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عضویت

جستجوی مقالات مرتبط با کلیدواژه « ellagic acid » در نشریات گروه « پزشکی »

  • Ali Kargar, Fatemeh Mohammadi, Mehran Amirizadeh, Negin Hallajbashi, Fatemeh Kargar, Hamidreza Mohammadi *
    Background

     Cholemic nephropathy (CN), a renal dysfunction caused by bile acids, is a severe complication of chronic liver damage and bile duct ligation (BDL), which may lead to complete kidney failure.

    Objectives

     This study investigated the protective effect of ellagic acid on CN in cholestatic rats.

    Methods

     Sixty male Wistar rats weighing about 180 - 200 g were randomly divided into 6 groups for in vivo investigation. The rats were randomly divided into 5 groups of 10. Cholestasis was induced in rats by closing the bile ducts; then, the animals were treated with different doses of ellagic acid (10, 25, and 50 mg/kg). Then, the induction effect of cholestasis and the protective effects of ellagic acid on serum and urinary factors, oxidative stress indices, and histopathological changes in liver and kidney tissue were investigated.

    Results

     Bile duct ligation in rats led to an increase in serum and urinary factors. It was also associated with increased reactive oxygen species (ROS), lipid peroxidation, glutathione (GSH) oxide form, decrease in antioxidant systems, GSH and severe histopathological changes, and fibrosis of the liver and kidney tissues. Another finding of this research was the beneficial effect of ellagic acid in improving serum and urinary factors, oxidative stress indices, and histopathological changes.

    Conclusions

     Due to its antioxidant properties, ellagic acid can potentially serve as a novel therapeutic approach for treating kidney damage caused by increased serum levels of bile acids.

    Keywords: Ellagic Acid, Oxidative Stress Indicators, Rats, Bile Duct Ligation}
  • Somayeh Sheikh, Hesam Dehghani, Hamid Kazerani *
    Objective
    There is escalating evidence suggesting the beneficial effects of ellagic acid (EA) on the cardiovascular system. The aim of the present study was to investigate the protective effect of EA in human umbilical vein endothelial cells (HUVECs) against high glucose (HG)- induced endothelial dysfunction and to study the potential roles of adropin and nitric oxide (NO) in this regard.
    Materials and Methods
    The experimental groups consisted of normal and HG (30 mM, 48 hr)-treated HUVECs incubated without or with 5 or 10 μM of EA (6 groups of at least 6 replicates, each). The cell count and viability were studied. Moreover, the markers of the redox state, including malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and catalase enzymes, and ferric reducing anti-oxidant power (FRAP), were assayed. The levels of adropin and eNOS gene expression were also studied using RT-qPCR.
    Results
    A high concentration of glucose reduced cell count and caused lipid peroxidation, reduced anti-oxidant capacity of the cells, decreased NO levels, and downregulated the expression of NOS3 (encoding eNOS) and ENHO (encoding adropin) genes. Ellagic acid reversed all these effects.
    Conclusion
    These results suggest a significant protective effect for EA against HG-induced injury in HUVECs. The improved redox state and upregulation of NOS3 and ENHO genes seem to play critical roles in this regard.
    Keywords: Endothelial dysfunction, Ellagic acid, Adropin, Antioxidant, Hyperglycemia}
  • Khadijeh Hassonizadeh Falahieh, Alireza Sarkaki *, Mohammadamin Edalatmanesh, Mohammad Kazem Gharib Naseri, Yaghoob Farbood
    Objective
    Cerebral ischemia/reperfusion (I/R) has been known as a major cause of inability and mortality worldwide. Ellagic acid (EA) has many pharmacological effects including antioxidant, antithrombotic and neurorestoration activities. The aim of this study was evaluation of the effects of EA on motor and cognitive behaviors, hippocampal local field potential (LFP), brain oxidative stress in male rats with cerebral 2-vessel occlusion ischemia/reperfusion (2VO I/R).
    Materials and Methods
    Forty-eight male Wistar rats (250-300 g) were assigned into six groups. 1) The Sham: rats were treated with DMSO10%/normal saline as solvent of EA 3 times daily for 1 week; 2) I/R+Veh; I/R rats received vehicle; 3-5) EA-treated groups: I/R rats received 50, 75, or 100 mg/kg EA; and 6) Cont+EA100: intact rats received EA. The cerebral 2VO I/R was made by the bilateral common carotid arteries closing for 20 min followed by reperfusion. The behavioral tests and hippocampal LFP recording were performed after treatment with EA. The oxidative stress parameters were assayed by special ELISA kits.
    Results
    Cerebral 2VO I/R significantly decreased motor coordination, memory and hippocampal LFP and significantly increased oxidative stress. Treatment with EA improved all I/R complications. 
    Conclusion
    The current findings showed that treatment of I/R rats with EA could reverse cognitive and motor functions, and improve the LFP and oxidative stress markers. So, effects of EA on cognitive and motor function may at least in part, be due to its antioxidative actions.
    Keywords: Cerebral ischemia, reperfusion, Ellagic acid, Motor coordination, Cognition, Hippocampal local EEG, Oxidative stress}
  • آفرین جودکی نژاد، حمیدرضا محمدی*، محسن محمدی، فرهاد مومنی، احمد آدینه
    سابقه و هدف

    الاژیک اسید یک ترکیب پلی فنولی طبیعی با خاصیت آنتی اکسیدان بالقوه است که در بیش تر میوه ها، دانه ها و سبزیجات وجود دارد. در این مطالعه اثرات تجویز الاژیک اسید در مدل آسیب کبدی ناشی از تیواستامید در موش های صحرایی مورد بررسی قرار گرفت.

