اثرات درمانی و تعدیل‌کننده ایمنی عصاره پوست انار سیاه (منشأ عراق) به‌همراه سی‌رولیموس در مدل آزمایشی کولیت اولسراتیو در موش صحرایی

نوع مقاله : مقاله پژوهشی

نویسندگان

گروه فیزیولوژی، بیوشیمی و فارماکولوژی، دانشکده دامپزشکی، دانشگاه بغداد، بغداد، عراق.

چکیده

هدف: کولیت اولسراتیو نوعی بیماری التهابی مزمن روده است که با آسیب مزمن مخاط کولون مشخص می‌شود. درمان‌های موجود عمدتاً فقط علائم بیماری را کنترل می‌کنند و درمان قطعی ارائه نمی‌دهند. هدف این مطالعه بررسی اثرات درمانی و آنتی‌اکسیدانی عصاره اتانولی پوست انار سیاه (BPPEE) به‌صورت تکی یا در ترکیب با سی‌رولیموس و مقایسه آن با درمان استاندارد سولفاسالازین در مدل کولیت القاشده با 2,4-دی‌نیتروبنزن‌سولفونیک اسید در موش صحرایی بود.
مواد و روش‌ها: موش‌ها به‌طور تصادفی به هشت گروه تقسیم شدند: گروه کنترل منفی، گروه کنترل مثبت، و گروه‌های درمانی شامل دوزهای مختلف BPPEE (200 و 300 میلی‌گرم بر کیلوگرم)، سولفاسالازین، سی‌رولیموس، و ترکیب BPPEE با سی‌رولیموس به مدت چهار هفته. میوه‌های انار سیاه در سپتامبر 2024 از باغ‌های کربلا در عراق جمع‌آوری شدند و عصاره با استفاده از اتانول 70% همراه با 1% اسید استیک تهیه گردید. عصاره دارای رنگ بنفش تیره، بافت غلیظ و چسبناک، طعم ترش و بوی معطر بود و بازده استخراج 42.5% گزارش شد. اثرات درمانی بر اساس مشاهدات بالینی، تغییرات وزن بدن، بررسی‌های بافت‌شناسی و میکروسکوپ الکترونی عبوری از بافت کولون، و اندازه‌گیری شاخص‌های استرس اکسیداتیو شامل مایلوپراکسیداز (MPO) و مالون‌دی‌آلدئید (MDA) ارزیابی شد.
نتایج: در تمامی گروه‌های تیمار شده در مقایسه با گروه کنترل مثبت، بهبود قابل‌توجهی در علائم بالینی و افزایش تدریجی وزن بدن مشاهده شد. بررسی‌های بافت‌شناسی و میکروسکوپ الکترونی نشان داد که یکپارچگی ساختار سلولی اپی‌تلیوم کولون به‌طور قابل‌توجهی بهبود یافته است، به‌ویژه در گروه‌هایی که درمان ترکیبی دریافت کردند. همچنین در این گروه‌ها کاهش معنی‌داری در سطوح MPO و MDA مشاهده شد.
نتیجه‌گیری: یافته‌های این مطالعه نشان می‌دهد که عصاره پوست انار سیاه دارای خواص ضدالتهابی و آنتی‌اکسیدانی است. همچنین استفاده همزمان از این عصاره با سی‌رولیموس اثر هم‌افزایی قابل‌توجهی در بهبود شاخص‌های بالینی، بافتی و بیوشیمیایی در مدل کولیت اولسراتیو دارد. بنابراین، این ترکیب می‌تواند به‌عنوان یک رویکرد امیدوارکننده در مدیریت کولیت اولسراتیو مطرح شود.

کلیدواژه‌ها


عنوان مقاله [English]

The therapeutic and immunomodulatory effects of black pomegranate peel extract (from Iraq) plus to sirolimus in an experimental rat’s model of ulcerative colitis

نویسندگان [English]

  • Sarah S. Abdel Abbas
  • Falah M. K. AL-Rekabi
Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Baghdad, Baghdad, Iraq.
چکیده [English]

Objective
Ulcerative colitis is a chronic type of inflammatory bowel disease that is characterized by chronic colonic mucosa injury. Current treatments for the disease only provide symptomatic management rather than a cure. The present study aimed to investigate the therapeutic and antioxidant effects of ethanolic black pomegranate peel extract (BPPEE) used as monotherapy or in combination with sirolimus and compare the effects to those of standard sulfasalazine treatment in the 2,4-dinitrobenzenesulfonic acid-induced colitis rat model.
Materials and methods
Rats were randomly divided into eight groups: a negative control group, a positive control group, and treatment groups with different doses of BPPEE (200 and 300 mg/kg), sulfasalazine, and sirolimus, and the combination of BPPEE and sirolimus, for four weeks. Black pomegranate fruits were collected from Karbala orchards in Iraq in September 2024, and the extract was formulated using 70% ethanol supplemented with 1% acetic acid of this fruit. The extract was characterized by physical features of dark purple in color, thick and viscous nature, sour in taste, and aromatic smell, with the extraction yield being 42.5%. Therapeutic effects were determined on the basis of clinical observation, changes in body weight, histological and transmission electron microscopy study of colon tissues and the measurement of oxidative stress markers including myeloperoxidase and malondialdehyde.
Results
There was a marked improvement in clinical signs and a gradual recovery of body weight in all treated groups compared to the positive control group. The histological and electron microscopy analyses showed that there was a marked improvement in the integrity of the cellular structure of the colonic epithelium in comparison to the positive control group, especially in those animals treated with the combination therapy. Moreover, these two groups showed a marked decrease in myeloid peroxidase (MPO) and myelondylaldehyde (MDA) levels.
Conclusion
These findings show that the black pomegranate peel extract has anti-inflammatory and antioxidant properties. Moreover, the use of the black pomegranate peel extract in conjunction with sirolimus has shown a significant synergistic effect in the improvement of clinical, histological, and biochemical parameters in the ulcerative colitis model. Thus, the use of the black pomegranate peel extract in conjunction with sirolimus could be regarded as a promising approach in the management of ulcerative colitis.

کلیدواژه‌ها [English]

  • black pomegranate peel extract
  • inflammatory bowel disease
  • rat
  • therapeutic effects
  • ulcerative colitis
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