Propolis

an ancient remedy may fight AIDS

Bees collect a gummy plant resin called propolis on their back legs and use it to line the entries to the hive, making those hives some of the most sterile environments on Earth. Researchers at the U are finding that propolis may also help fight AIDS.

By Deane Morrison

Published on May 24, 2004

As if bees don't do enough for us already, U of M researchers have recruited the busy insects in the fight against AIDS. Bees collect a plant resin that inhibits growth of the AIDS virus in laboratory cultures, and the researchers are exploring its potential as a source of a new anti-HIV drug.

Called propolis, the gummy substance has been used medicinally since ancient times. It helps control bacteria, inflammation, infectious yeast, and viruses, and you can buy it commercially in a variety of formulations.

"It's actually resin from particular trees--birch, poplar, some conifers," says bee expert Marla Spivak, an associate professor of entomology at the U. "Bees pick it up on their back legs and use it to line the entries to the hive and to seal cracks in the hive." Thanks largely to propolis, beehives are one of the most sterile environments on Earth--a good thing for a dwelling with thousands of inhabitants.

According to Phil Peterson, professor of medicine and director of the University's Division of Infectious Diseases and International Medicine, the need for a new AIDS drug could not be more urgent.

U researcher Lana Barkawi has found some of the strongest anti-HIV activity in propolis from southeast and northern Minnesota and from China.

"About 36 million people are infected with HIV (the AIDS virus), and 20 million have died of AIDS," he says. "Seventy-five percent of the deaths have occurred in sub-Saharan Africa, but the epidemic is rapidly shifting to India and Southeast Asia. Every day there are 16,000 new infections."

About a year ago, HIV passed tuberculosis as the world's number one infectious disease. TB remains the top opportunistic infection in HIV patients, however, and it will wreak havoc in places like India, where sanitation and access to high-quality health care is often poor.

In many countries, the cost of current AIDS drug therapies is prohibitive. The three-drug "cocktail" that revolutionized AIDS treatment in the developed world costs $10,000 a year in the United States, says Peterson. In India, where generic formulations of the drugs are available, it's $180 a year, but for a country whose average income is $400 a year, that's still out of reach.

At the U, the race is on to document the specific anti-HIV functions of propolis, determine which of its components are active, and find the geographical areas where the most effective propolis is made, all in hopes of discovering an effective but cheaper drug.

Peterson and his colleagues have examined the ability of propolis to stymie HIV infections. HIV destroys the immune system by infecting white blood cells called CD4 lymphocytes, the very cells that normally would destroy a virus. HIV also attacks brain cells called microglia, which help fight off infections in the nervous system.

The researchers grew the cells in culture with varying amounts of propolis and added HIV. They found that the more propolis, the less HIV grew inside the cells. Evidence suggested that propolis was preventing the virus from entering the cells. Propolis also seemed to work synergistically with the AIDS drug AZT.

The U's Center for Drug Design--headed by Robert Vince, the principal developer of the AIDS drug Ziagen--is also involved in the effort. For example, senior associate director Ramaiah Muthyala has found that propolis inhibits enzymes that help HIV get established in the genomes of host cells. It also inhibits the enzymes that help the virus replicate. Conducting the tests was center member Jay Brownell, who noted that propolis inhibits these enzymes much better than some clinically used drugs, such as amprenavir and indinavir. Muthyala's major effort centers on identifying the chemical structure of the active component in propolis--once it's isolated--and developing a means of synthesizing that active molecule in the laboratory.

These results are encouraging, but plenty remains to be done. Recognizing the variability in trees and bees, Lana Barkawi, working in entomology professor Jerry Cohen's lab, is testing propolis from around the world. She has found some of the strongest anti-HIV activity in propolis from southeast and northern Minnesota and from China. Cohen and Barkawi are also trying to identify the substance(s) in propolis responsible for its anti-HIV properties.

"If you want to get this approved by the FDA, you will have to standardize it," says Peterson. "We believe it's critically important to find the active ingredients in propolis."

The propolis project is an example of interdisciplinary research fostered by the U's Center for Plants and Human Health. Center director Gary Gardner is also an active member of the propolis team. The work is funded by a $32,000 grant-in-aid from the Graduate School.