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通过调节白细胞介素、环氧化酶和肿瘤坏死因子-α,非洲菊在神经元脱髓鞘大鼠模型中的神经保护潜力。

The neuroprotective potential of Gerbera Jamesonii in a neuronal demyelination rat model through the modulation of interleukins, cyclooxygenase and tumor necrosis factor-α.

作者信息

Bukhari Shazia Anwer, Sadia Haleema, Chauhdary Zunera

机构信息

Department of Biochemistry, Government College University Faisalabad, , Faisalabad, Pakistan.

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan.

出版信息

Inflammopharmacology. 2025 Apr 17. doi: 10.1007/s10787-025-01742-w.

Abstract

Multiple sclerosis is characterized by the demyelination of neurons, which is a chronic inflammatory disease of the central nervous system. This autoimmune disorder occurs due to an imbalance in the body's immune system as a result of uncontrolled oxidative stress. The B and T lymphocytes cross the blood-brain barrier and destroy the myelin sheath. Multiple sclerosis is one of the most common causes of disability in young adults affecting approximately 3 million individuals worldwide. Among them, females are considered at higher risk than males. It disrupts the normal functioning of life badly and major symptoms include loss of sensation, poor vision, impaired hearing, and cognitive abnormalities. Several treatments and drugs have been used to treat this medical condition, but they pose serious side effects also. So, the need of the hour is to explore such natural bioactive compounds that have neuroprotective properties, thus leading to the treatment of neurodegenerative disorders. Among various plants with medicinal properties, Gerbera jamesonii is a plant that exhibits antioxidant, anti-inflammatory, and neuroprotective properties. To enhance its therapeutic potential, this study aimed to load its ethanolic extract into solid-lipid nanoparticle formulations (SLNs), which is an innovative approach for treatment because nanoparticles provide effective targeted drug delivery due to their extremely small size. Solid-lipid nanoparticles were prepared using the emulsification-solvent evaporation method. For experimental design, 30 Wistar rats were randomly divided into seven groups (n = 10): normal, demyelination disease model, standard drugs, dimethyl fumarate and fingolimod (FTY 720) 15 mg/kg, and three treatment groups: GJ-NPs 250 mg/kg, 500 mg/kg, and 750 mg/kg. Prior to treatment, 0.2% cuprizone solution was prepared for the induction of multiple sclerosis in all groups except the normal group for 42 days. Biochemical analyses such as determination of inflammatory biomarkers and antioxidant enzymes were performed. The plant extract was subjected to HPLC to examine its phenolic compounds which are active in healing neurodegeneration. Physiological changes in rats were observed such as motor dysfunction and anxiety-like behavior caused by cuprizone. Behavioral tests showed significant improvement of motor function, muscular coordination, and enhanced cognitive abilities in the treatment groups as compared to the demyelination disease model. Histopathology of the rat brain regions showed significant differences in the normal and demyelinated areas. The results showed that GJ-NPs treated demyelination, modulating oxidative stress manifested by pro-inflammatory cytokines TNF-α, IL-6, AβPP, α-synuclein, NF-B, etc., thus restoring the levels of antioxidant enzymes to normal range.

摘要

多发性硬化症的特征是神经元脱髓鞘,它是一种中枢神经系统的慢性炎症性疾病。这种自身免疫性疾病是由于体内免疫系统失衡,这是由不受控制的氧化应激导致的。B淋巴细胞和T淋巴细胞穿过血脑屏障并破坏髓鞘。多发性硬化症是年轻成年人中最常见的致残原因之一,全球约有300万人受其影响。其中,女性被认为比男性风险更高。它严重扰乱了正常的生活功能,主要症状包括感觉丧失、视力不佳、听力受损和认知异常。已经使用了几种治疗方法和药物来治疗这种疾病,但它们也会带来严重的副作用。因此,当务之急是探索具有神经保护特性的天然生物活性化合物,从而治疗神经退行性疾病。在各种具有药用特性的植物中,非洲菊是一种具有抗氧化、抗炎和神经保护特性的植物。为了提高其治疗潜力,本研究旨在将其乙醇提取物负载到固体脂质纳米粒制剂(SLNs)中,这是一种创新的治疗方法,因为纳米粒由于其极小的尺寸提供了有效的靶向药物递送。采用乳化溶剂蒸发法制备固体脂质纳米粒。在实验设计中,将30只Wistar大鼠随机分为七组(n = 10):正常组、脱髓鞘疾病模型组、标准药物组、富马酸二甲酯和芬戈莫德(FTY 720)15mg/kg组,以及三个治疗组:GJ-NPs 250mg/kg组、500mg/kg组和750mg/kg组。在治疗前,除正常组外,为所有组制备0.2%的铜螯合剂溶液以诱导多发性硬化症,持续42天。进行了生化分析,如测定炎症生物标志物和抗氧化酶。对植物提取物进行高效液相色谱分析,以检测其对治疗神经退行性变有活性的酚类化合物。观察大鼠的生理变化,如由铜螯合剂引起的运动功能障碍和焦虑样行为。行为测试表明,与脱髓鞘疾病模型组相比,治疗组的运动功能、肌肉协调性有显著改善,认知能力增强。大鼠脑区的组织病理学显示正常区域和脱髓鞘区域有显著差异。结果表明,GJ-NPs治疗脱髓鞘,调节由促炎细胞因子TNF-α、IL-6、AβPP、α-突触核蛋白、NF-κB等表现出的氧化应激,从而将抗氧化酶水平恢复到正常范围。

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