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Inhibition of T-cell inflammatory cytokines, hepatocyte NF-kappaB signaling, and HCV infection by standardized Silymarin.
Gastroenterology. 2007 May; 132(5):1925-36.G

Abstract

BACKGROUND & AIMS

Chronic hepatitis C is a serious global medical problem necessitating effective treatment. Because standard of care with pegylated interferon plus ribavirin therapy is costly, has significant side effects, and fails to cure about half of all infections, many patients seek complementary and alternative medicine to improve their health, such as Silymarin, derived from milk thistle (Silybum marianum). Milk thistle's clinical benefits for chronic hepatitis C are unsettled due to variability in standardization of the herbal product.

METHODS

In the current study, we focused on the anti-inflammatory and antiviral properties of a standardized Silymarin extract (MK-001).

RESULTS

MK-001 inhibited expression of tumor necrosis factor-alpha in anti-CD3 stimulated human peripheral blood mononuclear cells and nuclear factor kappa B-dependent transcription in human hepatoma Huh7 cells. Moreover, MK-001 dose dependently inhibited infection of Huh7 and Huh7.5.1 cells by JFH-1 virus. MK-001 displayed both prophylactic and therapeutic effects against HCV infection, and when combined with interferon-alpha, inhibited HCV replication more than interferon-alpha alone. Commercial preparations of Silymarin also displayed antiviral activity, although the effects were not as potent as MK-001. Antiviral effects of the extract were attributable in part to induction of Stat1 phosphorylation, while interferon-independent mechanisms were suggested when the extract was biochemically fractionated by high-performance liquid chromatography. Silybin A, silybin B, and isosilybin A, isosilybin B elicited the strongest anti-NF-kappaB and anti-HCV actions. These effects were independent of MK-001-induced cytotoxicity.

CONCLUSIONS

The data indicate that Silymarin exerts anti-inflammatory and antiviral effects, and suggest that complementary and alternative medicine-based approaches may assist in the management of patients with chronic hepatitis C.

Authors+Show Affiliations

Department of Laboratory Medicine, University of Washington, Seattle, Washington 98104-2499, USA. polyak@u.washington.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17484885

Citation

Polyak, Stephen J., et al. "Inhibition of T-cell Inflammatory Cytokines, Hepatocyte NF-kappaB Signaling, and HCV Infection By Standardized Silymarin." Gastroenterology, vol. 132, no. 5, 2007, pp. 1925-36.
Polyak SJ, Morishima C, Shuhart MC, et al. Inhibition of T-cell inflammatory cytokines, hepatocyte NF-kappaB signaling, and HCV infection by standardized Silymarin. Gastroenterology. 2007;132(5):1925-36.
Polyak, S. J., Morishima, C., Shuhart, M. C., Wang, C. C., Liu, Y., & Lee, D. Y. (2007). Inhibition of T-cell inflammatory cytokines, hepatocyte NF-kappaB signaling, and HCV infection by standardized Silymarin. Gastroenterology, 132(5), 1925-36.
Polyak SJ, et al. Inhibition of T-cell Inflammatory Cytokines, Hepatocyte NF-kappaB Signaling, and HCV Infection By Standardized Silymarin. Gastroenterology. 2007;132(5):1925-36. PubMed PMID: 17484885.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of T-cell inflammatory cytokines, hepatocyte NF-kappaB signaling, and HCV infection by standardized Silymarin. AU - Polyak,Stephen J, AU - Morishima,Chihiro, AU - Shuhart,Margaret C, AU - Wang,Chia C, AU - Liu,Yanze, AU - Lee,David Y-W, Y1 - 2007/02/21/ PY - 2006/11/07/received PY - 2007/02/08/accepted PY - 2007/5/9/pubmed PY - 2007/6/27/medline PY - 2007/5/9/entrez SP - 1925 EP - 36 JF - Gastroenterology JO - Gastroenterology VL - 132 IS - 5 N2 - BACKGROUND & AIMS: Chronic hepatitis C is a serious global medical problem necessitating effective treatment. Because standard of care with pegylated interferon plus ribavirin therapy is costly, has significant side effects, and fails to cure about half of all infections, many patients seek complementary and alternative medicine to improve their health, such as Silymarin, derived from milk thistle (Silybum marianum). Milk thistle's clinical benefits for chronic hepatitis C are unsettled due to variability in standardization of the herbal product. METHODS: In the current study, we focused on the anti-inflammatory and antiviral properties of a standardized Silymarin extract (MK-001). RESULTS: MK-001 inhibited expression of tumor necrosis factor-alpha in anti-CD3 stimulated human peripheral blood mononuclear cells and nuclear factor kappa B-dependent transcription in human hepatoma Huh7 cells. Moreover, MK-001 dose dependently inhibited infection of Huh7 and Huh7.5.1 cells by JFH-1 virus. MK-001 displayed both prophylactic and therapeutic effects against HCV infection, and when combined with interferon-alpha, inhibited HCV replication more than interferon-alpha alone. Commercial preparations of Silymarin also displayed antiviral activity, although the effects were not as potent as MK-001. Antiviral effects of the extract were attributable in part to induction of Stat1 phosphorylation, while interferon-independent mechanisms were suggested when the extract was biochemically fractionated by high-performance liquid chromatography. Silybin A, silybin B, and isosilybin A, isosilybin B elicited the strongest anti-NF-kappaB and anti-HCV actions. These effects were independent of MK-001-induced cytotoxicity. CONCLUSIONS: The data indicate that Silymarin exerts anti-inflammatory and antiviral effects, and suggest that complementary and alternative medicine-based approaches may assist in the management of patients with chronic hepatitis C. SN - 0016-5085 UR - https://www.unboundmedicine.com/medline/citation/17484885/Inhibition_of_T_cell_inflammatory_cytokines_hepatocyte_NF_kappaB_signaling_and_HCV_infection_by_standardized_Silymarin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(07)00395-2 DB - PRIME DP - Unbound Medicine ER -