    مواد و روش ها

    برای انجام این مطالعه تجربی تعداد 60 سر موش صحرایی نر نژاد ویستار با وزن تقریبی 200گرم، به طور تصادفی به 6 گروه 10 تایی تقسیم شدند. آسیب کبدی با تجویز mg/kg 100 تیواستامید در سه روز متوالی به صورت تک دوز ایجاد شد. سپس دوزهای مختلف الاژیک اسید (10، 25 و50 میلی گرم بر کیلوگرم) به مدت سه روز متوالی به صورت تک دوز به موش های بیمار تجویز شد. در نهایت 24 ساعت پس از آخرین تزریق، فاکتورهای بیوشیمیایی (ALP، AST ALT، LDH، بیلی روبین و پروتیین تام)، مارکرهای استرس اکسیداتیو (LPO،ROS ،FRAP،GSH)، غلظت یون آمونیوم و فعالیت حرکتی موش ها مورد بررسی قرار گرفت. برای تجزیه و تحلیل آماری از آزمون تحلیل واریانس یک طرفه و آزمون تعقیبی توکی استفاده شد.

    یافته ها

    تیواستامید منجر به آسیب کبدی شد که خود را به صورت افزایش معنی دار فاکتورهای بیوشیمیایی سرم و مارکرهای استرس اکسیداتیو نشان داد(0/05>P). علاوه بر این میزان یون آمونیوم در پلاسما، به عنوان فاکتور کلیدی موثر در انسفالوپاتی کبدی، در حیوانات دریافت کننده تیواستامید به میزان بسیار زیادی افزایش داشت(0/05>P). تجویز الاژیک اسید در دوزهای مختلف به طور چشمگیری آسیب های کبدی و غلظت آمونیوم پلاسما را کاهش داد(0/05>P).

    استنتاج

    نتایج مطالعه حاضر نشان می دهد که الاژیک اسید از طریق فعالیت های آنتی اکسیدانی موجب کاهش آسیب کبدی ناشی از تیواستامید می شود.

    کلید واژگان: تیواستامید, آسیب کبدی, آمونیوم پلاسما, الاژیک اسید, استرس اکسیداتیو}
    Afarin Joudaki Nezhad, Hamidreza Mohammadi*, Farhad Momeni, Morteza Amraei, Ahmad Adineh

    Background and

    purpose

    Ellagic acid is a natural polyphenol compound with potential antioxidant properties that is present in most fruits, seeds, and vegetables. Therefore, this study was designed to investigate the effects of ellagic acid administration on the liver damage model caused by thioacetamide in rats.

    Materials and methods

    In this experimental study, 60 male Wistar rats weighing approximately 200 grams were randomly divided into six groups (n=10). Liver damage was caused by a single dose (100 mg/kg) administration of thioacetamide for three consecutive days. Different doses of ellagic acid (10, 25 and 50 mg/kg) were administered to the sick mice as a single dose for three consecutive days. Finally, 24 hours after the last injection, biochemical factors (ALP, AST, ALT, LDH, bilirubin, total protein), oxidative stress markers (LPO, ROS, FRAP, GSH), ammonium ion concentration, and movement activity of the mice were examined. One-way analysis of variance and Tukey's post hoc test were used for statistical analysis.

    Results

    Thioacetamide led to a significant increase in serum biochemical factors and oxidative stress markers in the studied groups (P<0.05). In addition, the amount of ammonium ion in the plasma, as a key effective factor in hepatic encephalopathy, was greatly increased in animals receiving thioacetamide (P<0.05). Administration of ellagic acid in different doses significantly reduced liver damage and plasma ammonium concentration (P<0.05).

    Conclusion

    The results of this study showed that ellagic acid reduced liver damage caused by thioacetamide through its antioxidant activities.

    Keywords: thioacetamide, liver damage, plasma ammonium, ellagic acid, oxidative stress}
  • مرجان منصوری دارا، نیلوفر رجایی قاسم قشلاقی، فائزه حیدری، فرشاد غزالیان*، سحر ابراهیمی، روشن عسکری، فرجام راشدی

    زمینه و هدف:

     چاقی از مه مترین دغدغ ه ها و مشکلات تهدیدکننده سلامتی در سرتاسر جهان است و فعالیت ورزشی و رژیم غذایی سالم از مهمترین را ه های درمان و پیشگیری از آن می باشند. بنابراین، هدف از اجرای تحقیق بررسی تاثیر 12 هفته تمرین تناوبی شدید همراهبا مکم لسازی اسید الاژیک بر شرایط اکسیدانی/آنتی اکسیدانی زنان چاق بود.

