggest potential therapeutic roles for HO-1 [53] .…”

Section: Ho-1 As a Potential Therapeutic Target In Liver Diseasesmentioning

confidence: 99%

Cytoprotective role of heme oxygenase-1 and heme degradation derived end products in liver injury

Origassa¹,

Câmara²

2013

WJH

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The activation of heme oxygenase-1 (HO-1) appears to be an endogenous defensive mechanism used by cells to reduce inflammation and tissue damage in a number of injury models. HO-1, a stress-responsive enzyme that catabolizes heme into carbon monoxide (CO), biliverdin and iron, has previously been shown to protect grafts from ischemia/reperfusion and rejection. In addition, the products of the HO-catalyzed reaction, particularly CO and biliverdin/bilirubin, have been shown to exert protective effects in the liver against a number of stimuli, as in chronic hepatitis C and in transplanted liver grafts. Furthermore, the induction of HO-1 expression can protect the liver against damage caused by a number of chemical compounds. More specifically, the CO derived from HO-1-mediated heme catabolism has been shown to be involved in the regulation of inflammation; furthermore, administration of REVIEW 541October 27, 2013|Volume 5|Issue 10| WJH|www.wjgnet.com low concentrations of exogenous CO has a protective effect against inflammation. Both murine and human HO-1 deficiencies have systemic manifestations associated with iron metabolism, such as hepatic overload (with signs of a chronic hepatitis) and iron deficiency anemia (with paradoxical increased levels of ferritin). Hypoxia induces HO-1 expression in multiple rodent, bovine and monkey cell lines, but interestingly, hypoxia represses expression of the human HO-1 gene in a variety of human cell types (endothelial cells, epithelial cells, T cells). These data suggest that HO-1 and CO are promising novel therapeutic molecules for patients with inflammatory diseases. In this review, we present what is currently known regarding the role of HO-1 in liver injuries and in particular, we focus on the implications of targeted induction of HO-1 as a potential therapeutic strategy to protect the liver against chemically induced injury.

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Legalon-SIL downregulates HCV core and NS5A in human hepatocytes expressing full-length HCV

Abstract: Our results demonstrate that treatment with LS downregulates HCV core and NS5A expression in CON1 cells which express full length HCV genotype 1b, and suggests that LS may prove to be a valuable alternative or adjunctive therapy for the treatment of HCV infection.

Cited by 18 publications

References 27 publications

Oxidative stress modulation in hepatitis C virus infected cells

Oxidative stress modulation in hepatitis C virus infected cells

Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: A randomized controlled trial

Cytoprotective role of heme oxygenase-1 and heme degradation derived end products in liver injury

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