**4. Licochalcone A**

infectious diseases. A comprehensive model giving the overall mechanistic insight into the mode of action of GRA as antileishmanial agent will help in deducing its function in other intramacrophage pathogens which assume similar immunoevasive mechanisms to escape host

Another constituent of licorice, which serves as an antileishmanial compound, is glycyrrhizic acid (GA) [43]. The studies using this compound showed an increase in NO production with restoration of Th1 cytokine balance and inhibition of immunosuppressive prostaglandin E2(PGE2) production. This is in line with recent evidences, which suggests that the parasite is able to induce PGE2 production via promoting inducible COX2 expression. This in turn resulted in activation of EP receptors (PGE2 receptors) on the host cell surface thereby causing Cyclic adenosine monophosphate(cAMP) induction and cytokine production [44] (**Figure 8**).

**Figure 8.** Glycyrrhizic acid mediated PGE2 inhibition and NO and proinflammatory cytokine production helps para-

This is also anticipated as glycyrrhizic acid is readily hydrolyzed to glycyrrhetinic acid in human body [45] which is already discussed in details to have antileishmanial activities. Recent studies further shows that this compound when used in conjunction with antimonials can help in overcoming the resistance seen in the antimony resistant parasites. Extensive use of the antimonials and low follow-up of cases had led to emergence of antimonial resistant strains of the parasite [46]. The main criteria for this resistance is attributed to the overexpression and

defenses (**Figure 7**).

site suppression.

**3. Glycyrrhizic acid**

156 Biological Activities and Action Mechanisms of Licorice Ingredients

The oxygenated chalcone, licochalcone A, has also been extensively studied to understand the mechanism of this compound as an antileishmanial agent [48–50]. Previous studies have shown its effect as antioxidant, antimicrobial and anti-tumor promoting properties [51, 52]. The use of this compound in infection particularly affected the amastigote forms of the parasite and to a lesser extent the promastigote form having practically no effect on the host monocytes even at higher concentrations. The main target of licochalcone A was the mitochondrion of the parasite, whereas the host mitochondrion remained unaffected [48]. 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 O2 consumption and CO2 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**).

**Figure 10.** The effect of licochalcone A on the mitochondrion of the *Leishmania* parasite.