    روش بررسی:

     بدین منظور 56 نفر از زنان چاق به 4 گروه تمرین ورزشی تناوبی شدید، گروه مکم لدهی اسید الاژیک، گروه تمرین ورزشی تناوبی شدید+گروه مکم لدهی اسید الاژیک و گروه دارونما تقسیم شدند. اگدننکتکرشن گروه تمرین ورزشی تناوبی شدید به مدت 12هفته، تمرین مورد نظر را به صورت 4 وهله 4 دقیق های دویدن اینتروال در 85 - 95 درصد ضربان قلب بیشینه که با 3 دقیقه دویدن با شدت 60-50 درصد ضربان قلب بیشینه و 7 دقیقه استراحت بین تناوب ها همراه بود، انجام دادند. همچنین مکمل دهی اسید الاژیک به صورتیک کپسول 50 میل یگرمی/روز مصرف شد. نمون ه های خونی قبل از انجام مداخله و 48 ساعت پس از آخرین جلسه تمرینی 12 هفته تمرین ورزشی تناوبی شدید برای برسی سطوح سرمی مالون دی آلدهید، گلوتاتیون پراکسیداز و ظرفیت آنتی اکسیدانی تام انجام شد.

    یافته ها:

     بین مقادیر مالو ند یآلدهید و ظرفیت آنت یاکسیدان تام آزمودن یها در گرو ه های مورد مطالعه پس از 12 هفته تمرین ورزشیتناوبی شدید همراه با مصرف مکم لدهی اسید الاژیک تفاوت معناداری وجود دارد(0001 / P=0) و این تفاوت بین گروه ترکیبی تمرین ورزشی تناوبی شدید+ مکم لدهی اسید الاژیک با دیگر گرو ه ها بوده است.

    نتیجه  گیری:

     یافته های مطالعه حاضر نشان داد انجام تمرین تناوبی شدید همراه با مکم لدهی اسید الاژیک سبب بهبود عوامل آنتیاکسیدانی و اکسیدانی زنان چاق م یشود. هر چند که انجام تمرینات شدید نتایجی بهتری نسبت به مکمل داشت.

    کلید واژگان: چاقی, استرس اکسیداتیو, اسید الاژیک, تمرین تناوبی شدید}
    Marjan Mansouridara, Niloofar Rajai Ghasemgheshlagi, Faeze Heydari, Farshad Ghazalian *, Sahar Ebrahimi, Roshan Askari, Farjam Rashedi
    Background and Objectives

    Obesity is one of the most important concerns and problems that threatenhealth all over the world, and sports activity and healthy diet are the most important ways to treat andprevent it. so, this study aims to evaluate the effect of 12 weeks of high-intensity interval training (HIIT)and Ellagic Acid (EA) supplementation on oxidative/antioxidant markers in obese women.

    Subjects and Methods

    In this randomized clinical trial, 56 inactive obese women were randomly dividedinto four groups of HIIT, EA, EA+HIIT, and Control. The HIIT groups performed the training for 12 weeksincluding four 4-minute interval running at 85-95% HRpeak, 3 minutes of running at 50-60% HRpeak and7 minutes of rest interval. EA supplement was administered at a dose of 50 mg/day for 12 weeks. Bloodsamples were collected from the subjects before and 48 hours after the last session to assess serumlevels of glutathione peroxidase (GPx), Malondialdehyde (MDA), and total antioxidant capacity (TAC).

    Results 

    There was a significant difference between EA+HIIT and HIIT groups in MDA (P=0.005), TAC(P=0.003) and GPx (P=0.0001) after intervention. There was a significant difference between the MDAand TAC values of the subjects in the studied groups after 12 weeks of HIIT with EA supplementation(P=0.0001). And this was the difference between the combined group (EA+HIIT) and other groups.

    Conclusion

    Twelve weeks of HIIT and EA supplementation can significantly improve antioxidant and oxidantfactors in obese women.

    Keywords: Obesity, oxidative stress, ellagic acid, high intensity interval training}
  • Mehran Mohammadi, Zahra Boghrati, Seyed Ahmad Emami, Maryam Akaberi *

    In the great Persian Empire, pomegranate (Punica granatum L.) had a wide reputation for use both as an herbal medicine and nutritious food. It was also a symbol of peace and love according to Achaemenid limestones in the great Persia. This paper aims to review the traditional uses of pomegranate in Persian and Islamic traditional medicine and have thorough and current information regarding the pharmacology and phytochemistry of this valuable plant for practical use and further research. Relevant information about P. granatum was collected from scientific publishers and databases including Elsevier, Wiley, PubMed, and Google Scholar between 1950 and 2022. The traditional knowledge was extracted from Persian and Islamic traditional textbooks. Based on traditional textbooks, pomegranate has beneficial effects on diseases related to gastrointestinal, upper and lower respiratory, visual, and reproductive systems. In addition, pomegranate and its preparations have been prescribed for treating metabolic disorders, skin problems, and wounds as well as dental protection. Preclinical and clinical evidence supports many therapeutic potentials of pomegranate in traditional medicine. Its therapeutic effects are mostly attributed to its polyphenols. The knowledge in Persian and Islamic traditional textbooks about pomegranate and its preparations can be used as a guide for further preclinical and mainly clinical studies to discover the therapeutic potential of this valuable plant.

