Cytotoxic and Immunomodulatory Activity of Curcumin and Chitosan on Experimental Toxoplasmosis

Mahsa   Rezgi; Elham  Yousefi; Behzad  Jafari; Negar  Asadi; Shahram  Khademvatan; Gordon  S Howarth

doi:10.18502/ijpa.v19i2.15858

Mahsa Rezgi Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia, Iran
Elham Yousefi Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia, Iran
Behzad Jafari Department of Medicinal Chemistry, School of Pharmacy Urmia University of Medical Sciences, Urmia, Iran
Negar Asadi Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia, Iran
Shahram Khademvatan Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia, Iran
Gordon S Howarth School of Animal and Veterinary Sciences, Roseworthy Campus, University of Adelaide, South Australia

DOI: https://doi.org/10.18502/ijpa.v19i2.15858

Keywords: Toxoplasma gondii; Curcumin; Chitosan; In silico

Abstract

Background: Toxoplasma gondii is a pathogenic parasite with worldwide distribution. We investigated curcumin and chitosan in combination on the viability of T. gondii tachyzoites in silico, in vitro and in vivo.

Methods: A 3D model was employed in Urmia University of Medical Sciences, Urmia, Iran in 2021 to study the interaction between curcumin and dihydrofolate reductase (DHFR). Ramachandran root-mean-square deviation and VERIFY3D validated the model. Cytotoxicity of curcumin and chitosan was evaluated by MTT viability assay. BALB/c mice infected with 10⁴Toxoplasma organisms were treated with curcumin, chitosan, and the combination of curcumin+chitosan. Serum levels of inducible NO synthetase (iNOs), interferon gamma (IFN-γ), interleukin (IL)-5, glutamate oxaloacetic transaminases(SGOT), and glutamic pyruvate transaminase (SGPT) were determined.

Result: Curcumin-DHFR and curcumin-DHPS (dihydropteroate synthase) interactions and calculated enzyme energy indicated an excellent affinity for curcumin with DHFR, but not DHPS. MTT results of concurrent treatments demonstrated IC₅₀rates of 0.1, 0.05, and 0.01 mg/ml at 24, 48, and 72h, respectively. IFN-γ, IL-5 and iNOs levels in curcumin+chitosan treated mice were 1.71, 0.51, and 1.51 IU/L, while those of SGOT and SGPT were 76 and 84 IU/L, respectively.

Conclusion: The combination of curcumin and chitosan increased survival time of infected mice by seven days. Curcumin and chitosan in combination regulated the immune system and reduced liver damage, potentially forming the basis of a new treatment for toxoplasmosis.