A Systematic Review of Curcumin and its Derivatives as Valuable Sources of Antileishmanial Agents

Background: In recent years, antimonial agents and other synthetic antileishmanial drugs, such as amphotericin B, paromomycin, and many other drugs, have restrictions in use due to the toxicity risk, high cost, and emerging resistance to these drugs. The present study aimed to review the antileishmanial effects of curcumin, its derivatives, and other relevant pharmaceutical formulations on leishmaniasis. Methods: The present study was carried out according to the 06-preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline and registered in the CAMARADES-NC3Rs Preclinical Systematic Review and Meta-Analysis Facility (SyRF) database. Some English-language databases including PubMed, Google Scholar, Web of Science, EBSCO, Science Direct, and Scopus were searched for publications worldwide related to antileishmanial effects of curcumin, its derivatives, and other relevant pharmaceutical formulations, without date limitation, to identify all the published articles (in vitro, in vivo, and clinical studies). Keywords included �curcumin�, �Curcuma longa�, �antileishmanial�, �Leishmania�, �leishmaniasis�, �cutaneous leishmaniasis�, �visceral leishmaniasis�, �in vitro�, and �in vivo�. Results: Out of 5492 papers, 29 papers including 20 in vitro (69.0), 1 in vivo (3.4), and 8 in vitro/in vivo (27.6) studies conducted up to 2020, met the inclusion criteria for discussion in this systematic review. The most common species of the Leishmania parasite used in these studies were L. donovani (n = 13, 44.8), L. major (n = 10, 34.5), and L. amazonensis (n = 6, 20.7), respectively. The most used derivatives in these studies were curcumin (n = 15, 33.3) and curcuminoids (n = 5, 16.7), respectively. Conclusion: In the present review, according to the studies in the literature, various forms of drugs based on curcumin and their derivatives exhibited significant in vitro and in vivo antileishmanial activity against different Leishmania spp. The results revealed that curcumin and its derivatives could be considered as an alternative and complementary source of valuable antileishmanial components against leishmaniasis, which had no significant toxicity. However, further studies are required to elucidate this concluding remark, especially in clinical settings. © 2021, Witold Stefa�ski Institute of Parasitology, Polish Academy of Sciences

Fe3O4@piroctone olamine magnetic nanoparticles: Synthesize and therapeutic potential in cutaneous leishmaniasis

Background: In recent years, magnetic nanoparticles (NMP) as novel materials have been widely used for biomedical, diagnostic and therapeutic purposes like microbial infection therapy. The purpose of this study is to synthesize PO coated iron oxide magnetic nanoparticles (Fe3O4@PO NPs) and their anti-leishmanial effects in vitro and in vivo against cutaneous leishmaniasis. Methods: Fe3O4 magnetic nanoparticles were synthesized by the coprecipitation of Fe2 + and Fe3 + ions and used as a nanocarrier for the production of Fe3O4@PO NPs. The in vitro antileishmanial effects of PO-coated Fe3O4 NPs and Fe3O4 NPs (10�200 µg/mL) was determined against the intracellular amastigotes of Leishmania major (MRHO/IR/75/ER) and, then, examined on cutaneous leishmaniasis induced in male BALB/c mice by L. major. The rate of infectivity, production of nitric oxide (NO), and cytotoxic activates of Fe3O4 NPs and Fe3O4@PO NPs on J774-A1 macrophage cells were determined. Results: The size scattering of the Fe3O4 NPs and Fe3O4@PO NPs were in the range among 1�40 and 5�55 nm, respectively. The obtained IC50 values were 62.3 ± 2.15 μg/mL, 31.3 ± 2.26 μg/mL, and 52.6 ± 2.15 μg/mL for the Fe3O4 NPs and Fe3O4@PO NPs, and MA, respectively. The results revealed that the mean number of parasites and the mean diameter of the lesions was considerably (p < 0.05) decreased in the infected mice treated with Fe3O4 NPs and Fe3O4@PO NPs. The Fe3O4 NPs and Fe3O4@PO NPs significantly (p < 0.05) prompted the production of NO as a dose-dependent manner. The promastigotes pre-incubated in Fe3O4 NPs and Fe3O4@PO NPs at the concentration of 5 µg/mL had the ability to infect only 41.7 and 28.3 of the macrophages cells. The selectivity index of greater than 10 for Fe3O4 NPs and Fe3O4@PO NPs showed its safety to the J774-A1 macrophage cells and specificity to the parasite. Conclusion: The results of this survey indicated the high potency of Fe3O4@PO NPs to inhibit the growth of amastigote forms of L. major as well as recovery and improvement CL induced by L. major in BALB/c mice without significant cytotoxicity. The results also indicated that, although the possible anti-leishmanial mechanisms of Fe3O4@PO NPs have not been clearly understood, however, the triggering of NO may be considered as one of the possible anti-leishmanial mechanisms of these nanoparticles. However, additional studies, in particular in clinical contexts, are mandatory. © 2021 The Author