بررسی اثر بتا‌‌آسارون بر غلظت فاکتور نکروز توموری- آلفا در مدل موش صحرایی آلزایمری‌شده

نوع مقاله : مقاله علمی پژوهشی

نویسندگان

1 دانش‌آموخته دکترای تخصصی گروه زیست شناسی، دانشکده علوم پایه، واحد علوم و تحقیقات فارس، دانشگاه آزاد اسلامی، فارس، ایران؛ دانش‌آموخته دکترای تخصصی گروه زیست شناسی، دانشکده علوم، کشاورزی و فن‌آوری‌های نوین، واحد شیراز، دانشگاه آزاد اسلامی، شیراز، ایران.

2 استاد گروه زیست شناسی، دانشکده علوم پایه، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران.

3 دانشیار گروه پاتولوژی، دانشکده علوم تخصصی دامپزشکی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران.

4 استاد گروه زیست شناسی، دانشکده علوم پایه، واحد علوم و تحقیقات فارس، دانشگاه آزاد اسلامی، فارس، ایران؛ استاد گروه زیست شناسی، دانشکده علوم، کشاورزی و فن‌آوری‌های نوین، واحد شیراز، دانشگاه آزاد اسلامی، شیراز، ایران.

5 استادیار گروه علوم پایه، دانشکده علوم تخصصی دامپزشکی، واحد علوم و تحقیقات، دانشگاه آزاد اسلامی، تهران، ایران.

چکیده

بتا­آسارون ماده موثره گیاه Acorus tatarinowii Schott می­باشد که قادر به عبور از سد خونی مغز بوده و بر سیستم اعصاب مرکزی تاثیر می­گذارد. در تحقیق حاضر اثر بتا­آسارون بر غلظت فاکتور نکروز توموری-­ آلفا (TNF-α) به­دنبال دریافت بتا­آمیلویید در مغز موش­های صحرایی نر بالغ مورد بررسی قرار گرفت. موش­های صحرایی نر بالغ به­صورت تصادفی به 9 گروه 6 تایی تقسیم شدند: گروه کنترل سالم، گروه شاهد جراحی، گروه­های دریافت­کننده بتا­آسارون (5/12، 25 و 50 میلی­گرم بر کیلوگرم وزن بدن به­صورت خوراکی به مدت 50 روز)، گروه کنترل آلزایمری (دریافت­کننده یک دوز 4 میکرولیتری بتا­آمیلویید 42-1 به­صورت تزریق دو­طرفه در هیپوکامپ) و گروه­های آلزایمری­شده و دریافت­کننده بتا­آسارون (تیمار دوزهای 5/12، 25 و 50 میلی­گرم بر کیلوگرم وزن بدن بتا­آسارون به­صورت خوراکی به مدت 30 روز و بعد از دریافت بتا­آمیلویید، ادامه تیمار با بتا­آسارون به مدت 3 هفته). در پایان آزمایش حیوانات کشته شدند و غلظت TNF-α در هموژنات مغز اندازه­گیری گردید. تیمار بتا­آسارون در دوزهای 25 و 50 میلی­گرم بر کیلوگرم وزن بدن، موجب کاهش غلظت TNF-α در موش­های صحرایی آلزایمری­شده گردید(001/0p<). با توجه به یافته­های حاصل از این مطالعه می­توان نتیجه­گیری کرد که بتا­آسارون در محافظت در برابر التهاب حاصل از دریافت بتا­آمیلویید در بافت مغز موش صحرایی نقش موثری ایفا می­کند.

کلیدواژه‌ها


عنوان مقاله [English]

Effect of Beta Asarone on concentration of TNF-α in a rat model of Alzheimer’s disease

نویسندگان [English]

  • Golshid Saki 1
  • Akram Eidi 2
  • Pejman Mortazavi 3
  • Akbar Vahdati 4
  • Negar Panahi 5
1 PhD. Graduate, Department of Biology, Faculty of Basic Science, Fars Science and Research branch, Islamic Azad University, Fars, Iran؛ PhD. Graduate, Department of Biology, Faculty of Science, Agriculture and New Technologies, Shiraz
2 Professor, Department of Biology, Faculty of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
3 - Associate Professor, Department of Pathology, Faculty of Specialized Veterinary Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.
4 Professor, Department of Biology, Faculty of Basic Science, Fars Science and Research branch, Islamic Azad University, Fars, Iran؛ Professor, Department of Biology, Faculty of Science, Agriculture and New Technologies, Shiraz Branch,
5 Assistant Professor, Department of Basic Sciences, Faculty of Specialized Veterinary Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.
چکیده [English]

