Stigmasterol attenuates cuprizone-induced neuroinflammation and demyelination in rats through modulation of inflammatory mediators and oxidative stress.

IF 6.3 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2026-10-05 DOI:10.1007/s10787-026-02411-2

Rabeea Safdar, Uzma Saleem

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引用次数: 0

Abstract

Purpose: Multiple sclerosis is a neuroinflammatory and demyelinating condition of brain with limited therapeutic options, many of which are associated with high treatment costs and adverse effects, In this research work, the neuroprotective potential of stigmasterol was investigated in a rat model of cuprizone-induced neuroinflammation and demyelination.

Materials and methods: A total of 36 Wistar rats (150-200 g) of both sexes were divided into 6 groups (n = 6) in random manner. Neuroinflammation and demyelination were induced by feeding animals a 0.3% cuprizone-containing diet for 5 weeks. Stigmasterol (100, 200, or 400 mg/kg/day) or dimethyl fumarate (15 mg/kg/day) was then administered orally for 3 weeks while cuprizone administration continued. After behavioral analysis, oxidative stress biomarkers, neurotransmitter levels, myelin-basic protein concentration by ELISA, mRNA expression of myelin basic protein and inflammatory cytokines, and histopathological alternations were evaluated.

Results: Cuprizone administration pointedly increased oxidative stress, impaired behavioral performances, induced marked histopathological alterations, reduced mRNA expression of MBP and the anti-inflammatory cytokines, and elevated expression of inflammatory cytokines. Compared with cuprizone group, stigmasterol treatment prominently improved cognitive and locomotor performance (P < 0.001), restored antioxidant status (P < 0.001), upregulated the mRNA expression of IL-4, IL-10 and MBP, downregulated expression of IL-1β, TNF-α and IL-6, and increased both neurotransmitter concentrations (P < 0.001) and MBP concentrations in a dose-dependent manner. The effects of dimethyl fumarate were comparable to those observed with the highest dose of stigmasterol.

Conclusion: Stigmasterol alleviated cuprizone-induced neuroinflammation, demyelination, oxidative stress and behavioral deficits while restoring MBP expression and modulating inflammatory cytokines expression. These results suggest that stigmasterol possesses neuroprotective and anti-inflammatory properties and warrants further investigation as an effective therapeutic candidate for demyelinating and neuroinflammatory disorders.

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豆甾醇通过调节炎症介质和氧化应激减轻铜酮诱导的大鼠神经炎症和脱髓鞘。

目的：多发性硬化症是一种大脑神经炎症和脱髓鞘疾病，治疗方法有限，其中许多治疗费用高，副作用大。本研究在铜酮诱导的神经炎症和脱髓鞘大鼠模型中研究了名豆甾醇的神经保护潜力。材料与方法：取两性Wistar大鼠36只（150 ~ 200 g），随机分为6组（n = 6）。用含0.3%铜酮的日粮喂养动物5周，诱导神经炎症和脱髓鞘。然后口服豆甾醇（100、200或400 mg/kg/天）或富马酸二甲酯（15 mg/kg/天）3周，同时继续服用铜吡酮。行为分析后，评估氧化应激生物标志物、神经递质水平、ELISA测定的髓鞘碱性蛋白浓度、髓鞘碱性蛋白和炎症因子mRNA表达以及组织病理学改变。结果：给药铜普利酮可明显增加大鼠的氧化应激，行为表现受损，引起明显的组织病理学改变，MBP和抗炎细胞因子mRNA表达降低，炎症细胞因子表达升高。结论：豆甾醇可减轻铜普利酮诱导的神经炎症、脱髓鞘、氧化应激和行为缺陷，恢复MBP表达，调节炎症因子表达。这些结果表明，豆甾醇具有神经保护和抗炎特性，值得进一步研究作为脱髓鞘和神经炎症疾病的有效治疗候选者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]