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

表没食子儿茶素 3-O-没食子酸酯对热带利什曼原虫的抗利什曼原虫和免疫调节作用:细胞凋亡和基因表达谱

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作者: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

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.

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.

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).

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