Herbal Product Stevioside Inhibits HCV Replication and Curcumin Suppresses Fibrogenic Cell Activity in Laboratory Studies
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
"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. 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.
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