The compound epigallocatechin-3-gallate (EGCG), an antioxidant derived from green tea, inhibits neurotoxicity in a mouse model of HIV-associated dementia, Dr. Brian Giunta reported this week at a session of Experimental Biology 2007 in Washington, DC.
However, the concentration of EGCG in tea is not large enough to exert any therapeutic benefit in the presence of HIV infection, Dr. Giunta told Reuters Health, "and oral administration is unlikely to cross the blood-brain barrier."
The neuronal damage associated with HIV proteins is increased when interferon-gamma is present. Interferon-gamma activates the JAK/STAT1 pathway, thereby increasing inflammation and apoptotic signaling to neurons.
Because "EGCG blocks the signaling between JAK/STAT1 and interferon-gamma," Dr. Giunta said, he and his associates at the University of South Florida in Tampa theorized that EGCG may be neuroprotective in the presence of HIV.
To develop a murine model of HIV-dementia, Dr. Giunta and colleagues injected the HIV proteins Tat and gp120 into the cerebral ventricles of mice, along with interferon-gamma. After 24 hours, histological examination of the animals' brains showed damage similar to that found in brains of patients with HIV-related dementia.
The researchers then administered EGCG by intraperitoneal injection to other mice, immediately after the HIV proteins and interferon were injected into the ventricles. The 24-hour examination of brain tissue demonstrated a marked reduction in neuronal damage.
Dr. Giunta believes that EGCG will turn out to be a safer and more effective agent than "artificial compounds found by high-throughput screening. Many times the compounds identified this way are toxic or are not bioavailable."
EGCG "is a natural product shown to be safe in humans at doses up to 80 mg/day," he continued. Furthermore, "testing in rats, mice, and dogs have shown that the drug is not xenotoxic, teratogenic or genotoxic."
Animal studies suggest that EGCG may also be neuroprotective in other neurologic conditions, Dr. Giunta added, including Alzheimer's disease, autoimmune encephalitis, and stroke, and perhaps Parkinson's disease.
Copyright© 2007 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
