Matt's Blog

Herbal Product Stevioside Inhibits HCV Replication and Curcumin Suppresses
Fibrogenic Cell Activity in Laboratory Studies
By Liz Highleyman
Given the suboptimal response rate and difficult side effects associated with
standard interferon-based therapy for chronic hepatitis C virus (HCV) infection,
many patients have used various alternative and complementary therapies, and
researchers have assessed several such agents in laboratory and clinical
studies.
At the Digestive Disease Week 2008 conference last month in San Diego,
researchers reported on 2 plant-derived therapies that may have the potential to
inhibit HCV and improve liver fibrosis.
Stevioside
In the first study, Kazuhisa Yuasa and colleagues assessed the in vitro anti-HCV
activity of stevioside, an agent derived from the leaves of the Stevia
rebaudiana plant that is used as a natural non-caloric sweetener.
Stevioside has been reported to have anti-inflammatory and antioxidant
properties, as well as an antiviral effect on rotavirus. According to background
information provided the investigators, some chronic hepatitis C patients who
regularly use stevioside have exhibited decreased HCV RNA or undetectable viral
load in the absence of interferon-based therapy.
In the present study, the researchers evaluated the antiviral effect of
stevioside on HCV replication using HCV replicon systems. They used ORN/C-5B/KE
cells supporting genome-length HCV RNA encoding the luciferase reporter gene,
and O cells replicating the genome-length HCV RNA in a real-time transcription
polymerase chain reaction analysis.
Both cell systems were exposed to several concentrations of sterilized
stevioside. The investigators assessed cytotoxicity, effect on signal
transduction pathways, and anti-HCV activity (with and without interferon).
Results
. A diluted solution of stevioside demonstrated no cytotoxicites to
either ORN/C-5B/KE cells or O cells.
. In both replicon systems, diluted stevioside suppressed HCV RNA in a
dose-dependent manner.
. A 1000 times diluted stevioside solution inhibited HCV replication by
about 30%.
. The same solution activated interferon-stimulated response element and
2-5A synthesizing enzyme gene promoter, but not the NF-kappa-?B gene promoter.
. Exposure to stevioside and interferon in combination produced an
additive, but not a synergistic antiviral effect.
"We showed [the] anti-HCV effect of stevioside and the additive anti-HCV effect
by combination of stevioside with interferon in vitro, and the activation of
interferon signal was considered as one of the mechanism[s]," the investigators
stated.
Thus, they concluded that, "stevioside is a possible antiviral agent for
hepatitis C virus infection," and they plan to conduct a pilot study of the
safety and efficacy of stevioside therapy for patients with chronic hepatitis C.
Curcumin
Looking at another herbal therapy, Anping Chen and colleagues presented 3
laboratory studies assessing at the effect of curcumin on hepatic stellate
cells.
Curcumin is the main component of the curry spice turmeric, derived from the
Curcuma longa plant. Prior research indicates that it has antioxidant,
anti-inflammatory, and anti-tumor properties. Hepatic stellate cells produce
extracellular matrix proteins such as collagen that are responsible for liver
fibrosis.
In the first study, the investigators found that curcumin promotes peroxisome
proliferator-activated receptor-gamma (PPAR-gamma) gene expression and
suppresses expression of the low-density lipoprotein (LDL) cholesterol receptor
gene, which in turn lowers the level of intracellular cholesterol and thereby
reduces the stimulatory effect of LDL on hepatic stellate cell activation.
In the second study, the researchers demonstrated that curcumin diminished the
activating effect of oxidized LDL on stellate cells by suppressing LOX-1 gene
expression, again via PPAR-gamma activation. Conversely, pre-treating the cells
with a PPAR-gamma antagonist (PD68235) eliminated the inhibitory effect of
curcumin.
Finally, the investigators showed that by increasing oxidative stress, insulin
stimulates hepatic stellate cell proliferation and collagen production. But
curcumin suppressed insulin-induced stellate cell activation by interrupting the
insulin signaling pathway and reducing oxidative stress, via the same PPAR-gamma
mechanism.
Hyperlipidemia (elevated blood lipid levels), obesity, and insulin resistance
are features of the metabolic syndrome, which is associated with liver steatosis
(accumulation of fat in hepatocytes). Steatosis is linked to fibrosis in
individuals with non-alcoholic fatty liver disease, as well as those with
chronic hepatitis C. Further, steatosis and insulin resistance are factors
associated with poor response to interferon-based anti-HCV therapy.
The results of these laboratory studies suggest that curcumin or related agents
that work by a similar mechanism might reduce fibrosis associated with
hyperlipidemia or insulin resistance in individuals with or without hepatitis C.
6/10/08
References
K Yuasa, K Sato, A Naganuma, and others. Stevioside as a possible antiviral
agent for hepatitis C virus infection. Digestive Disease Week (DDW) 2008. San
Diego, CA. May 17-22, 2008. Abstract S1943.
Q Kang and A Chen. Curcumin suppresses LDL receptor gene expression, leading to
the inhibition of cholesterol/LDL-induced hepatic stellate cell activation.
Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract
S1584.
Q Kang, A Chen, and JL Mehta. Curcumin inhibits ox-LDL-activated hepatic
stellate cells in vitro by suppressing gene expression of lectin-like
oxidized-LDL receptor via activation of peroxisome proliferator-activated
receptor-gamma. Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22,
2008. Abstract S1896.
J Lin and A Chen. Curcumin Suppresses Insulin-induced hepatic stellate cell
activation by interrupting insulin signaling and attenuating oxidative stress.
Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract
M1576.
http://www.hivandhepatitis.com:80/2008icr/ddw/docs/061008_b.html