    Keywords: Ellagic acid, Ethnopharmacology, Persian Traditional Medicine, Pomegranate, Punica granatum}
  • صفورا رئوفی*، عبدالرحمن صریحی، علیرضا کمکی، سیامک شهیدی
    مقدمه و هدف
    دیابت ملیتوس با اختلال حافظه همراه است. الاژیک اسید (EA) پلی فنولی طبیعی با اثرات ضددیابتی و حفاظت کننده عصبی است. هدف مطالعه حاضر بررسی اثر حفاظتی الاژیک اسید بر اختلال حافظه ناشی از دیابت و ارزیابی نقش اثر ضداسترس اکسیداتیو این ترکیب بود.
    مواد و روش ها
    موش های بزرگ آزمایشگاهی نر، نژاد ویستار به طور تصادفی به چهار گروه (n=8) کنترل، دیابتی، دیابتی دریافت کننده دوز 25 mg/kg EA  و دیابتی دریافت کننده دوز50 mg/kg  EA تقسیم شدند. دیابت به وسیله تزریق داخل صفاقی تک دوز 60 mg/kg از استرپتوزوتوسین (STZ) القا شد. پس از 4 هفته دریافت داخل معده ای (گاواژ) EA (یک بار در روز)، بررسی حافظه توسط تست حافظه احترازی غیرفعال (PAL) انجام شد. در انتها فاکتورهای مرتبط با استرس اکسیداتیو شامل مالون دی آلدیید (MDA) و ظرفیت آنتی اکسیدانی تام (TAC) در بافت هیپوکامپ که تحت بیهوشی عمیق از مغز حیوانات جدا شد ارزیابی شدند.
    نتایج
    حیوانات دیابتیک به صورت قابل توجه کاهش زمان تاخیر در ورود به قسمت تاریک (STLr) و افزایش زمان باقیماندن در محفظه تاریک (TDC) را در تست PAL و همچنین افزایش MDA و کاهش TAC را در مقایسه با گروه کنترل نشان دادند. درمان موش های دیابتیک با الاژیک اسید به شکل معنادار سبب افزایش STLr ، کاهش TDC و افزایش TAC (به وسیله هر دو دوز EA) و کاهش MDA (به وسیله دوز50  mg/kg EA) شد.
    نتیجه گیری
    یافته ها اثر بهبوددهنده حافظه الاژیک اسید را در حیوانات دیابتی از طریق تضعیف استرس اکسیداتیو نشان دادند.
    کلید واژگان: دیابت, الاژیک اسید, حافظه, استرس اکسیداتیو, استرپتوزوتوسین}
    Safoura Raoufi *, Abdolrahman Sarihi, Alireza Komaki, Siamak Shahidi
    Background and Objective
    Diabetes mellitus is associated with memory impairment. Ellagic acid (EA) is a natural polyphenol with anti-diabetic and neuroprotective effects. The aim of the present study was to investigate the protective effect of ellagic acid on diabetes induced memory impairment and to evaluate the role of its antioxidant effect.
    Materials and Methods
    Male Wistar rats were randomly divided into four groups (n=8): control, diabetic, diabetic receiving 25 mg/kg of EA, and diabetic receiving 50 mg/kg of EA. Diabetes was induced by a single intraperitoneal injection of 60 mg/kg of streptozotocin (STZ). After receiving EA (once a day) by oral gavage for four weeks, passive avoidance learning (PAL) test was used to evaluate memory. Finally, oxidative stress related factors including malondialdehyde (MDA) and total antioxidant capacity (TAC) were evaluated in the hippocampal tissue separated from the animal brains under deep anesthesia.
    Results
    Diabetic animals showed marked reductions in step-through latency (STLr) and elevation in time spent in the dark compartment (TDC)  in the retention trial and elevation of MDA level and diminution of TAC compared to controls significantly. Treatment of diabetic rats with EA markedly increased STLr, decreased TDC and enhanced TAC (by both EA doses) and reduced MDA (at a dose of 50 mg/kg of EA).
    Conclusion
    The results displayed learning and memory improving effect of EA in diabetic rats via attenuating oxidative stress.
    Keywords: Diabetes mellitus, Ellagic acid, Memory, Oxidative stress, Streptozotocin}
  • Saeed Mehrzadi, Mohammad Amin Mombeini, Iman Fatemi, Heibatullah Kalantari, Mojtaba Kalantar, Mehdi Goudarzi*
    Introduction

    Acrylamide (ACR) is a toxic substance that has renal toxicity. We aim to investigate the therapeutic activity of ellagic acid (EA) on renal injury induced by ACR in Wistar rats.

    Methods

    Thirty-five male Wistar rats were assigned into 5 groups: the control group (5ml/kg normal saline), the ACR group (20mg/kg ACR), the ACR+EA10 group (ACR and 10mg/kg EA), the ACR+EA30 group (ACR and 30mg/kg EA) and the EA30 group (30mg/kg EA). ACR and EA were daily administered by gavage for 30 days. Renal function was assessed by measuring the sera levels of creatinine (Cr) and blood urea nitrogen (BUN). Renal oxidative and inflammatory markers including malondialdehyde (MDA), nitric oxide (NO), protein carbonyl (PC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). hematoxylinand eosin staining was employed to assess pathological alternations of the kidney.

    Results

    EA (more potentially 30mg/kg) administration alleviated the ACR-induced alterations in Cr and BUN levels. Moreover, EA treatment reduced the elevated levels of MDA, NO and PC as well as TNF-α and IL-1β content in renal tissue. Furthermore, reduced activity of SOD and CAT as well as GSH content in the kidney was increased by EA treatment. EA attenuated the ACR- induced pathological alterations in kidney.

    Conclusion

    These findings suggested that EA could mitigate ACR-induced kidney injury due to its potent antioxidant and anti-inflammatory effects.

