Study Title:
Curcumin Protects Liver and Gallbladder
Study Abstract
Background and aim Chronic cholangiopathies have limited therapeutic options and represent an important indication for liver transplantation. Curcumin, the yellow pigment of the spice turmeric, has pleiotropic actions and attenuates hepatic damage in animal models of chemically-induced liver injury. Whether curcumin has beneficial effects in cholangiopathies is unknown.
Methods Potential anticholestatic, anti-inflammatory and antifibrotic mechanisms of curcumin were explored in vivo in Mdr2−/− mice as a murine model of chronic cholangiopathy; as well as in vitro in a cholangiocyte cell line (HuCCT1) and portal myofibroblasts (MFBs) isolated from Mdr2−/− mice.
Results Liver damage, cholestasis and fibrosis were reduced in Mdr2−/− mice after curcumin feeding. Moreover, curcumin inhibited cholangiocyte proliferation and expression of activation marker vascular cell adhesion molecule-1 in Mdr2−/− mice. Curcumin—similar to PPARγ synthetic agonist troglitazone—directly inhibited TNF-α-induced inflammatory activation of cholangiocytes in vitro, whereas these beneficial effects of curcumin were largely blocked by a PPARγ synthetic antagonist. In addition, curcumin blocked proliferation and activation of portal MFBs by inhibiting ERK1/2 phosphorylation, thus contributing to reduced fibrogenesis.
Conclusions These results show that curcumin may have multiple targets in liver including activation of PPARγ in cholangiocytes and inhibition of ERK1/2 signalling in MFBs, thereby modulating several central cellular events in a mouse model of cholangiopathy. Targeting these pathways may be a promising therapeutic approach to cholangiopathies.
From press release:
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.
Methods Potential anticholestatic, anti-inflammatory and antifibrotic mechanisms of curcumin were explored in vivo in Mdr2−/− mice as a murine model of chronic cholangiopathy; as well as in vitro in a cholangiocyte cell line (HuCCT1) and portal myofibroblasts (MFBs) isolated from Mdr2−/− mice.
Results Liver damage, cholestasis and fibrosis were reduced in Mdr2−/− mice after curcumin feeding. Moreover, curcumin inhibited cholangiocyte proliferation and expression of activation marker vascular cell adhesion molecule-1 in Mdr2−/− mice. Curcumin—similar to PPARγ synthetic agonist troglitazone—directly inhibited TNF-α-induced inflammatory activation of cholangiocytes in vitro, whereas these beneficial effects of curcumin were largely blocked by a PPARγ synthetic antagonist. In addition, curcumin blocked proliferation and activation of portal MFBs by inhibiting ERK1/2 phosphorylation, thus contributing to reduced fibrogenesis.
Conclusions These results show that curcumin may have multiple targets in liver including activation of PPARγ in cholangiocytes and inhibition of ERK1/2 signalling in MFBs, thereby modulating several central cellular events in a mouse model of cholangiopathy. Targeting these pathways may be a promising therapeutic approach to cholangiopathies.
From press release:
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.
Study Information
1.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 March
Laboratory of Experimental and Molecular Hepatology, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University Graz, Auenbruggerplatz 15, A-8036 Graz, Austria.