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Preparation,formulation, and chemical characterization of silver nanoparticles using Melissa officinalis leaf aqueous extract for the treatment of acute myeloid leukemia in vitro and in vivo conditions
Authors:Ahmad Ahmeda  Akram Zangeneh  Mohammad Mahdi Zangeneh
Institution:1. Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar;2. Department of Clinical Sciences, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran
Abstract:The demand for nanoparticles is increasing day by day due to their wide range of applications in various areas including pharmaceutical industry. Nanoparticles are formally synthesized by chemical methods in which the toxic and flammable chemicals are used. Synthesis of nanoparticles from various biological systems has been reported, but among all, biosynthesis of nanoparticles from plants is considered as the most suitable method. The current study confirms the potential of aqueous extract of Melissa officinalis grown under in vitro condition for the green synthesis of silver nanoparticles (AgNPs). Also, we revealed the cytotoxicity, antioxidant, and anti-acute myeloid leukemia effects of AgNPs compared to mitoxantrone in a leukemic mouse model. The synthesized AgNPs were characterized using several techniques including UV–Vis., FT-IR, TEM, FE-SEM, and EDS. In vivo experiment, induction of acute myeloid leukemia was done by DMBA in 75 mice. The obtained results were fed into SPSS-22 software and analyzed by one-way ANOVA. By quantitative real-time PCR, S1PR1 and S1PR5 mRNA expression in lymphocytes were significantly (p ≤ 0.01) increased by treating the leukemic mice with the AgNPs and mitoxantrone. Also, AgNPs similar to mitoxantrone, significantly (p ≤ 0.01) enhanced the platelet, lymphocyte, and RBC parameters and the anti-inflammatory cytokines (IL4, IL5, IL10, IL13, and IFNα) and reduced the total WBC, blast, monocyte, neutrophil, eosinophil, and basophil counts and the pro-inflammatory cytokines (IL1, IL6, IL12, IL18, IFNY, and TNFα) as compared to the untreated mice. In vitro experiment, AgNPs similar to mitoxantrone had low cell viability dose-dependently against murine C1498, human HL-60/vcr, and 32D-FLT3-ITD cell lines without any cytotoxicity on HUVEC cell line. Furthermore, the DPPH assay showed similar antioxidant potentials for AgNPs and mitoxantrone. Above results approve the excellent anti-acute myeloid leukemia, cytotoxicity, and antioxidant properties of AgNPs compared to mitoxantrone.
Keywords:acute myeloid leukemia  chemotherapeutic drug  Melissa officinalis  mitoxantrone  silver nanoparticles
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