    Keywords: Acrylamide, Oxidative stress, Inflammation, Nephrotoxicity, Ellagic acid}
  • Alireza Sarkaki, Khojasteh Hoseinynejad *, Maryam Khombi Shooshtari, Mohammad Rashno
    Objective (s)

    The goal of the current experiment was to define the efficacy and underlying molecular mechanisms of Ellagic acid (EA) on acute kidney injury (AKI) induced impairment in cognitive and synaptic plasticity in rats. 

    Materials and Methods

    Administration of 8 ml/kg glycerol (intramuscular) was used to establish the AKI model. Injured animals were treated by EA (25, 50, and 100 mg/kg, daily, gavage) for 14 consecutive days. To approve the renal injuries and the effects of EA on AKI, creatinine values in serum and urea nitrogen (BUN) values in blood were measured. Cognitive performance was investigated using the Morris water maze test. In vivo long-term potentiation (LTP) was recorded from the hippocampus. Then, the level of IL-10β and TNF-α levels were measured using ELISA kits. The integrity index of the Blood-brain barrier (BBB) was assessed by extravasation of Evans blue dye into the brain.

    Results

    Glycerol injection increased blood urea nitrogen (BUN) and serum creatinine (Scr) levels significantly in the AKI group, and EA treatment resulted in a significant reduction in BUN levels in all concentration groups. Also, a significant reduction in the cerebral EBD concentrations was demonstrated in EA treatment rats. Moreover, the indexes of brain electrophysiology, spatial learning, and memory were improved in the EA administrated group compared with the AKI rats. 

    Conclusion

    The current experiment demonstrated the efficacy of EA in hippocampal complication and cognitive dysfunction secondary to AKI via alleviating the inflammation.

    Keywords: AKI, Ellagic acid, Memory, Rat, Synaptic plasticity}
  • Siamak Shahidi, Alireza Komaki, Safoura Raoufi*, Iraj Salehi, Mohammad Zarei, Mohamadreza Mahdian
    Introduction

    Hyperalgesia is among the current complications of diabetes mellitus; oxidative stress and inflammation were influential in its development. As an herbal component, Ellagic Acid (EA) has some biological activities, including antioxidant and anti-inflammatory effects. This study was designed to evaluate the possible beneficial effect of EA on hypernociception in Streptozotocin (STZ)-induced hyperglycemic rats.

    Methods

    Forty-eight male Wistar rats were divided into the control (receiving vehicle), hyperglycemic, EA (25 mg/kg)-treated control, EA (50 mg/kg)-treated control, EA (25 mg/kg)-treated hyperglycemic, and EA (50 mg/kg)-treated hyperglycemic groups. Hyperglycemia was induced by a single Intraperitoneal (IP) injection of STZ (60 mg/Kg). EA was administered daily by oral gavage for four weeks. The nociceptive response was assessed using Tail-Flick (TF) and Hot-Plate (HP) tests. Also, oxidative stress markers, including Malondialdehyde (MDA), Total Oxidant Status (TOS), and Total Antioxidant Capacity (TAC) in the serum, were evaluated.

    Results

    Hyperglycemic animals were found with significant changes, including a reduction in TF and HP latencies, an elevation in serum MDA level and TOS, and a decrease in serum TAC compared with controls. The treatment of hyperglycemic rats with EA facilitated the reduction of TF latency at the dose of 25 mg/kg and HP latency at 50 mg/kg. Furthermore, EA significantly increased TAC and decreased MDA level at a 50 mg/kg dose and reduced TOS at both doses in the serum of hyperglycemic animals. No significant alterations were found in the parameters studied in EA-treated normal rats.

    Conclusion

    These results displayed the antinociceptive effect of EA in hyperglycemic rats via attenuating oxidative stress. Therefore, EA appears to be a promising agent for managing. Hyperglycemic hypernociception.

    Keywords: Diabetes mellitus, Ellagic acid, Hyperalgesia, Rat, Oxidative stress}
  • مهناز قدیمی یاری، فرشاد فروغی، سیما هاشمی پور، محدرضا رشیدی نوش آبادی، محمدحسین احمدی، بهمن احدی نژاد، حسین خادم حقیقیان*

    هدف:

     اثرات مفید پلی فنول ها در کمک به بهبود وضعیت گلایسمی در بیماران مبتلا به دیابت نوع دو در مطالعات علمی گزارش شده است. این مطالعه باهدف بررسی تاثیر مکمل خوراکی الاژیک اسید (EA) بر شاخص گلایسمی و مقاومت انسولینی در افراد دیابتی نوع دو انجام شد.

    مواد و روش ها

    در این کارآزمایی بالینی تصادفی دو سوکورکنترل شده با دارونما، 44 فرد دیابتی انتخاب شدند. بیماران به طور تصادفی در گروه مداخله (22 نفر) و دارونما (22 نفر) قرارگرفته و به ترتیب کپسول حاوی 180 میلی گرم EA در روز یا دارونما را به مدت 8 هفته دریافت کردند. در ابتدا و انتهای مطالعه اطلاعات دموگرافیک، شاخص های تن سنجی، دریافت مواد غذایی و میزان فعالیت بدنی، فاکتورهای بیوشیمیایی قند خون ناشتا و دوساعته، سطح انسولین پلاسما، درصد هموگلوبین گلیکوزیله (HbA1c) و مقاومت انسولینی (IR) اندازه گیری شد.

