Generic placeholder image

Infectious Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5265
ISSN (Online): 2212-3989

Research Article

The Effect of Curcumin on the Expression of INFγ, TNF-α, and iNOS Genes in PBMCs Infected with Leishmania major [MRHO/IR/75/ER]

Author(s): Soheila Alinejad, Shahram Khademvatan*, Shahla Amani*, Negar Asadi, Khosrow Hazrati Tappeh, Elham Yousefi and Touraj Miandoabi

Volume 22, Issue 6, 2022

Published on: 15 June, 2022

Article ID: e040422203031 Pages: 7

DOI: 10.2174/1871526522666220404083220

Price: $65

Abstract

Background: Leishmaniasis, caused by the Leishmania parasite, is one of the most important tropical neglected diseases. The urgent search for effective, inexpensive, and preferably herbal anti-leishmanial agents, is needed.

Objective: Curcumin is a natural polyphenolic compound derived from turmeric that is well known for its antioxidant, anti-inflammatory, anti-tumor, and anti-cancer activity.

Methods: The present work evaluates the anti-leishmanial [Leishmania major] activity of curcumin. The infected PBMCs were treated with curcumin. The ROS level at 6, 12, 24 h and gene expression levels at 24, 48, and 72 h of PBMCs after treatment with curcumin were determined.

Results: Based on the results, the curcumin concentrations of 268 μM [24 h] and 181.2 μM [72 h] were defined as IC50 against L. major promastigotes. Treatment of L. major infected-peripheral blood mononuclear cells [PBMCs] with IC50 concentrations of curcumin, depending on exposure time, significantly induced the reactive oxygen species [ROS] generation and increased the expression levels of interferongamma [IFN-γ], tumor necrosis factor-alpha [TNF-α], and nitric oxide synthase [iNOS] genes.

Conclusion: These findings suggest the potential of curcumin against Leishmaniasis.

Keywords: Curcumin, gene expression, Leishmania major, PBMCs, tumor necrosis factor, interferon gamma.

