Naringenin Compound in Grapefruit Inhibits HCV Replication in Laboratory Study

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Naringenin Compound in Grapefruit Inhibits HCV Replication in

Laboratory Study

Researchers at Massachusetts General Hospital in Boston recently

reported that a compound known as maringenin, found in grapefruit and

other citrus fruits, inhibited hepatitis C virus (HCV) replication in

laboratory and animal studies by interfering with secretion of new

virus particles from infected cells.

Below is the text of a MGH press release announcing the new findings:

MGH study reveals mechanism key to maintaining chronic infection,

potential therapy target

A compound that naturally occurs in grapefruit and other citrus

fruits may be able to block the secretion of hepatitis C virus (HCV)

from infected cells, a process required to maintain chronic

infection. A team of researchers from the Massachusetts General

Hospital Center for Engineering in Medicine (MGH-CEM) report that HCV

is bound to very low-density lipoprotein (vLDL, a so-called " bad "

cholesterol) when it is secreted from liver cells and that the viral

secretion required to pass infection to other cells may be blocked by

the common flavonoid naringenin.

If the results of this study extend to human patients, a combination

of naringenin and antiviral medication might allow patient to clear

the virus from their livers. The report will appear in an upcoming

issue of the journal Hepatology and has been released online.

" By finding that HCV is secreted from infected cells by latching onto

vLDL, we have identified a key pathway in the viral lifecycle, " says

Yaakov Nahmias, PhD, of the MGH-CEM, the paper's lead author. " These

results suggest that lipid-lowering drugs, as well as supplements,

such as naringenin, may be combined with traditional antiviral

therapies to reduce or even eliminate HCV from infected patients "

HCV is the leading cause of chronic viral liver disease in the United

States and infects about 3 percent of the world population. Current

antiviral medications are effective in only half of infected

patients, 70 percent of whom develop chronic infection that can lead

to cirrhosis or liver cancer. Since the virus does not integrate its

genetic material into the DNA of infected cells the way HIV does,

totally clearing the virus could be possible if new cells were not

being infected by secreted virus.

" Identifying the route by which HCV is released from cells introduces

a new therapeutic target, " says Yarmush, MD, PhD, director of

the MGH-CEM and the paper's senior author. " That pathway's dependence

on cholesterol metabolism could allow us to interfere with viral

propagation to other cells and tissues, using tools already developed

for atherosclerosis treatment. " Yarmush is the Helen Andrus Benedict

Professor of Surgery and Bioengineering at Harvard Medical School

(HMS).

Grapefruit's bitter taste is caused the presence of the flavonoid

naringin, which is metabolized into naringenin, an antioxidant

previously reported to help lower cholesterol levels. Considerable

research has suggested that HCV infects liver cells by, in

essence, " hitching a ride " onto the natural lipoprotein-cholesterol

metabolic pathway. Since earlier evidence has shown that naringenin

can reduce secretion of vLDL from liver cells, the researchers

examined whether the compound might also lower HCV secretion from

infected cells. Their experiments confirmed that naringenin does

reduce the secretion of HCV from infected cell lines and showed that

the compound inhibits the mechanism for secreting a specific

lipoprotein that binds HCV.

" This work presents the possibility that non-toxic levels of a

dietary supplement, such as naringenin, could effectively block HCV

secretion, " says Chung, MD, MGH director of Hepatology and

one of the study authors, " This approach might eventually be used to

treat patients who do not respond to or cannot take traditional

interferon-based treatment or be used in combination with other

agents to boost success rates. "

2/15/08