Antileishmanial activity of licochalcone A in mice infected with Leishmania major and in hamsters infected with Leishmania donovani

Abstract

This study was designed to examine the antileishmanial activity of the oxygenated chalcone licochalcone A in mice and hamsters infected with Leishinunia parasites. Intraperitoneal administration of licochalcone A at doses of 2.5 and 5 mg/kg of body weight per day completely prevented lesion development in BALB/c mice infected with Leishmania major. Treatment of hamsters infected with L. donovani with intraperitoneal administration of licochalcone A at a dose of 20 mg/kg of body weight per day for 6 consecutive days resulted in a >96% reduction of parasite load in the liver and the spleen compared with values for untreated control animals. The [3H]thymidine uptake by the parasites isolated from the treated hamsters was only about 1% of that observed in parasites isolated from the controls. Oral administration of licochalcone A at concentrations of 5 to 150 mg/kg of body weight per day for 6 consecutive days resulted in >65 and 85% reductions ofL. donovani parasite loads in the liver and the spleen, respectively, compared with those of untreated control hamsters. These data clearly demonstrate that licochalcone A is a promising lead for the development of a new drug against leishmaniases.The World Health Organization has identified leishmaniases as a major and increasing public health problem (23,26). The visceral form of the disease, known as kala-azar, is widely distributed in many parts of the world, particularly Africa, Asia, Latin America, the Middle East, and the Mediterranean Basin (13,23,26

The antileishmanial agent licochalcone A interferes with the function of parasite mitochondria

“…Licochalcone A. Licochalcone A was synthesized in our laboratory as previously described (6,7), and it was dissolved in 2% dimethyl sulfoxide in medium 199 to prepare a working solution of 1 mg/ml.…”

“…Our previous studies have shown that licochalcone A, an oxygenated chalcone, inhibits the in vitro growth of both Leishmania major and L. donovani promastigotes, exhibits a remarkably strong ability to kill the intracellular parasites of L. major amastigotes (5), prevents lesion development in mice infected with L. major, and reduces the parasite load in the spleens and livers of hamsters infected with L. donovani (6). Licochalcone A also exhibits potent antimalarial activity both in vitro and in vivo (7).…”

Bioactive Component of Licorice as an Antileishmanial Agent

“…The reason for the same is still unknown but further studies suggested that the parasite respiratory rate was affected resulting in an overall decrease in parasite O 2 consumption and CO 2 production with a decrease in the activity of the mitochondrial dehydrogenases [50]. In vivo studies also showed high parasite elimination in in vivo studies upon intraperitoneal administration of licochalcone A as opposed to intralesional or oral administration [49]. All these findings suggests potential role of licochalcone A as an antileishmanial agent although studies understanding the mechanism of this compound is still underway (Figure 10).…”

“…The oxygenated chalcone, licochalcone A, has also been extensively studied to understand the mechanism of this compound as an antileishmanial agent [48][49][50]. Previous studies have shown its effect as antioxidant, antimicrobial and anti-tumor promoting properties [51,52].…”

Leishmaniasis: Drug resistance and natural products (Review)

“…IC 50 value of licochalcone A against L. donovani intracellular amastigote was 0.9 μg/ml (2.7 μM) and 7.2 μg/ml (21 μM) against L. major promastigotes (64). In vivo studies with hamsters have shown that the parasite load in the spleen and liver was reduced up to 96% (20 mg/ kg body weight x 6 days) (65). Other oxygenated chalcones exhibited comparable potency (64).…”