Abstract:
Conventional therapy of visceral leishmaniasis (VL) remains challenging with the pitfall of toxicity, drug resistance,
and expensive. Hence, urgent need for an alternative approach is essential. In this study, we evaluated the
potential of combination therapy with eugenol oleate and miltefosine in Leishmania donovani infected macrophages
and in the BALB/c mouse model. The interactions between eugenol oleate and miltefosine were found to
be additive against promastigotes and amastigotes with xΣFIC 1.13 and 0.68, respectively. Significantly (p <
0.001) decreased arginase activity, increased nitrite generation, improved pro-inflammatory cytokines, and
phosphorylated p38MAPK were observed after combination therapy with eugenol oleate and miltefosine. >80%
parasite clearance in splenic and hepatic tissue with concomitant nitrite generation, and anti-VL cytokines
productions were observed after orally administered miltefosine (5 mg/kg body weight) and eugenol oleate (15
mg/kg body weight) in L. donovani-infected BALB/c mice. Altogether, this study suggested the possibility of an
oral combination of miltefosine with eugenol oleate against visceral leishmaniasis.
