An Investigation of the Cytotoxicity Effect of the Ziziphus jujuba L., Ribes khorasanicum, Crocus sativus Petal, and Centella asiatica Extracts on the NIH/3T3 Cell Line

Malaria is a life-threatening infection in the world. The emergence of strains of Plasmodium species that are resistant to anti-parasitic drugs, and the lack of licensed high-performance malaria vaccines have raised serious concerns worldwide. In recent years, new treatment strategies such as nanoformulations have been suggested as effective drug delivery systems to enhance the therapeutic efficiency of various drugs. Materials and Methods: In this study, kojic acid-solid lipid nanoparticles (KA-SLNs) and kojic acid-nanostructured lipid carriers (KA-NLCs) were synthesized using high-speed homogenization and ultra-probe sonication methods to improve their antiplasmodial activities. The obtained nanoformulations were evaluated against the Plasmodium berghei malaria parasite in mice. Anti-plasmodium activities and cytotoxicity of the nanoparticles were assed. Fifty percent effective dose (ED50) was calculated as well. Moreover, ex vivo human red blood cells (RBCs) hemolysis was assessed. Results: Kojic acid solution was significantly effective in all concentrations on the seventh day (D7) and the tenth day (D10) (P. value 0.05). The toxicity test revealed no toxic impact on the subjects. ED50 was obtained at 150 mg/kg concentration for KA-NLCs and 400 mg/kg concentration for KA-SLNs on D10. The results of the evaluation of KA nanoformulations and KA solution on RBCs indicated that KA nanoformulations could reduce the lysis of RBCs. These results also showed that the lysis of RBCs increased with raising drug concentration in KA nanoformulations, and KA-NLCs (100 mg/kg) gave the least lysis. KA nanoformulations (especially KA-NLCs) and KA solution significantly reduced parasite growth. Conclusion: These results revealed that the KA solution was safe and had no side effects on the subjects in the range of evaluated concentrations. Moreover, the results of this study showed that KA nanoformulations had abetter therapeutic effect on Plasmodium berghei in Balb/c mice compared with KA solution.