Studies on serine protease inhibitor from coccinia grandis L voigt in immunomodulation and host cell signaling by leishmania donovani a therapeutic approach in experimental visceral leishmaniasis

Abstract

Leishmaniasis is ranked as a second most important vector-born parasitic disease after malaria in the tropical regions. The disease has divergent clinical manifestations including the cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL) and visceral leishmaniasis (VL), which occurs by the eukaryotic protozoan parasite of genus Leishmania within macrophages. CL can spontaneously heal with disfiguring scars and MCL requires treatment to cure whereas VL is associated with mortality in human due to the improper diagnosis and treatment. A dermal sequela of the VL is known as the Post Kala-azar Dermal Leishmaniasis (PKDL) appearing as papular, macular or nodular rash generally on upper arms, face and other regions of the body [Pace D., 2014]. These clinical syndromes depend on the type of parasite species and immune responses of the host. Leishmaniasis is transmitted to mammals by the insect vector like female Phlebotomine or Leutzomiya sand fly throughout the tropical and sub-tropical regions [Burza S et al., 2018]. From hundred endemic countries about 0.7 1 million new cases of leishmaniasis are reported each year. In east Africa, new VL cases are continuously developed and sustain the disease as well as the new case reports are recently found in Asian countries. newlineThe therapeutic regimen for leishmaniasis is solely dependent on the chemotherapy as there is no available effective vaccine. Presently, conventional drugs are used as monotherapy or combination therapy for the treatment of leishmaniasis. Pentavalent antimonials are used as primary chemotherapeutic drug from 1945 for treatment of leishmaniasis. However, the emergence of drug resistance issues and toxicity of this drug such as pancreatitis, pancytopenia, renal side effects, hepatotoxicity, gastrointestinal problems and cardiotoxicity necessitated to develop the clinically effective second line of drugs [Hussain H et al., 2014; Ponte-Sucre A et al., 2017].