Graphical Abstract

[1]
Saki J, Meamar A, Oormazdi H, et al. Mini-exon genotyping of leishmania species in khuzestan province, southwest iran. Iran J Parasitol 2010; 5(1): 25-34.
[PMID: 22347232]
[2]
Foroutan M, Khademvatan S, Majidiani H, et al. Prevalence of Leishmania species in rodents: A systematic review and meta-analysis in Iran. Acta Trop 2017; 172: 164-72.
[http://dx.doi.org/10.1016/j.actatropica.2017.04.022] [PMID: 28454881]
[3]
Gambino D. Potentiality of vanadium compounds as anti-parasitic agents. Coord Chem Rev 2011; 255(19-20): 2193-203.
[http://dx.doi.org/10.1016/j.ccr.2010.12.028]
[4]
Cortes S, Bruno de Sousa C, Morais T, Lago J, Campino L. Potential of the natural products against leishmaniasis in old world - a review of in-vitro studies. Pathog Glob Health 2020; 114(4): 170-82.
[http://dx.doi.org/10.1080/20477724.2020.1754655] [PMID: 32339079]
[5]
Mcgwire BS, Satoskar A. Sir William Osler medicine master class leishmaniasis: Clinical syndromes and treatment. 2013.
[http://dx.doi.org/10.1093/qjmed/hct116]
[6]
Oryan A. Plant-derived compounds in treatment of leishmania-sis. Majallah-i Tahqiqat-i Dampizishki-i Iran 2015; 16(1): 1-19.
[PMID: 27175144]
[7]
Kaye P, Scott P. Leishmaniasis: Complexity at the host-pathogen interface. Nat Rev Microbiol 2011; 9(8): 604-15.
[http://dx.doi.org/10.1038/nrmicro2608] [PMID: 21747391]
[8]
Antonelli LR, Dutra WO, Almeida RP, Bacellar O, Carvalho EM, Gollob KJ. Activated inflammatory T cells correlate with lesion size in human cutaneous leishmaniasis. Immunol Lett 2005; 101(2): 226-30.
[http://dx.doi.org/10.1016/j.imlet.2005.06.004] [PMID: 16083969]
[9]
Sharma U, Singh S. Immunobiology of leishmaniasis 2009.http://hdl.handle.net/123456789/4364
[10]
Wanasen N, Soong L. L-arginine metabolism and its impact on host immunity against Leishmania infection. Immunol Res 2008; 41(1): 15-25.
[http://dx.doi.org/10.1007/s12026-007-8012-y] [PMID: 18040886]
[11]
Qadoumi M, Becker I, Donhauser N, Röllinghoff M, Bogdan C. Expression of inducible nitric oxide synthase in skin lesions of patients with american cutaneous leishmaniasis. Infect Immun 2002; 70(8): 4638-42.
[http://dx.doi.org/10.1128/IAI.70.8.4638-4642.2002] [PMID: 12117977]
[12]
Sinha S, Sundaram S, Singh AP, Tripathi A. A gp63 based vac-cine candidate against visceral leishmaniasis. Bioinformation 2011; 5(8): 320-5.
[http://dx.doi.org/10.6026/97320630005320] [PMID: 21383918]
[13]
Yousefi E, Eskandari A, Javad Gharavi M, Khademvatan S. In vitro activity and cytotoxicity of Crocus sativus extract against Lei-hmania major (MRHO/IR/75/ER). Infect Disord Drug Targets 2014; 14(1): 56-60.
[14]
Khademvatan S, Gharavi MJ, Rahim F, Saki J. Miltefosine-induced apoptotic cell death on Leishmania major and L. tropica strains. Korean J Parasitol 2011; 49(1): 17-23.
[http://dx.doi.org/10.3347/kjp.2011.49.1.17] [PMID: 21461264]
[15]
Khademvatan S, Eskandari A, Saki J, Foroutan-Rad M. Cytotox-ic activity of Holothuria leucospilota extract against Leishmania infantum in vitro Adv Pharmacol Sci 2016; 2016.
[16]
Khademvatan S, Adibpour N, Eskandari A, Rezaee S, Hash-emitabar M, Rahim F. In silico and in vitro comparative activity of novel experimental derivatives against Leishmania major and Leishmania infantum promastigotes. Exp Parasitol 2013; 135(2): 208-16.
[http://dx.doi.org/10.1016/j.exppara.2013.07.004] [PMID: 23872452]
[17]
Mohebali M, Rezayat M, Gilani K, et al. Nanosilver in the treatment of localized cutaneous leishmaniasis caused by Leishmania major (MRHO/IR/75/ER): An in vitro and in vivo study. Daru 2015; 17(4): 285-9.
[18]
Foroutan-Rad M, Khademvatan S, Saki J, Hashemitabar M. Holothuria leucospilota extract induces apoptosis in Leishmania major promastigotes. Iran J Parasitol 2016; 11(3): 339-49.
[PMID: 28127339]
[19]
David B, Wolfender J-L, Dias DA. The pharmaceutical industry and natural products: Historical status and new trends. Phytochem Rev 2015; 14(2): 299-315.
[http://dx.doi.org/10.1007/s11101-014-9367-z]
[20]
Steinfeld B, Scott J, Vilander G, et al. The role of lean process improvement in implementation of evidence-based practices in behavioral health care. J Behav Health Serv Res 2015; 42(4): 504-18.
[http://dx.doi.org/10.1007/s11414-013-9386-3] [PMID: 24464179]
[21]
Pari L, Tewas D, Eckel J. Role of curcumin in health and dis-ease. Arch Physiol Biochem 2008; 114(2): 127-49.
[http://dx.doi.org/10.1080/13813450802033958] [PMID: 18484280]
[22]
Liu Y-M, Zhang Q-Z, Xu D-H, et al. Antiparasitic efficacy of curcumin from Curcuma longa against Ichthyophthirius multi-filiis in grass carp. Vet Parasitol 2017; 236: 128-36.
[http://dx.doi.org/10.1016/j.vetpar.2017.02.011] [PMID: 28288756]
[23]
Rauf A, Imran M, Orhan IE, Bawazeer S. Health perspectives of a bioactive compound curcumin: A review. Trends Food Sci Technol 2018; 74: 33-45.
[http://dx.doi.org/10.1016/j.tifs.2018.01.016]
[24]
Reddy RC, Vatsala PG, Keshamouni VG, Padmanaban G, Rangarajan PN. Curcumin for malaria therapy. Biochem Biophys Res Commun 2005; 326(2): 472-4.
[http://dx.doi.org/10.1016/j.bbrc.2004.11.051] [PMID: 15582601]
[25]
