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Background: Although leishmaniasis is regarded as a public health problem, no effective vaccine or decisive treatment has been introduced for this disease. Therefore, representing novel therapeutic proteins is essential. Protein-protein Interaction network analysis is a suitable tool to discover novel drug targets for leishmania major. To this aim, gene and protein expression data is used for instructing protein network and the key proteins are highlighted.Materials and Methods: In this computational and bioinformatics study, the protein/gene expression data related to leishmania major were studied, and 252 candidate proteins were extracted. Then, the protein networks of these proteins were explored and visualized by using String database and Cytoscape software. Finally, clustering and gene ontology were performed by MCODE and PANTHER databases, respectively.Results:  Based on gene ontology analysis, most of the leishmania major proteins were located in cell compartments and membrane. Catalytic activity and binding were regarded as the relevant molecular functions and metabolic and cellular processes were the significant biological process. In this network analysis, UB-EP52, EF-2, chaperonin, Hsp70.4, Hsp60, tubulin alpha and beta chain, and ENOL and LACK were introduced as hub-bottleneck proteins. Based on clustering analysis, Lmjf.32.3270, ENOL and Lmjf.13.0290 were determined as seed proteins in each cluster.Conclusion: The results indicated that hub proteins play a significant role in pathogenesis and life cycle of leishmania major. Further studies of hubs will provide a better understanding of leishmaniasis mechanisms. Finally, these key hub proteins could be a suitable and helpful potential for drug targets and treating leishmaniasis by considering their validation. [GMJ.2018;7:e1129]

Background & Objective: Leishmaniasis is among the seven more significant tropical diseases, and it is a major global health issue with a wide range of clinical symptoms and potentially lethal consequences. Resveratrol and its derivatives have been shown to have anti-Leishmanial properties. This study aimed to use a metaanalysis of relevant papers to determine the leishmanicidal impact of resveratrol and its derivatives. Materials & Methods:A comprehensive search method was used to query the electronic databases of PubMed, ScienceDirect, Embase, ISI Web of Science, and Scopus up until June 2021. The articles that met the inclusion criteria were chosen. Random-effects models were used to calculate mean differences in IC50 (concentration corresponding to a 50% reduction in Leishmania) for each outcome. The Newcastle-Ottawa Scale was used to assess the quality of the evidence. To assess heterogeneity and the stability of the pooled data, sensitivity and subgroup analyses were performed. The Egger's and Begg's tests were used to assess publication bias. Results:In the meta-analysis, nine studies were considered. Resveratrol (RSV) and its derivatives significantly reduced survivability in Leishmania promastigote [24.02 µg/ml; (95% CI 17.1, 30.8); P<0.05; I 2 = 99.8%; P Heterogeneity = 0.00] and amastigote [18.3 µg/ml; (95% CI 13.5, 23.2); P<0.05; I 2 = 99.6%; P Heterogeneity= 0.00]. The metaanalysis revealed a considerable publication bias. Sensitivity analyses revealed that the effect magnitude was similar, but the heterogeneity was reduced. According to subgroup analysis, the pooled effect sizes of leishmanicidal resveratrol and its derivatives were altered by the kind of stilbenes and Leishmania species. Conclusion:According to the findings of this meta-analysis, RSV and its derivatives could be a possible therapeutic option for leishmaniasis. However, more research is needed to confirm and employ this chemical against Leishmania.

Background Leishmaniasis is one of the most important health problems worldwide. The evidence has suggested that resveratrol and its derivatives have anti-leishmanial effects; however, the results are inconsistent and inconclusive. The aim of this study was to assess the effect of resveratrol and its derivatives on the Leishmania viability through a systematic review and meta-analysis of available relevant studies. Methods The electronic databases PubMed, ScienceDirect, Embase, Web of Science and Scopus were queried between October 2000 and April 2020 using a comprehensive search strategy. The eligible articles selected and data extraction conducted by two reviewers. Mean differences of IC50 (concentration leading to reduction of 50% of Leishmania) for each outcome was calculated using random-effects models. Sensitivity analyses and prespecified subgroup were conducted to evaluate potential heterogeneity and the stability of the pooled results. Publication bias was evaluated using the Egger’s and Begg’s tests. We also followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for this review. Results Ten studies were included in the meta-analysis. We observed that RSV and its derivatives had significant reducing effects on Leishmania viability in promastigote [24.02 µg/ml; (95% CI 17.1, 30.8); P < 0.05; I2 = 99.8%; P heterogeneity = 0.00] and amastigote [18.3 µg/ml; (95% CI 13.5, 23.2); P < 0.05; I2 = 99.6%; P heterogeneity = 0.00] stages of Leishmania. A significant publication bias was observed in the meta-analysis. Sensitivity analyses showed a similar effect size while reducing the heterogeneity. Subgroup analysis indicated that the pooled effects of leishmanicidal of resveratrol and its derivatives were affected by type of stilbenes and Leishmania species. Conclusions Our findings clearly suggest that the strategies for the treatment of leishmaniasis should be focused on natural products such as RSV and its derivatives. Further study is needed to identify the mechanisms mediating this protective effects of RSV and its derivatives in leishmaniasis.