    یافته ها

    در ابتدا و انتهای مطالعه به لحاظ فاکتورهای تن سنجی، دریافت مواد غذایی و میزان فعالیت بدنی در دو گروه تفاوت معنی داری وجود نداشت . در انتهای مطالعه، دریافت EA در گروه مداخله باعث کاهش معنی داری در میانگین قند خون ناشتا و دوساعته، سطح انسولین پلاسما، درصد HbA1c و میزان IR در مقایسه با گروه دارونما گردید (05/0>P).

    نتیجه گیری

    مکمل EA می تواند به عنوان یک مکمل آنتی اکسیدانی با منشا غذایی در بیماران مبتلا به دیابت نوع 2 از طریق بهبود عوارض جانبی مزمن مفید باشد. علت این امر شاید مربوط به قدرت آنتی اکسیدانی این پلی فنول باشد.

    کلید واژگان: الاژیک اسید, شاخص گلایسمی, مقاومت به انسولین, دیابت شیرین نوع دو}
    Mahnaz Ghadimi Yari, Farshad Foroughi, Sima Hashemipour, Mohamadreza Rashidi Nooshabadi, MohammadHossein Ahmadi, Bahman Ahadi Nezhad, Hossein Khadem Haghighian*
    Introduction

    The beneficial effects of polyphenols to improve glycemic status in patients with type 2 diabetes have been reported in scientific studies. The aim of this study was to investigate the effect of oral ellagic acid (EA) supplement on glycemic index and insulin resistance in type 2 diabetic patients.

    Materials and Methods

    In this double blind randomized clinical trial, 44 diabetic patients were selected, and were randomly assigned to the intervention group (22 subjects) and placebo (22 subjects) and received a capsule containing 180 mg of EA per day or placebo for 8 weeks, respectively. At the beginning and end of the study, demographic information, anthropometric indices, food intake and physical activity, biochemical factors of fasting and two-hour blood sugar, plasma insulin level, glycosylated hemoglobin percentage (HbA1c) and insulin resistance (IR) were measured.

    Results

    At the beginning and end of the study, there was no significant difference between the two groups in terms of anthropometric indices, food intake and physical activity (P>0.05). At the end of the study, receiving EA in the intervention group significantly reduced fasting and two-hour blood sugar means, plasma insulin levels, HbA1c percentage, and IR levels compared with placebo group (P<0.05).

    Conclusion

    EA supplementation can be helpful as a dietary antioxidant supplement in patients with type 2 diabetes by improving chronic side effects. This may be due to the antioxidant power of this polyphenol.

    Keywords: Ellagic Acid, Glycemic Index, Insulin Resistance, Type 2 Diabetes Mellitus}
  • Meharban Asanaliyar, Pratibha Nadig*, Nagakumar Bharatam
    Introduction

    Syzygium cumini (L.) has been known to be used for diabetes treatment in traditional Indian and Chinese medicine. The present study focuses on the evaluation for glucose uptake and insulin release in vitro and characterization of phytoconstituents of the hydro-ethanolic extract of Syzygium cumini seed (SCE). Further, this report covers the molecular docking findings of the bioactive constituents on the sulfonylurea receptor 1 (SUR1).

    Methods

    A glucose uptake assay of SCE was used to estimate the glucose uptake from the cell lysates and the cell culture supernatants using insulin as the reference standard. Insulin release activity of SCE from RIN-5F cells was estimated using enzyme-linked immunosorbent assay. The phytoconstituents were isolated by preparative HPLC and characterized by mass spectrometry, nuclear magnetic resonance (NMR) and infrared spectroscopy. The molecular docking of bioactive constituents was carried on repaglinide bound to the SUR1.

    Results

    In the presence of SCE, the glucose uptake through L6 myoblast cells increased by 19.91% at 40 µg/mL in comparison with the vehicle control (P < 0.05). Moreover, SCE showed 2.8-fold enhancement of insulin release at 40 µg/mL as compared to the vehicle controls (P < 0.05). Gallic and ellagic acids were the key phytoconstituents isolated from SCE. Molecular docking studies revealed that both gallic acid and ellagic acid bind to the repaglinide binding pocket of SUR1.

    Conclusion

    SCE increases the release of insulin and enhances glucose uptake in vitro, which may contribute to its in vivo anti-diabetic activity. The presence of ellagic acid and gallic acid in SCE may be the cause for enhanced insulin release observed with SCE following binding to SUR1.

    Keywords: Molecular docking, Spectroscopy, Gallic acid, Ellagic acid, RIN-5F cells, L6 myoblasts}
  • فیروزه اسدی، علی رزمی، فواد قاضی زاده، معصومه شفیعی*
    مقدمه

    الاژیک اسید (الاژیتانین مهم در عصاره انار)، می تواند به عنوان یک ترکیب طبیعی و ایمن برای جلوگیری از هیپرتروفی قلب ناشی از افزایش سطح خونی آنژیوتانسین 2 در بسیاری از شرایط پاتولوژیک جذابیت داشته باشد. آنژیوتانسین 2 قادر است از طریق تحریک مسیرهای انتقال پیام مختلفی از جمله کلسینورین / فاکتور هسته ای سلول های T فعال شده (NFAT) به هیپر تروفی قلب منجر شود.