Shishodia S, Sethi G, Aggarwal BB. Curcumin: Getting back to the roots. Ann N Y Acad Sci 2005; 1056(1): 206-17.
[http://dx.doi.org/10.1196/annals.1352.010] [PMID: 16387689]
[26]
Golonko A, Lewandowska H. Świsłocka R, Jasińska UT, Priebe W, Lewandowski W. Curcumin as tyrosine kinase inhibitor in cancer treatment. Eur J Med Chem 2019; 181: 111512.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.015] [PMID: 31404861]
[27]
Mishra B, Priyadarsini KI, Bhide MK, Kadam RM, Mohan H. Reactions of superoxide radicals with curcumin: Probable mechanisms by optical spectroscopy and EPR. Free Radic Res 2004; 38(4): 355-62.
[http://dx.doi.org/10.1080/10715760310001660259] [PMID: 15190932]
[28]
Trujillo J, Chirino YI, Molina-Jijón E, Andérica-Romero AC, Tapia E, Pedraza-Chaverrí J. Renoprotective effect of the antiox-idant curcumin: Recent findings. Redox Biol 2013; 1(1): 448-56.
[http://dx.doi.org/10.1016/j.redox.2013.09.003] [PMID: 24191240]
[29]
Wolday D, Berhe N, Akuffo H, Britton S. Leishmania-HIV in-teraction: Immunopathogenic mechanisms. Parasitol Today 1999; 15(5): 182-7.
[http://dx.doi.org/10.1016/S0169-4758(99)01431-3] [PMID: 10322351]
[30]
(a)Fouladvand M, Barazesh A, Tahmasebi R. Evaluation of in vitro antileishmanial activity of curcumin and its derivatives “gallium curcumin, Indium curcumin and diacethyle curcumin”. Eur Rev Med Pharmacol Sci 2013; 17(24): 3306-8.; (b)Santin AP, Souza AFD, Furlanetto TW. Validation of refer-ence genes for normalizing gene expression in real-time quanti-tative reverse transcription PCR in human thyroid cells in pri-mary culture treated with progesterone and estradiol. Mol Biotechnol 2013; 54(2): 278-82.; (c)de Oliveira LRC, Peresi E, de Assis Golim M, et al. Analysis of Toll-like receptors, iNOS and cytokine profiles in patients with pulmonary tuberculosis during anti-tuberculosis treatment. PLoS One 2014; 9(2): e88572.
[PMID: 24379060]
[31]
Cervantes-Valencia ME, Hermosilla C, Alcalá-Canto Y, Tapia G, Taubert A, Silva LMR. Antiparasitic efficacy of curcumin against Besnoitia besnoiti tachyzoites in vitro. Front Vet Sci 2019; 5: 333.
[http://dx.doi.org/10.3389/fvets.2018.00333] [PMID: 30687723]
[32]
Rayman MP. The importance of selenium to human health. Lancet 2000; 356(9225): 233-41.
[http://dx.doi.org/10.1016/S0140-6736(00)02490-9] [PMID: 10963212]
[33]
Pérez-Arriaga L, Mendoza-Magaña ML, Cortés-Zárate R, et al. Cytotoxic effect of curcumin on Giardia lamblia trophozoites. Acta Trop 2006; 98(2): 152-61.
[http://dx.doi.org/10.1016/j.actatropica.2006.03.005] [PMID: 16678115]
[34]
Saberi R, Fakhar M, Asfaram S, Akhtari J, Nakhaei M, Keighobadi M. A systematic literature review of curcumin with promising antileishmanial activity. Infect Disord Drug Targets 2021; 21(3): 363-9.
[http://dx.doi.org/10.2174/1871526520666200525013458]
[35]
Fattahi Bafghi A, Haghirosadat BF, Yazdian F, et al. A novel delivery of curcumin by the efficient nanoliposomal approach against Leishmania major. Prep Biochem Biotechnol 2021; 51(10): 990-7.
[http://dx.doi.org/10.1080/10826068.2021.1885045] [PMID: 34060984]
[36]
Koide T, Nose M, Ogihara Y, Yabu Y, Ohta N. Leishmanicidal effect of curcumin in vitro. Biol Pharm Bull 2002; 25(1): 131-3.
[http://dx.doi.org/10.1248/bpb.25.131] [PMID: 11824543]
[37]
Saleheen D, Ali SA, Ashfaq K, Siddiqui AA, Agha A, Yasinzai MM. Latent activity of curcumin against leishmaniasis in vitro. Biol Pharm Bull 2002; 25(3): 386-9.
[http://dx.doi.org/10.1248/bpb.25.386] [PMID: 11913540]
[38]
Das R, Roy A, Dutta N, Majumder HK. Reactive oxygen species and imbalance of calcium homeostasis contributes to curcumin induced programmed cell death in Leishmania donovani. Apoptosis 2008; 13(7): 867-82.
[http://dx.doi.org/10.1007/s10495-008-0224-7] [PMID: 18506627]
[39]
Chan MM-Y, Adapala NS, Fong D. Curcumin overcomes the inhibitory effect of nitric oxide on Leishmania. Parasitol Res 2005; 96(1): 49-56.
[http://dx.doi.org/10.1007/s00436-005-1323-9] [PMID: 15772867]
[40]
Das A, Kamran M, Ali N. HO-3867 induces ROS-dependent stress response and apoptotic cell death in Leishmania do-novani. Front Cell Infect Microbiol 2021; 11: 774899.
[http://dx.doi.org/10.3389/fcimb.2021.774899] [PMID: 34926321]
[41]
Haldar AK, Banerjee S, Naskar K, Kalita D, Islam NS, Roy S. Sub-optimal dose of sodium antimony gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania do-novani by expanding antileishmanial T-cell repertoire and in-creasing IFN-γ to IL-10 ratio. Exp Parasitol 2009; 122(2): 145-54.
[http://dx.doi.org/10.1016/j.exppara.2009.02.001] [PMID: 19422069]
[42]
Saha P, Mukhopadhyay D, Chatterjee M. Immunomodulation by chemotherapeutic agents against Leishmaniasis. Int Immunopharmacol 2011; 11(11): 1668-79.
[http://dx.doi.org/10.1016/j.intimp.2011.08.002] [PMID: 21875692]
[43]
Kolodziej H, Burmeister A, Trun W, et al. Tannins and related compounds induce nitric oxide synthase and cytokines gene expressions in Leishmania major-infected macrophage-like RAW 264.7 cells. Bioorg Med Chem 2005; 13(23): 6470-6.
[http://dx.doi.org/10.1016/j.bmc.2005.07.012] [PMID: 16143535]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy