Anti-Leishmanial and Immunomodulatory Effects of Epigallocat-echin 3-O-Gallate on Leishmania tropica: Apoptosis and Gene Expression Profiling

Morteza  SADUQI; Iraj  SHARIFI; Zahra  BABAEI; Alireza  KEYHANI; Mahshid   MOSTAFAVI; Maryam  HAKIMI PARIZI; Mahdiyeh  GHASEMIAN; Mehdi  BAMOROVAT; Fatemeh  SHARIFI; Mohammad Reza  AFLATOONIAN; Fariba  SHARIFIFAR; Pooya  GHASEMI NEJAD; Ahmad  KHOSRAVI; Ehsan  SALARKIA; Rajender S.  VARMA

doi:10.18502/ijpa.v14i4.2094

Morteza SADUQI
Iraj SHARIFI
Zahra BABAEI
Alireza KEYHANI
Mahshid MOSTAFAVI
Maryam HAKIMI PARIZI
Mahdiyeh GHASEMIAN
Mehdi BAMOROVAT
Fatemeh SHARIFI
Mohammad Reza AFLATOONIAN
Fariba SHARIFIFAR
Pooya GHASEMI NEJAD
Ahmad KHOSRAVI
Ehsan SALARKIA
Rajender S. VARMA

DOI: https://doi.org/10.18502/ijpa.v14i4.2094

Keywords: Epigallocatechin 3-O-gallate; Leishmania tropica; Immunomodulatory role; Apoptosis; Gene expression

Abstract

Background: Pentavalent antimonials such as meglumine antimoniate (MA, Glucantime), are the first-line treatment against leishmaniasis, but at present, they have basically lost their efficacy. This study was aimed to explore epigallocatechin 3-O-gallate (EGCG), alone or in combination with MA against Leishmania tropica stages.

Methods: All experiments were carried out in triplicate using colorimetric assay, macrophage model, flow cytometry and quantitative real-time PCR. This experimental study was carried out in 2017 in Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.

Results: Promastigotes and amastigotes were more susceptible to EGCG than MA alone, but the effect was more profound when used in combination. EGCG exhibited high antioxidant level with a remarkable potential to induce apoptosis. Furthermore, the results showed that the level of gene expression pertaining to Th-1 was significantly up-regulated (P<0.001).

Conclusion: EGCG demonstrated a potent anti-leishmanial effect alone and more enhanced lethal activity in combination. The principal mode of action entails the stimulation of a synergistic response and up-regulation of the immunomodulatory role towards Th-1 response against L. tropica.