    هدف

    در مطالعه حاضر فعالیت احتمالی ضد هیپرتروفی الاژیک اسید و نقش مسیر انتقال پیام کلسینورین/ NFAT در این فعالیت در مقابل هیپرتروفی ناشی از آنژیوتانسین 2 بر روی کاردیومیوسیت ها مورد بررسی قرار گرفت.

    روش بررسی

    سلول های میوکارد H9c2 یک ساعت قبل از قرار گرفتن در معرض آنژیوتانسین 2 با غلظت های مختلف االژیک اسید مورد تیمار قرار گرفتند. مارکرهای بیولوژیک هیپرتروفی قلب شامل تغییر اندازه و محتوای پروتئین سلول و بیان پروتئین پپتید ناتریورتیک دهلیزی (ANP) به ترتیب با استفاده از میکروسکوپ نوری، روش برادفورد و وسترن بلات تعیین شدند. همچنین تاثیر الاژیک اسید بر بیان پروتئین کلسینورین و جایگزینی هسته ای NFATc4 ،به ترتیب با روش های وسترن بالت و ایمونوفلورسانس بررسی گردید.

    نتایج

    نتایج نشان داد که پیش تیمار با الاژیک اسید می تواند به طور موثر از پاسخ هیپرتروفی ناشی از آنژیوتانسین 2 که با تغییر در بیومارکرهای مرتبط با هیپرتروفی شامل افزایش سایز و محتوای پروتئین سلول و بیان افزایش یافته ANP همراه بود، جلوگیری کند. بعلاوه باعث مهار افزایش بیان کلسینورین ناشی از آنژیوتانسین 2 و جایگزینی هسته ای NFATc4 گردید.

    نتیجه گیری

    به طور خلاصه، یافته های ما نشان داد که الاژیک اسید می تواند به طور موثری هیپرتروفی سلول های قلبی ناشی از آنژیوتانسین 2 را مهار کند. این اولین گزارشی است که نقش مهار مسیر کلسینورین /NFAT را در این اثر محافظتی نشان می دهد. مطالعات آتی به صورت درون تنی، ضروری است تا توانایی الاژیک اسید را در بهبود هیپرتروفی قلبی و گذار آن به طرف نارسایی قلب روشن کند.

    کلید واژگان: الاژیک اسید, کاردیومیوسیت-هایپرتروفی, آنژیوتانسین 2, کلسینورین, سلول های H9c2}
    Firouzeh Asadi, Ali Razmi, Foad Ghazizadeh, Massoumeh Shafiei*
    Background

    Ellagic acid, a major ellagitannin found in pomegranate extract, might be an attractive natural and safe bioactive compound for prevention of cardiac hypertrophy in many pathological conditions that are associated with elevated circulating angiotensin II (Ang II). Ang II stimulates multiple signal transduction pathways involved in hypertrophy including calcineurin/nuclear factor of activated T cell (NFAT).

    Objective

    The present study aimed to explore the possible anti-hypertrophic activity of ellagic acid against Ang II-induced cardiomyocyte hypertrophy and the role of calcineurin/ NFAT signaling pathway in this action.

    Methods

    H9c2 myocardial cells were treated with different concentrations of ellagic acid one hour before exposure to Ang II. Biological markers of cardiac hypertrophy including changes in cell size and protein content, and atrial natriuretic peptide (ANP) protein expression were assessed using light microscopy, Bradford method and western blotting, respectively. The effects of ellagic acid on the protein expression of calcineurin and nuclear localization of NFATc4 were also investigated using western blotting and immunofluorescence assay, respectively.

    Results

    The results showed that pretreatment with ellagic acid could efficiently prevent Ang II-induced hypertrophic response which was associated with changes in hypertrophy-related biomarkers including increase in cell size and protein content, and ANP overexpression. Moreover, ellagic acid inhibited Ang II-induced calcineurin up-regulation and nuclear localization of NFATc4.

    Conclusion

    In summary, our findings showed that ellagic acid effectively inhibited Ang II-induced cardiomyocyte hypertrophy. This is the first report demonstrating the role of calcineurin/NFAT pathway inhibition in this protective effects. Future in vivo studies are required to elucidate if ellagic acid could ameliorate cardiac hypertrophy and its transition to heart failure.

    Keywords: Ellagic acid, Cardiomyocyte-hypertrophy, Angiotensin II, Calcineurin, H9c2 cells}
  • زهرا میرزایی، علی باستانی، علی اکبر حاجی آقا محمدی، محمدرضا رشیدی نوش آبادی، بهمن احدی نژاد، حسین خادم حقیقیان*
    سابقه و هدف

    سندرم روده تحریک پذیر (IBS) نوعی اختلال در عملکرد روده است. استرس اکسیداتیو نقش قابل توجهی در این بیماری دارد. با توجه به اثرات آنتی اکسیدانی الاژیک اسید(EA)، این مطالعه با هدف بررسی تاثیر مکمل یاری الاژیک اسید بر کیفیت زندگی در بیماری IBS طراحی شد.

