Basic–liver, pancreas, and biliary tractInhibition of T-Cell Inflammatory Cytokines, Hepatocyte NF-κB Signaling, and HCV Infection by Standardized Silymarin
Section snippets
Patients
Overall, 3 of the 6 subjects were male, and the median age was 42.5 years (range, 37–52). Four of 6 subjects were HCV-infected (all genotype 1, median HCV RNA level 11,891,922 IU/mL (range, 402,708–46,573,010). Liver biopsy data were available on 3 HCV-infected subjects. The necroinflammatory activity (grade) and degree of fibrosis (stage) of the liver disease were scored semiquantitatively, each on a scale of 0–4, using the Batts and Ludwig method.42 All had at least grade 1 inflammation.
MK-001: A Standardized Extract of Silymarin
Biologic authentication of milk thistle is based on macroscopic and microscopic examinations of the plant by light and electronic microscopy, followed by chemical authentication by high-performance liquid chromatograph and/or liquid chromatograph-mass spectrometry fingerprinting. Using these methods, a standardized preparation of Silymarin, called MK-001, was recently developed.22 MK-001 contains the highest content (92%) of flavonolignans and every component (>2%) in MK-001 has been completely
Discussion
Despite global use, the detailed molecular mechanisms of Silymarin-induced hepatoprotection are not known. In the current report, we show for the first time that a rigorously standardized Silymarin (MK-001) displayed anti-inflammatory actions via inhibition of NF-κB induced transcription in human liver cell cultures, inhibition of inflammatory cytokine induction in human PBMC, and direct antiviral effects against HCV infection. Thus, our data are in accord with the view that Silymarin is
References (91)
Liver transplantation for hepatitis C: the promise and the challenge
Hepatology
(1995)- et al.
Projecting future complications of chronic hepatitis C in the United States
Liver Transplant
(2003) - et al.
A multicenter, randomized trial of daily high-dose interferon-alfa 2b for the treatment of chronic hepatitis C: pretreatment stratification by viral burden and genotype
Am J Gastroenterol
(2000) - et al.
Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial
Lancet
(2001) - et al.
Use of herbal supplements for chronic liver disease
Clin Gastroenterol Hepatol
(2004) - et al.
Mechanisms and preclinical efficacy of silibinin in preventing skin cancer
Eur J Cancer
(2005) Toxic heavy metals and undeclared drugs in Asian herbal medicines
Trends Pharmacol Sci
(2002)- et al.
Efficient replication of the genotype 2a hepatitis C virus subgenomic replicon
Gastroenterology
(2003) - et al.
Biomedicines to reduce inflammation but not viral load in chronic HCV—what’s the sense?
Trends Biotechnol
(2004) - et al.
What is disrupting IFN-alpha’s antiviral activity?
Trends Biotechnol
(2004)
Oxidative stress during viral infection: a review
Free Radic Biol Med
Moderate alcohol consumption increases oxidative stress in patients with chronic hepatitis C
Hepatology
Association of hepatitis virus infection, alcohol consumption and plasma vitamin A levels with urinary 8-hydroxydeoxyguanosine in chemical workers
Mutat Res
Hepatitis C virus proteins: direct link to hepatic oxidative stress, steatosis, carcinogenesis and more
Gastroenterology
Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein
Gastroenterology
Nonstructural 3 protein of hepatitis C virus triggers an oxidative burst in human monocytes via activation of NADPH oxidase
J Biol Chem
Superoxide dismutase in patients with chronic hepatitis C virus infection
Free Radic Biol Med
Molecular pathogenesis of human hepatocellular carcinoma
Toxicology
Oxidative DNA damage: assessment of the role in carcinogenesis, atherosclerosis, and acquired immunodeficiency syndrome
Free Radic Biol Med
Inhibitors of cytokine signal transduction
J Biol Chem
The p38 mitogen-activated protein kinase pathway and its role in interferon signaling
Pharmacol Ther
