Albendazole is the most common worm expeller used for roundworm treatment, but it has many drawbacks. The quest for alternative compounds are, therefore, a target for researchers.
Now, researchers have found that nifedipine, a medicine for lowering blood pressure, and the extract of the flowers of Chrysanthemum coronarium could be therapeutic repurposed drugs for treating different developmental stages of Trichinella spiralis, commonly known as pork worm.
It was in the 2023 edition of the BMC Complementary Medicine and Therapies journal.
Nifedipine gained attention due to the discovery of its anti-parasitic properties, mainly against germs that cause diseases such as malaria, schistosoma, and Leishmania.
Trichinellosis is a type of roundworm infection. It is a serious zoonotic disease (an animal disease that can infect humans) that is caused by consuming undercooked or raw meat, usually pork, and wild game containing Trichinella infective larvae.
The signs, symptoms, severity, and duration of trichinellosis vary. Nausea, diarrhoea, vomiting, fatigue, fever, and abdominal discomfort are often the first symptoms of trichinellosis.
Headaches, fevers, chills, coughs, swelling of the face and eyes, aching joints and muscle pains, itchy skin, diarrhoea, or constipation may follow the first symptoms. If the infection is heavy, patients may experience difficulty coordinating movements and have heart and breathing problems. In severe cases, death can occur.
When a human or animal eats meat that contains infective Trichinella larvae, the acid in the stomach dissolves the hard covering of the cyst around the larvae and releases the worms. The worms pass into the small intestine and, in a day or two, become mature.
After mating, adult females lay eggs. Eggs develop into immature worms, travel through the arteries, and are transported to muscles. Within the muscles, the worms curl into a ball and encyst (become enclosed in a capsule). The life cycle repeats when meat containing these encysted worms is consumed by another human or animal.
The deworming drugs that act against infections caused by this parasitic worm are benzimidazole derivatives. However, they have numerous drawbacks, as none of these drugs is powerful enough to kill encapsulated and new-born larvae and prevent the development of drug resistance. Likewise, most of them are not advisable for use by pregnant women or children under two years of age.
Therefore, scientific research aims to discover a novel, secure, and effective deworming agent against pork worms. In addition, drug repurposing, the process of identifying a new application for drugs, has recently emerged as a tool for developing new indications for existing, failed, or abandoned drugs.
On the other hand, there is a growing need to find new therapeutic natural agents as a simple replacement for synthetic chemical agents.
Chrysanthemum coronarium is a popular dietary supplement in China that has been shown to have many medicinal properties. Commonly called Crown Daisy, Chrysanthemum coronarium has been demonstrated to also have insecticidal and herbicide effects.
For the study, the effects of different concentrations of albendazole, nifedipine, and the extract of the flowers of Chrysanthemum coronarium were assessed on adult worms and muscle larvae of pork worms.
Mice were orally infected with pork worms, and afterwards, adult worms and larvae of the worm were harvested from the intestines of infected mice. They were sacrificed under light anaesthesia, and their intestines were removed and opened with scissors. In addition, muscle larvae were also obtained from infected mice.
The studied drugs showed a remarkable lethal effect on the adult forms and muscle larvae of the pork worm in a dose- and time-dependent fashion under laboratory conditions. Albendazole showed a statistically significant effect after 96 hours. It also killed all larvae after 48 hours in concentrations starting at 100 µg/ml. remarkable lethal effects on adult forms and muscle larvae.
As regards nifedipine, a significant larvicidal effect was obtained at a concentration of 0.78 µg/ml after four hours. In addition, it killed all larvae after 72 hours in concentrations starting at 3.125 µg/ml. Chrysanthemum coronarium killed 100% of larvae at a high concentration (400 µg/ml) after 96 hours.
Albendazole killed all worms after 24 hours in concentrations starting at 200 µg/ml. Nifedipine killed all worms after 4 hours in concentration starting at 6.25 µg/ml. Chrysanthemum coronarium caused the death of all adult worms at high concentrations (200 µg/ml and 400 µg/ml) after 72 hours.
The largest anthelmintic drug-repurposing success story by far has been the application of malaria medicines against a wide variety of flatworm infections, as well as other broader applications. Investigations of the use of antimalarials against Schistosoma spp. and the liver flukes are based on the rationale that these flukes have the same blood-feeding characteristics as malaria parasites.
However, antimalarials have also shown activity against non-blood-feeding intestinal flukes, but experts caution that the use of malaria medicines in de-worming programmes should be approached with caution, as this could accelerate resistance to these drugs.
