旋毛虫：姜黄素纳米制剂在小鼠模型中的新寄生靶点。

Trichinella spiralis: A new parasitic target for curcumin nanoformulas in mice models.

作者信息

Khedr Safaa Ibrahim, Gomaa Maha Mohamed, Mogahed Nermine Mogahed Fawzy Hussien, Gamea Ghada A, Khodear Gehan A M, Sheta Eman, Soliman Nada A H, El Saadany Amira A, Salama Amina M

机构信息

Medical Parasitology Department, Faculty of Medicine, Alexandria University, Egypt.

出版信息

Parasitol Int. 2024 Feb;98:102810. doi: 10.1016/j.parint.2023.102810. Epub 2023 Sep 18.

DOI:10.1016/j.parint.2023.102810

PMID:37730195

Abstract

Trichinosis spiralis is a global disease with significant economic impact. Albendazole is the current-treatment. Yet, the world-widely emerging antimicrobial resistance necessitates search for therapeutic substitutes. Curcumin is a natural compound with abundant therapeutic benefits. This study aimed to evaluate the potential of crude-curcumin, chitosan and for the first time curcumin-nano-emulsion and curcumin-loaded-chitosan-nanoparticles against Trichinella spiralis adults and larvae in acute and chronic trichinosis models. Trichinosis spiralis was induced in 96 Swiss-albino mice. Infected mice were divided into 2 groups. Group I constituted the acute model, where treatment started 2 h after infection for 5 successive days. Group II constituted the chronic model, where treatment started at the 30th day-post-infection and continued for 10 successive days (Refer to graphical abstract). Each group contained 8 subgroups that were designated Ia-Ih and IIa-IIh and included; a; Untreated-control, b; Albendazole-treated (Alb-treated), c; Crude-curcumin-treated (Cur-treated), d; Curcumin-nanoemulsion-treated (Cur-NE-treated), e; Albendazole and crude-curcumin-treated (Alb-Cur-treated), f; Albendazole and curcumin-nanoemulsion-treated (Alb-Cur-NE-treated), g; Chitosan-nanoparticles-treated (CS-NPs-treated) and h; Curcumin-loaded-chitosan-nanoparticles-treated (Cur-CS-NPs-treated). Additionally, six mice constituted control-uninfected group III. The effects of the used compounds on the parasite tegument, in-vivo parasitic load-worm burden, local pathology and MDA concentration in small intestines of acutely-infected and skeletal muscle of chronically-infected mice were studied. Results showed that albendazole was effective, yet, its combination with Cur-NE showed significant potentiation against adult worms and muscle larvae and alleviated the pathology in both models. Cur-CS-NPs exhibited promising results in both models. Crude-curcumin showed encouraging results especially against muscle larvae on long-term use. Treatments effectively reduced parasite load, local MDA level and CD31 expression with anti-inflammatory effect in intestine and muscle sections.

摘要

旋毛虫病是一种具有重大经济影响的全球性疾病。阿苯达唑是目前的治疗药物。然而，全球范围内不断出现的抗菌药物耐药性使得寻找治疗替代品成为必要。姜黄素是一种具有多种治疗益处的天然化合物。本研究旨在评估粗姜黄素、壳聚糖以及首次评估姜黄素纳米乳剂和载姜黄素壳聚糖纳米颗粒在急性和慢性旋毛虫病模型中对旋毛虫成虫和幼虫的治疗潜力。在96只瑞士白化小鼠中诱发旋毛虫感染。将感染小鼠分为2组。第一组构成急性模型，在感染后2小时开始治疗，连续治疗5天。第二组构成慢性模型，在感染后第30天开始治疗，并连续治疗10天（参见图形摘要）。每组包含8个亚组，分别命名为Ia - Ih和IIa - IIh，包括：a；未治疗对照组，b；阿苯达唑治疗组（阿苯达唑治疗），c；粗姜黄素治疗组（姜黄素治疗），d；姜黄素纳米乳剂治疗组（姜黄素纳米乳剂治疗），e；阿苯达唑和粗姜黄素治疗组（阿苯达唑 - 姜黄素治疗），f；阿苯达唑和姜黄素纳米乳剂治疗组（阿苯达唑 - 姜黄素纳米乳剂治疗），g；壳聚糖纳米颗粒治疗组（壳聚糖纳米颗粒治疗），h；载姜黄素壳聚糖纳米颗粒治疗组（载姜黄素壳聚糖纳米颗粒治疗）。此外，6只小鼠构成未感染对照组III。研究了所用化合物对寄生虫体表、体内寄生虫负荷（虫体负担）、局部病理学以及急性感染小鼠小肠和慢性感染小鼠骨骼肌中丙二醛浓度的影响。结果表明，阿苯达唑有效，然而，它与姜黄素纳米乳剂联合使用对成虫和肌幼虫显示出显著的增效作用，并减轻了两种模型中的病理变化。载姜黄素壳聚糖纳米颗粒在两种模型中均显示出有前景的结果。粗姜黄素显示出令人鼓舞的结果，尤其是长期使用时对肌幼虫的效果。治疗有效降低了寄生虫负荷、局部丙二醛水平和CD31表达，并在肠道和肌肉切片中具有抗炎作用。