Curcumin, a natural phytochemical from turmeric that is used as a spice in curry, holds promise in treating or preventing liver damage from an advanced form of a condition known as fatty liver disease, new Saint Louis University research suggests. Curcumin is contained in turmeric, a plant used by the Chinese to make traditional medicines for thousands of years. SLU's recent study highlights its potential in countering an increasingly common kind of fatty liver disease called non-alcoholic steatohepatitis (NASH). Linked to obesity and weight gain, NASH affects 3 to 4 percent of U.S. adults and can lead to a type of liver damage called liver fibrosis and possibly cirrhosis, liver cancer and death.
“My laboratory studies the molecular mechanism of liver fibrosis and is searching for natural ways to prevent and treat this liver damage,” said Anping Chen, Ph.D., corresponding author and director of research in the pathology department of Saint Louis University. The findings were published in the September 2010 issue of Endocrinology. “While research in an animal model and human clinical trials are needed, our study suggests that curcumin may be an effective therapy to treat and prevent liver fibrosis, which is associated with non-alcoholic steatohepatitis (NASH).”
High levels of blood leptin, glucose and insulin are commonly found in human patients with obesity and type 2 diabetes, which might contribute to NASH-associated liver fibrosis. Chen's most recent work tested the effect of curcumin on the role of high levels of leptin in causing liver fibrosis in vitro, or in a controlled lab setting. “Leptin plays a critical role in the development of liver fibrosis,” he said.
High levels of leptin activate hepatic stellate cells, which are the cells that cause overproduction of the collagen protein, a major feature of liver fibrosis. The researchers found that among other activities, curcumin eliminated the effects of leptin on activating hepatic stellate cells, which short-circuited the development of liver damage (Courtesy of EurekAlert!, a service of AAAS).
Reference: Youcai Tang, Anping Chen. Curcumin Protects Hepatic Stellate Cells against Leptin-Induced Activation in Vitro by Accumulating Intracellular Lipids. Endocrinology Vol. 151, No. 9 4168-4177 begin_of_the_skype_highlighting 9 4168-4177 end_of_the_skype_highlighting. doi:10.1210/en.2010-0191
The study was conducted in mice, some of which were fed a normal diet of rodent chow and some a 16-week diet of fructose and sucrose-enriched drinking water and trans-fat solids. Their liver tissue was then analyzed for fat content, scar tissue formation (fibrosis), and the biological mechanism of damage. This was done by measuring reactive oxygen stress, inflammatory cell type and plasma levels of oxidative stress markers, which are known to play important roles in the development of obesity-related liver disease and its progression to end-stage liver disease.
The investigators found that mice fed the normal calorie chow diet remained lean and did not have fatty liver disease. Mice fed high calorie diets (trans-fat alone or a combination of trans-fat and high fructose) became obese and had fatty liver disease.
“Interestingly, it was only the group fed the combination of trans-fat and high fructose which developed the advanced fatty liver disease which had fibrosis,” says Dr. Kohli. “This same group also had increased oxidative stress in the liver, increased inflammatory cells, and increased levels of plasma oxidative stress markers.”
Dr. Kohli hopes to further investigate the mechanism of liver injury caused by high fructose and sucrose enriched drinking water and study a therapeutic intervention of antioxidant supplementation. Antioxidants are natural defenses against oxidative stress and may reverse or protect against advanced liver damage, according to Dr. Kohli.
The investigators also would like to use this model to better understand human fatty liver disease and perform clinical trials using novel therapeutic and monitoring tools.
“Our data suggest that supplementation with pharmaceuticals agents should be tested on our new model to establish whether one is able to reverse or protect against progressive liver scarring and damage,” says Dr. Kohli.
The study was supported by grants from the National Institutes of Health and the Children's Digestive Health and Nutrition Foundation.
NAFLD is the most common cause of liver disease worldwide and research suggests the number of cases will climb given an increasing trend toward higher fat diets, obesity, decreased physical activity, and a rise in diabetes. Past studies indicate that more than 30 million Americans have NAFLD and approximately 8 million may have nonalcoholic steatohepatitis (NASH).
In the first study, Ramón Bataller, M.D., and colleagues from the Hospital Clínic in Barcelona, Spain investigated the effects of cigarette smoking (CS) in obese rats. Rats were divided into 4 groups (n=12 per group): obese smokers, obese non-smokers, control smokers and control non-smokers. Smoker rats were exposed to 2 cigarettes/day, 5 days/week for 4 weeks. Researchers found that obese rats exposed to CS showed a significant increase in ALT serum levels (indicating liver disease), while this effect was not observed in control rats.
“Our results show that CS causes oxidative stress and worsens the severity of NAFLD in obese rats,” said Dr. Bataller. “Further studies should investigate longer exposures to CS, and assess whether this finding also occurs in patients with obesity and NAFLD.”