Primary cultures of human hepatocytes as a tool in cytotoxicity studies: cell protection against model toxins by flavonolignans obtained from Silybum marianum
Toxicol Lett
Medicinal herbs for hepatitis C virus infection: a Cochrane hepatobiliary systematic review of randomized trials
Am J Gastroenterol
Milk thistle for the treatment of liver disease: a systematic review and meta-analysis
Am J Med
Two-year results of a randomised double-blinded trial evaluating silymarin for chronic hepatitis C
Dig Liver Dis
Randomised double-blinded trial evaluating silymarin for chronic hepatitis C in an Egyptian village: study description and 12-month results
Dig Liver Dis
Hepatitis C viral infection in liver transplant recipients
Hepatology
Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection
N Engl J Med
Milk thistle
Am Fam Physician
Silymarin treatment of viral hepatitis: a systematic review
J Viral Hepat
Herbal medicines for liver diseases
Dig Dis Sci
Prostate cancer chemoprevention by silibinin: Bench to bedside
Mol Carcinog
Silibinin strongly inhibits growth and survival of human endothelial cells via cell cycle arrest and downregulation of survivin, Akt and NF-kappaB: implications for angioprevention and antiangiogenic therapy
Oncogene
Oral silibinin inhibits lung tumor growth in athymic nude mice and forms a novel chemocombination with doxorubicin targeting nuclear factor kappaB-mediated inducible chemoresistance
Clin Cancer Res
Integration of herbal medicine into modern medical practices: issues and prospects
Integr Cancer Ther
Herbal medicine: from the past to the future
Public Health Nutr
Maternal use of ginseng and neonatal androgenization
JAMA
Heavy metals in traditional Indian remedies
Eur J Clin Pharmacol
Chromium in some herbal drugs
Bull Environ Contam Toxicol
Molecular structure and stereochemistry of silybin A, silybin B, isosilybin A, and isosilybin B, isolated from Silybum marianum (milk thistle)
J Nat Prod
Standardization of Silymarin (MK-001), a popular seed extract of Silybum marianum (milk thistle) for liver protection
J Agric Food Chem
Unravelling hepatitis C virus replication from genome to function
Nature
Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line
Science
Efficient initiation of HCV RNA replication in cell culture
Science
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2022, PhytomedicineCitation Excerpt :It is also worth mentioning that GL exert a synergistic effect with interferon alpha (IFN-α) which reduced the replication of HCV. Briefly, incubation of a variable concentration of GL (14 ± 2 μg) with IFN-α for 24 h in Huh-7 cells inoculated with 2 × 105 HCV reduced 95% of the viral titer compared to GL alone (55%) (Polyak et al., 2007). Furthermore, GL was found to inhibit the replication, adsorption, and penetration of SARS-associated coronavirus (SARS-CoV), without inducing cytotoxic effect to the host cells (Cinatl et al., 2003).
Molecular docking, ADMET analysis, and bioactivity studies of phytochemicals from Phyllanthus niruri as potential inhibitors of hepatitis C virus NSB5 polymerase
2022, Journal of the Indian Chemical SocietyCitation Excerpt :As reported by Calland and his co-workers [7], bioactive compounds from plants displayed noticeable activities as anti-HCV agents when tested using in vivo and cellular models. Silymarin/Silibinin an important flavonoid extracted from (Silybum marianum) has been reported as an inhibitor of HCV replication in cell culture [8] and possessed hepatoprotective effects through their immunomodulatory and anti-inflammatory activities [9]. ( −)-Epigallocatechin-3-gallate (EGCG), extracted from (Camellia sinensis) has been observed to prevent HCV entry [10–12].
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The authors of this study have no conflicts of interest to disclose.
- 1
D. Y. W.–L. is supported in part by NIH-STTR grant (R42-AT-00766) to Natural Pharmacia International Inc.
- 2
S. J. P. is partially supported by NIH Grants R01 DK 62187 and U19 AI 66328 from NIDDK and NIAID, respectively.