Background and Purpose: β-Asarone (cis-2,4,5-trimethoxy-1-allyl phenyl), which can affect the central nervous system, is a major component of Acorus tatarinowii Schott. β-Asarone could pass the blood-brain barrier (BBB) and thus enter the brain. Pharmacological studies have demonstrated that β-asarone not only have nootropic and neuroprotective effects, but also have a cardiovascular protective effect, so we deduce that it might have cerebrovascular protection, decrease cerebral hypoperfusion and hypometabolism and treat Alzheimer’s disease (AD). Recent studies have suggested that β-asarone has anti-apoptosis activity. Moreover, β-asarone is effective against experimental models of AD, cerebral ischemia, ischemia-reperfusion-induced autophagy, oxygen-glucose deprivation, reperfusion-induced injury, and epilepsy. AD is the most common form of dementia and affects millions of people worldwide. The characteristic features associated with the AD patients include loss of memory-associated neurons, especially cholinergic neurons that result in the neurotransmitter imbalance and synaptic dysfunction. The pathophysiology of AD is associated with a variety of factors, including the extracellular deposition of insoluble -amyloid protein aggregates, forming senile plaques and intracellular accumulation of neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau proteins, oxidative neuronal damage, and inflammatory cascades. Current treatments provide only modest benefit against clinical worsening, so there is considerable interest in identifying new treatments for AD. Tumour necrosis factor α (TNF-α) inhibitors have long been used as disease-modifying agents in immune disorders. Recently, research has shown a role of chronic neuroinflammation in the pathophysiology of neurodegenerative diseases such as Alzheimer disease, and interest has been generated in the use of anti-TNF agents and TNF-modulating agents for prevention and treatment. In addition to microglial cells, another cell type implicated in the pathogenesis of AD is the astrocyte. When astrocytes are stimulated by pro-inflammatory cytokines such as interleukin-1 (IL-1) and IL-6, they become activated (reactive astrocytes) and promote inflammation through the secretion of cytokines such as TNF-α and IL-6. Of the cytokines involved in the pathogenesis of AD, TNF-α plays a central role in directing the inflammatory state in the brain and is the only cytokine shown to be consistently implicated as detrimental in AD. The levels of TNF-α in the healthy brain are low and its role is unclear under physiological conditions. In chronic inflammation, levels of TNF-α are upregulated. This makes TNF-α a valuable disease-modifying target for the treatment of AD, especially if used early in the disease process. It will be the focus of this review to describe the beneficial effect of TNF-α inhibitors on cognitive function correlated with the underlying biochemical pathology. Modulation of the TNF-α pathway led to favourable outcomes in cognitive ability in animal models. Also, the biochemical hallmarks of AD pathology such as extracellular plaque load, intracellular tau phosphorylation, and microglial and astrocyte activation were all shown to be decreased through the inhibition of the TNF-α pathway. In the present study, the effect of beta asarone on TNF-α level was investigated in β-amyloid-induced Alzheimer rats.
Materials and Methods: The adult male rats were randomly divided into 9 groups of 6: normal control, sham-operated control, β-asarone (12.5, 25, and 50 mg/kg intragastrically, daily for 50 days), Alzheimer control rats (intrahippocampal injection of β-amyloid 1-42), β-asarone (12.5, 25, and 50 mg/kg intragastrically, daily for 30 days, then induced by β-amyloid, and received the above-mentioned doses of beta asarone for 3 weeks). At the end of the experiment, the animals were anaesthetized by inhalation of diethyl ether. The entire brain was then extracted and the hippocampus was dissected and used for biochemical studies. The hippocampus was washed with chilled saline and then homogenized in chilled phosphate buffer. The homogenates were centrifuged to separate the nuclear debris. The supernatant obtained was centrifuged, which was used to assay TNF-α level by Eliza method (Diaclone, France). Data were analyzed by one-way analysis of variance followed by Tukey’s post hoc test. The criterion for statistical significance was p

کلیدواژه‌ها [English]

  • β-asarone
  • β-amyloid
  • Tumor Necrosis Factor-alpha
  • Rat
  • Alzheimer
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