In her editorial, also published in Hepatology this month, Claudia Zein, M.D., from the Cleveland Clinic, noted that “the importance of these results is that taken together with other experimental and clinical data, they support that cigarette smoking appears to aggravate liver injury in patients with liver disease.” Dr. Zein added, “Studies characterizing the effects of cigarette smoking in human NAFLD will be crucial because of the vast number of patients that may benefit from modification of this risk factor.”
Additionally, prior studies suggest an over consumption of high fructose corn syrup (HFCS), primarily in the form of soft-drinks, have contributed to weight gain and the rise in obesity, particularly in children and adolescents. Table sugar (sucrose) and HFCS are the two major dietary sources of fructose. Over the past 40 years, consumption of dietary fructose has increased 1,000% according to Bray et al, and doctors believe it to be a major cause of NAFLD.
Researchers from Duke University studied 341 adults enrolled in the NASH Clinical Research Network who responded to a Block food questionnaire within 3 months of a liver biopsy. Fructose consumption was estimated conservatively by including that found in beverages, which accounts for 50% of dietary fructose intake. Results showed that 27.9% of participants consumed at least 1 fructose-containing beverage per day, 52.5% had 1 to 6 beverages with fructose per week, and 19.7% drank no beverages with fructose.
“In patients with NAFLD, daily fructose ingestion was associated with reduced fatty liver (steatosis), but we found increased fibrosis,” noted Manal Abdelmalek, M.D., M.P.H, and lead author of the study. “Further dietary intervention studies are needed to evaluate whether a low-fructose diet improves metabolic disturbances associated with NAFLD and improves patient outcomes for those at risk of disease progression,” concluded Dr. Abdelmalek.
A second fructose study led by Ling-Dong Kong, M.D., from Nanjing University in China investigated the effects of curcumin on fructose-induced hypertriglyceridemia and fatty liver in rats. Curcumin, a compound derived from turmeric (curcuma root), is sold as an herbal supplement and is believed to have anti-inflammatory, anti-tumor, and anti-viral properties. Researchers observed a hyperactivity of hepatic protein tyrosine phosphatase 1B (PTP1B), which is associated with defective insulin and leptin signaling, in fructose-fed rats.
For the first time this study demonstrated that curcumin inhibited hepatic PTP1B expression and activity in fructose-fed rats. “Our results provide novel insights into the potential therapeutic mechanisms of curcumin on fructose-induced hepatic steatosis associated with insulin and leptin resistance,” said Dr. Kong.
These studies indicate modifying risks such as smoking and fructose consumption offer potential benefits for those with liver diseases. Further studies are needed to explore these benefits in preventing the progression of liver disease.
Curcumin, one of the principal components of the Indian spice turmeric, seems to delay the liver damage that eventually causes cirrhosis, suggests preliminary experimental research in the journal Gut. Curcumin, which gives turmeric its bright yellow pigment, has long been used in Indian Ayurvedic medicine to treat a wide range of gastrointestinal disorders.
Previous research has indicated that it has anti-inflammatory and antioxidant properties which may be helpful in combating disease. The research team wanted to find out if curcumin could delay the damage caused by progressive inflammatory conditions of the liver, including primary sclerosing cholangitis and primary biliary cirrhosis.
Both of these conditions, which can be sparked by genetic faults or autoimmune disease, cause the liver's plumbing system of bile ducts to become inflamed, scarred, and blocked. This leads to extensive tissue damage and irreversible and ultimately fatal liver cirrhosis.
The research team analysed tissue and blood samples from mice with chronic liver inflammation before and after adding curcumin to their diet for a period of four and a period of eight weeks.
The results were compared with the equivalent samples from mice with the same condition, but not fed curcumin.
The findings showed that the curcumin diet significantly reduced bile duct blockage and curbed liver cell (hepatocyte) damage and scarring (fibrosis) by interfering with several chemical signalling pathways involved in the inflammatory process.
These effects were clear at both four and eight weeks. No such effects were seen in mice fed a normal diet.
The authors point out that current treatment for inflammatory liver disease involves ursodeoxycholic acid, the long term effects of which remain unclear. The other alternative is a liver transplant.
Curcumin is a natural product, they say, which seems to target several different parts of the inflammatory process, and as such, may therefore offer a very promising treatment in the future.
Source: Anna Baghdasaryan, Thierry Claudel, Astrid Kosters, Judith Gumhold, Dagmar Silbert, Andrea Thüringer, Katharina Leski, Peter Fickert, Saul J Karpen, Michael Trauner. Curcumin improves sclerosing cholangitis in Mdr2-/- mice by inhibition of cholangiocyte inflammatory response and portal myofibroblast proliferation. Gut, 2010; 59: 521-530