Indian Spice May Prevent Liver Damage [if: for my fellow curcumin users] By Chris Emery, Contributing Writer, MedPage Today Published: March 24, 2010 Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Action Points * Explain to interested patients that this study shows that curcumin appears to delay liver damage in mice. It has not been evaluated for this purpose in humans. * Note that investigators believe curcumin might be pursued as a treatment for chronic cholangiopathies in humans. A major component of the Indian spice turmeric was found to decrease inflammation and fibrosis in vitro and in an animal model of chronic cholangiopathy, a new study found. Mdr2-/- mice fed curcumin, the compound that gives turmeric its bright yellow color, had reduced liver damage, cholestasis, and fibrosis compared with mice fed a normal diet (P<0.05 for each), according to an online report in the March 23 issue of Gut. "We demonstrate that curcumin is beneficial in a genetic mouse model of cholangiopathy and biliary fibrosis, and propose potential molecular and cellular targets of curcumin in this model," Michael Trauner, MD, of Medical University Graz in Austria, and colleagues wrote. "Collectively, our findings have important implications for understanding the pathophysiology of cholangiopathies and suggest that combined targeting of cholangiocyte and portal myofibroblasts activation could represent a central strategy to treat or delay the progression of chronic cholangiopathies and liver fibrosis." Progressive inflammatory conditions of the liver include primary sclerosing cholangitis and primary biliary cirrhosis, which are characterized by inflammation, scarring, and destruction of the bile ducts inside and outside of the liver. Chronic cholangiopathies, which are usually genetic or autoimmune in origin, cause inflammation and fibrosis and can lead to the need for liver transplantation. Previous research in rodents with chemically induced liver damage and fibrosis found that curcumin has anti-inflammatory, antioxidative, and antifibrotic properties, the investigators noted. The compound comes from the rhizomes of the perennial herb Curcuma longa and has been used for centuries in Ayurvedic medicine to treat a wide range of gastrointestinal disorders. But recent research suggests the chemical might have other medical applications, including possible effects on plaque in Alzheimer's disease. In the current liver study, investigators noted, it was unknown if curcumin could prevent bile duct inflammation and liver damage due to cholangiopathies. "Since the effectiveness of currently available medical therapies to slow the progression of cholangiopathies is limited, there is an urgent need for novel and effective medical treatment strategies," Trauner and colleagues wrote. In their experiment, the researchers fed mice a diet enriched with 4% curcumin by weight for four and eight weeks. The mice were Mdr2-/-, a genetically altered strain that spontaneously develops progressive inflammatory conditions of the liver, including primary sclerosing cholangitis and primary biliary cirrhosis. These conditions can cause the liver bile ducts to become inflamed, scarred, and blocked, which leads to extensive tissue damage and fatal liver cirrhosis. A control group of Mdr2-/- mice was fed a typical diet containing no curcumin. The researchers analyzed tissue and blood samples from the mice before and after adding curcumin to their diet. They found that curcumin reduced bile duct blockage and liver cell damage at both four and eight weeks by blocking portal myofibrocyte proliferation and decreasing expression of vascular cell adhesion molecule-1, thus reducing inflammation and fibrosis. No such delay in liver fibrosis was seen in the control group. "These results show that curcumin may have multiple targets in liver, including activation of PPARgamma in cholangiocytes and inhibition of ERK1/2 signaling in portal myofibroblasts, thereby modulating several central cellular events in a mouse model of cholangiopathy," they wrote. "Targeting these pathways may be a promising therapeutic approach to cholangiopathies." They pointed out that curcumin might represent an alternative to ursodeoxycholic acid, the only current drug treatment for inflammatory liver disease, or liver transplant. The long-term effects of ursodeoxycholic acid remain unclear, they wrote, and curcumin might present a natural, well-tolerated option. The study was funded by the Austrian Science Foundation and the Medical University of Graz. The authors reported that they had no financial conflicts of interest. Primary source: Gut Source reference: Trauner M, et al "Curcumin improves sclerosing cholangitis in Mdr2-/- mice by inhibition of cholangiocyte inflammatory response and portal myofibroblast proliferation" Gut 2010; 59: 521-30.