A study carried out by researchers at the Bengaluru-based Indian Institute of Science (IISc) has shown that garlic, well known for its medicinal properties, in the form of oil can complement and improve the efficacy of the widely used artemisinin anti-malarial drug. The combination therapy clears the parasite from mice infected with Plasmodium berghei (a mouse model which mimics Plasmodium falciparum in humans) and increases the duration of survival. The results were published recently in the journal Biochemistry and Biophysics Reports.

Plasmodium berghei parasite was used for infecting the mice as the work involved in vivo studies; Plasmodium falciparum can be used only for in vitro studies.

While mice in the control group (that did not get garlic oil) died within 4-6 days post infection, garlic oil (50 microlitre) increased the survival period to eight to nine days. The survival time was the same even when 100 microlitre and 150 microlitre of garlic oil were used, but the percentage of mice that survived up to eight days increased from 20 per cent (when 50 microlitre was used) to 60 per cent and 70 per cent when 100 microlitre and 150 microlitre of garlic oil were used.

When arteether (a semi-synthetic derivative of Artemisinin anti-malaria drug) was used, mice survived up to 21 days after infection . The protection was complete when highest dose of 1.5 mg of arteether was used. “But artemisinin is toxic at high doses and resistance sets in when used as a monotherapy,” said Dr. P.G. Vathsala, the first author of the paper from the Department of Biochemistry at IISc.

According to the WHO recommendation, artemisinin should be used in combination with other therapies as the emergence and spread of artemisinin resistance is threatening to wipe out the huge gains made during the last two decades. Artemisinin-resistant Plasmodium falciparum parasites have been found in Myanmar, just 25 km from the Indian border (The Lancet Infectious Diseases, April 15, 2015).

So the high dose of arteether was avoided; a single sub-optimal dose of 750 microgram was used instead.  At this dose, the parasites were quickly cleared from the blood (erythrocytic stage); but the parasites reappeared after 21 days and killed the mice. “We think the parasites were still present in the liver and reappeared in the blood after three weeks,” she said.

Combination therapy

Garlic oil and arteether were then used in combination. When three doses of garlic oil (50 microlitre per dose) was used along with a single dose of arteether (750 microgram) all the mice survived up to 19 days; they died between day 19 and 22.

The survival rate was 100 per cent and the duration of protection lasted much longer when higher dosages (100 microlitre and 150 microlitre) of garlic oil were used along with 750 microgram of arteether. “The combination therapy not only cured malaria but the infected mice also did not suffer any relapse. The mice have survived for three months after the combination therapy,” she said based on studies carried out after the manuscript was sent for publication in the journal.

The precise mechanism of action of arteether and garlic oil is, however, not known. Earlier studies show that arteether tends to clear the blood of parasites and the active compounds in garlic oil might have prevented infection of new blood cells.  Garlic oil might have also reduced the parasite load in the liver and spleen, notes the paper.

“We are now working on understanding the mechanism of action of garlic and studying the effects of garlic extract.  Future work will look into parasite load in liver and spleen,” Dr. Vathsala said.

Published in The Hindu on February 20, 2016