Orlean's Post Regarding Stevioside/Curcumin Study
by Marcia2202, Jun 30, 2008



Herbal Product Stevioside Inhibits HCV Replication and Curcumin Suppresses Fibrogenic Cell Activity in Laboratory Studies
Last updated:26June2008

By Liz Highleyman hivandhepatitis.com

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.

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).

• 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.

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.

Related Discussions
Member Comments (24)
by Marcia2202, Jun 30, 2008
I would like to ask if you know how, when and how much stevia and curcumin should be taken.

by comeagain, Jun 30, 2008
I googled curcumin very interesting subject I will investigate furhter in it.
It seemed to be helpful for enlarged heart condition which my mother has and also could be helful for cancer forms like prostata which my father who is gonna be 80 in mars have, and my grandfather died of at 76 years of age.

I also read in a swedish site that together with blackpepper it would be even more effectiv.

You can bye it in capsels , they recomended different doses for healthy normal people and a lot higher doses if you have a liver or a cancer disease. there was a warning about eating it without food and at all  if you have some stoomick problems.
I wont write the doses down since the companies who sells it are no doctors.

by it'sallgood, Jun 30, 2008

Background and Aim: Curcumin, the major polyphenolic compound in turmeric, has been shown to attenuate hepatic damage in several animal models of liver injury. The aim of the present study was to examine the efficacy of curcumin in preventing thioacetamide-induced cirrhosis and to unravel the mechanism of curcumin's effect on hepatic fibrosis in rats.

Methods: Liver cirrhosis was induced by thioacetamide (TAA; 200 mg/kg, i.p.) twice weekly for 12 weeks. One group of rats concomitantly received curcumin (300 mg/kg/day, by gavage for 12 weeks); the control group received the solvent at identical amounts and duration.

Results: TAA administration induced liver cirrhosis, which was inhibited by curcumin. Liver histopathology, hydroxyproline levels and spleen weights were significantly lower in the rats treated with TAA+curcumin compared with TAA only (P<0.001). Immunohistochemical studies and in situ hybridization demonstrated inhibition of hepatic stellate cell (α smooth muscle actin-positive) activation and collagen αI (I) gene expression in the livers of the TAA+curcumin-treated rats. Curcumin reduced oxidative stress as shown by the decreased hepatic nitrotyrosine staining in the curcumin+TAA-treated rats. Curcumin treatment had no effect on pre existing liver cirrhosis. As determined by in vitro studies using the rat HSC-T6 cell line, curcumin had no direct inhibitory effect on collagen α1 (I) messenger RNA expression. Further studies in these cells using reverse transcriptase-polymerase chain reaction demonstrated that curcumin had no effect on the expression of PDGF-induced TIMP-1 and TIMP-2, TGFβ1, TGFβ2 and MCP-1 but significantly inhibited tumor necrosis factor alpha expression. Curcumin had no effect on hepatic stellate cells proliferation. Zymography showed that curcumin had no effect on matrix metalloproteinase-2 activity.

Conclusions: Curcumin inhibited the development of TAA-induced liver cirrhosis mainly due to its anti-inflammatory activities and not by a direct anti-fibrotic effect. As curcumin ingestion is safe in humans, it may be reasonable to assess in clinical studies the beneficial effect of curcumin in slowing the development of liver cirrhosis.

Rafael Bruck, Michal Ashkenazi, Sigal Weiss, Ilana Goldiner, Haim Shapiro, Hussein Aeed, Olga Genina, Zamir Helpern, Mark Pines (2007) Prevention of liver cirrhosis in rats by curcumin
Liver International 27 (3) , 373–383 doi:10.1111/j.1478-3231.2007.01453.x
by it'sallgood, Jun 30, 2008
here is the curcumin thread,


by justme53, Jun 30, 2008
I  would also like to know what the therapeutic levels are for both Stevia and Curcumin. Perhaps it's too early for these studies to apply their findings "across the board".

My bottle of stevia extract (pure/alcohol free) says up to 15 drops per day in three doses of 5 drops each ( or 25 mg per) for "general usage". I take a Curcumin supp of 900 mg. per day in three doses of 300 mg, working up to a higher dosage as per Gauf's regimen as tolerated. So far, so good....

Just for the record, I believe that many of these supplements hold promise not only as possible complementary tx additives, but as pre/post possibilites as well.
by medicmommy, Jun 30, 2008
Thanks for that! The first post got a bit buried in some of our passionate responses...LOL  this is some good info...
by Marcia2202, Jul 01, 2008
Thank you for the thanks, for reposting the post. :-)

The one we really need to thank is orleans and I hope he will chime in with more info on this, despite we ended up totally trashing his original thread.


by Marcia2202, Jul 01, 2008
I have the Stevia Leaf Liquid Concentrate (dark liquid made from whole stevia leaves in a base of purified water) It says to use 5 drops in beverages or in cooking as desired.

1 serving corresponds to 0.14 ml*     *daily value not established.

I totally agree with the pre and post tx possibilities. Actually I am more cautious about how to use them on tx, due to drug herb interactions. But that should at least not be a concern with stevia.

I wonder how we can find out what the 'medicinal' dosage of stevia should be.

by orleans, Jul 01, 2008
Hey, I just ran across this report and do not really know anything else about these substances. Thought it might gererate some intrest and maybe some info. Sorry, jerry