Rezgi Mahsa, Yousefi Elham, Jafari Behzad, Asadi Negar, Khademvatan Shahram, Howarth Gordon S
Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia, Iran.
Department of Medical Parasitology and Mycology, Urmia University of Medical Sciences, Urmia, Iran.
Iran J Parasitol. 2024 Apr-Jun;19(2):224-237. doi: 10.18502/ijpa.v19i2.15858.
is a pathogenic parasite with worldwide distribution. We investigated curcumin and chitosan in combination on the viability of tachyzoites in silico, in vitro and in vivo.
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 104 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.
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 IC rates 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.
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.
是一种分布于全球的致病性寄生虫。我们在计算机模拟、体外和体内研究了姜黄素和壳聚糖联合使用对速殖子活力的影响。
2021年在伊朗乌尔米亚医科大学采用三维模型研究姜黄素与二氢叶酸还原酶(DHFR)之间的相互作用。采用拉马钱德兰均方根偏差和VERIFY3D对模型进行验证。通过MTT活力测定评估姜黄素和壳聚糖的细胞毒性。用姜黄素、壳聚糖以及姜黄素+壳聚糖联合治疗感染104个生物体的BALB/c小鼠。测定血清中诱导型一氧化氮合酶(iNOs)、干扰素γ(IFN-γ)、白细胞介素(IL)-5、谷氨酸草酰乙酸转氨酶(SGOT)和谷氨酸丙酮酸转氨酶(SGPT)的水平。
姜黄素-DHFR和姜黄素-DHPS(二氢蝶酸合酶)相互作用以及计算得到的酶能量表明,姜黄素与DHFR具有良好的亲和力,但与DHPS没有。联合处理的MTT结果显示,在24、48和72小时时的IC50分别为0.1、0.05和0.01mg/ml。姜黄素+壳聚糖处理的小鼠中,IFN-γ、IL-5和iNOs水平分别为1.71、0.51和1.51IU/L,而SGOT和SGPT水平分别为76和84IU/L。
姜黄素和壳聚糖联合使用使感染小鼠的存活时间延长了7天。姜黄素和壳聚糖联合调节免疫系统并减轻肝脏损伤,可能为弓形虫病的新治疗方法奠定基础。