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扭桉:化学成分分析及其芽提取物对小鼠弓形虫感染的治疗潜力。

Eucalyptus torquata: Chemical profiling and the therapeutic potential of its buds extract against Toxoplasma gondii infection in mice.

作者信息

Abdel Hamed Enas F, Said Nelly M, Drissi Badreddine, Mahdi Ismail, Abdelfattah Mohamed A O, Sobeh Mansour, Mahmoud Mona F

机构信息

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

Pathology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

出版信息

J Ethnopharmacol. 2025 Aug 29;352:120202. doi: 10.1016/j.jep.2025.120202. Epub 2025 Jun 25.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Toxoplasma gondii is a protozoan parasite that infects many warm-blooded animals, including humans. The genus Eucalyptus has been used for centuries, particularly in traditional medicine, for its antimicrobial and anti-inflammatory properties.

AIM OF THE STUDY

The phytochemical composition of Eucalyptus torquata buds extract was profiled and its potential to mitigate toxoplasmosis-related symptoms, counter histopathological insults, and inhibit cyst development in a mice model were investigated.

MATERIALS AND METHODS

HPLC-MS/MS was used to identify and annotate the phytochemical contents. Protective effects against acute and chronic toxoplasma infection were evaluated. Several biochemical parameters were tested, including AST and ALT, along with histopathological and immunohistochemistry assays. Molecular docking was utilized to pinpoint the compounds associated with the anti-toxoplasmosis activity.

RESULTS

HPLC-MS/MS analysis revealed that the plant extract contained 61 secondary metabolites belonging to various polyphenols and organic acids. Administration of E. torquata extract at 200 and 400 mg/kg/day for 14 consecutive days to mice initially infected with T. gondii ME-49 strain significantly prolonged the survival time compared to the untreated and spiramycin-treated groups. In addition, the extract, especially at 400 mg/kg, reduced the brain cyst burden (53 % and 75 %) and viability (38 % and 43 %), and decreased animals' mortality rates in both acute (48-day post-infection) and chronic (64-day post-infection) phases. Monitoring liver and renal function revealed that the extract counteracted the infection-induced damage. It significantly reduced AST, ALT, and creatinine levels and increased the serum albumin level compared to the untreated mice. Furthermore, the extract-treated mice groups showed a substantial reduction in neuron degeneration, hepatic necrosis, and the associated inflammatory signs. Immunohistochemical analyses of the cytoplasmic inducible nitric oxide synthase (iNOS) in brain and liver tissues showed that both the extract and spiramycin elicited significant decreases in iNOS expression in acute and chronic phases. Molecular docking suggested that epigallocatechin-epigallocatechin, gallic acid coumaroyl gallate, gallic acid shikimate, and galloyl diglucose had the most favorable binding affinities towards iNOS enzyme.

CONCLUSION

Altogether, these findings open a promising avenue into the potential role of E. torquata phytochemicals in managing toxoplasmosis and the related complications.

摘要

民族药理学相关性

刚地弓形虫是一种原生动物寄生虫,可感染包括人类在内的许多温血动物。桉属植物因其抗菌和抗炎特性,已被使用了几个世纪,尤其在传统医学中。

研究目的

分析了扭桉芽提取物的植物化学成分,并研究了其在小鼠模型中减轻弓形虫病相关症状、对抗组织病理学损伤以及抑制包囊形成的潜力。

材料与方法

采用高效液相色谱-串联质谱法(HPLC-MS/MS)鉴定和注释植物化学成分。评估了对急性和慢性弓形虫感染的保护作用。检测了包括谷草转氨酶(AST)和谷丙转氨酶(ALT)在内的多个生化参数,同时进行了组织病理学和免疫组织化学分析。利用分子对接确定与抗弓形虫病活性相关的化合物。

结果

HPLC-MS/MS分析表明,该植物提取物含有61种次生代谢产物,属于各种多酚和有机酸。对最初感染弓形虫ME-49株的小鼠连续14天每天给予200和400mg/kg的扭桉提取物,与未治疗组和螺旋霉素治疗组相比,显著延长了存活时间。此外,该提取物,尤其是400mg/kg剂量时,在急性(感染后48天)和慢性(感染后64天)阶段均降低了脑包囊负荷(分别降低53%和75%)和活力(分别降低38%和43%),并降低了动物死亡率。对肝肾功能的监测表明,该提取物可对抗感染引起的损伤。与未治疗的小鼠相比,它显著降低了AST、ALT和肌酐水平,并提高了血清白蛋白水平。此外,提取物治疗的小鼠组神经元变性、肝坏死及相关炎症体征明显减轻。对脑和肝组织中细胞质诱导型一氧化氮合酶(iNOS)的免疫组织化学分析表明,提取物和螺旋霉素在急性和慢性阶段均显著降低了iNOS表达。分子对接表明,表没食子儿茶素-表没食子儿茶素、香豆酰没食子酸、莽草酸没食子酸和没食子酰二葡萄糖对iNOS酶具有最有利的结合亲和力。

结论

总之,这些发现为扭桉植物化学成分在管理弓形虫病及相关并发症方面的潜在作用开辟了一条有前景的途径。

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