Grapefruit Flavonoid Inhibits Hepatitis C

Stimulation with the grapefruit flavonoid naringenin inhibits hepatitis C virus (HCV) secretion in infected cells, according to a new study in the May issue of Hepatology. These findings suggest a new approach to help treat the disease. Hepatology is a journal published by John Wiley & Sons on behalf of the American Association for the Study of Liver Diseases (AASLD).

About three percent of the world’s population is infected with Hepatitis C virus, which can lead to cirrhosis and liver cancer. The current standard therapy of interferon and ribavirin is only effective in about 50 percent of cases and can cause significant side effects. As a result, there is a pressing need for alternative treatment strategies.

Recent studies have shed light on how HCV operates and suggest that the virus might be ‘hitching a ride’ along the lipoprotein lifecycle. Therefore, compounds and dietary supplements that influence lipoprotein metabolism might also affect HCV. To test this hypothesis, researchers led by Yaakov Nahmias of Harvard Medical School, examined HCV secretion and the effects of the grapefruit flavonoid naringenin on it.

They demonstrated that HCV is actively secreted by infected cells through a Golgi-dependent mechanism, while bound to a very low-density lipoprotein. "Silencing apolipoprotein B (Apo-B) mRNA in infected cells causes a 70 percent reduction in the secretion of both ApoB-100 and HCV," they report. "This ApoB-dependent HCV secretion pathway suggests a novel therapeutic approach for the treatment of HCV infection."

They then examined the effect of the grapefruit flavonoid naringenin on HCV secretion, since the compound is known to significantly reduce plasma cholesterol and triglyceride levels. They found that naringenin reduces HCV secretion in infected cells by 80 percent. They tested its toxicity to freshly isolated human hepatocytes, and found it to be safe in concentrations over 1000 µM.

"The concept of supplementing HCV patients’ diets with naringenin is appealing," the authors write, though they note that the intestinal wall does not absorb it well. Instead, therapeutic doses would need to be delivered intravenously or combined with other compounds in order to increase its bioavailability.

It is important to note that several compounds in grapefruit, including naringenin, are known to have significant drug-drug interactions. Patients on immunosuppressive medication such as Neoral (cyclosporine) or those taking protease inhibitors used to treat human immunodeficiency virus such as Norvir (ritonavir) may be at particular risk.

"Future studies would focus on long-term ability of naringenin and perhaps other citrus flavonoids to reduce viral load in animal models and long-term cultures of primary human hepatocytes," they conclude.

Source: John Wiley & Sons, Inc.