    مواد و روش ها

     این مطالعه کارآزمایی بالینی دوسوکور در دانشگاه علوم پزشکی قزوین در سال 1398 انجام شد و در آن 44 بیمار واجد شرایط با روش تقسیم تصادفی ساده به دو گروه تقسیم و به مدت 8 هفته روزانه یک کپسول mg180 EA (گروه مداخله) و یک کپسول mg180 حاوی آرد گندم (گروه پلاسبو) دریافت کردند. در ابتدا و انتهای مطالعه، پرسشنامه های دموگرافیک، فعالیت بدنی، یادآمد خوراک 24 ساعته تکمیل گردید. فاکتورهای آشفتگی، پاسخ اجتماعی، نگرانی های سلامتی، تصویر بدنی، ارتباطات، روابط جنسی، ممنوعیت غذایی و اختلال فعالیت روزانه توسط پرسشنامه کیفیت زندگی ویژه بیماران  IBS(IBS-QOL-34) تکمیل شد. یافته ها با نرم افزار V20 SPSS Statistics تجزیه و تحلیل شدند.

    یافته ها:

     در ابتدا و انتهای مطالعه به لحاظ فاکتورهای تن سنجی، تفکیک جنسیتی (52 درصد مرد، 48 درصد زن)، میانگین سنی (مداخله: 93/4 ± 55/36 و داونما: 84/5 ± 29/35)سال، دریافت مواد غذایی و فعالیت بدنی دو گروه تفاوت معنی داری نداشتند (05/0>p). در انتهای مطالعه، مصرف EA، باعث کاهش معنی داری در میانگین امتیاز کلی IBS-QOL نسبت به ابتدا شده و کیفیت زندگی افزایش معنی داری داشت(05/0>P). تغییر معنی داری درکیفیت زندگی درگروه پلاسبو مشاهده نشد (05/0>p).

    استنتاج

    مصرف پلی فنول های غذایی مانندEA، احتمالا از طریق کاهش استرس اکسیداتیو، باعث بهبود عملکرد روده و کیفیت زندگی در بیماری IBS می شود. شماره ثبت کارآزمایی بالینی : 11N20141025019669IRCT

    کلید واژگان: الاژیک اسید, کیفیت زندگی, سندرم روده تحریک پذیر, کارآزمایی بالینی}
    Zahra Mirzaie, Ali Bastani, AliAkbar Haji Aghamohammadi, Mohamadreza Rashidi Nooshabadi, Bahman Ahadi Nezhad, Hossein Khadem Haghighian*
    Background and purpose

    Irritable Bowel Syndrome (IBS) is a type of intestinal dysfunction. Oxidative stress plays a significant pathological role in this disease. Ellagic acid (EA) as a dietary polyphenol is known to have antioxidant effects. This study was designed to investigate the effect of ellagic acid supplementation on quality of life in patients with IBS.

    Materials and methods

    A randomized double blind placebo-controlled clinical trial was carried out in 44 patients with IBS in Qazvin University of Medical Sciences, Iran 2019. The participants were randomly allocated to receive either a capsule containing 180 mg EA per day (n=22) or placebo, a capsule containing 180 mg wheat flour, (n=22) for 8 weeks. At the beginning and end of the study, demographic characteristics and frequency of physical activity were recorded, and 24-hour dietary recall index and the Irritable Bowel Syndrome Quality of Life (IBS-QOL-34) questionnaire were completed. Data analysis was performed in SPSS V20.

    Results

    At the beginning and end of the study, there were no significant differences between the two groups in anthropometric indices, food intake, and physical activity (P>0.05). At the end of the study, EA consumption significantly decreased the mean IBS-QOL total score compared to baseline and significantly increased quality of life (P<0.05). The study showed no significant change in the quality of life in the placebo group (P>0.05).

    Conclusion

    According to this study, dietary polyphenols such as ellagic acid improve bowel function, possibly by reducing oxidative stress, thereby improving the quality of life in patients with IBS. (Clinical Trials Registry Number: IRCT20141025019669N11)

    Keywords: ellagic acid, quality of life, irritable bowel syndrome, clinical trial}
  • Sepideh Nejatbakhsh, Mohsen Ilkhanizadeh Qomi, Mehdi Razzaghi Abyaneh, Zahra Jahanshiri*
    Introduction

    Biofilm formation is one of the specific features of Candida albicans that protects it from antifungal agents and the host immune system. Also, Biofilm formation by C. albicans on the mucosal surfaces and medical devices are responsible for causing Candida nosocomial infection. Here, we investigated the effects of ellagic acid on C. albicans growth and biofilm formation regarding the expression of two essential genes that are involved in adhesion and yeast-hypha transition.

    Methods

    The yeasts were treated with serial two-fold concentrations of ellagic acid (3.125-100 µg/ml) for 48 h at 35°C. The weights of the cultured yeasts were measured as an indicator of the fungal growth, and the biofilm formation was assessed by a tetrazolium salt (XTT) reduction assay. The expressions of HWP1 and ALS3 genes were assayed by real-time PCR.

    Results

    Ellagic acid inhibited C. albicans growth 0.68%-82.44%, dose-dependently. The biofilm formation also reduced 2.61%-68.318%. Also, The expressions of HWP1 and ALS3 genes were notably suppressed by ellagic acid at different concentrations.

    Conclusion

    Our results showed that ellagic acid is a potential candidate to eliminate C. albicans-generated biofilm by suppressing the expression of the involved genes.

    Keywords: Ellagic acid, Candida albicans, Biofilm, Gene}
  • Khadijeh Hassonizadeh Falahieh, Alireza Sarkaki *, Mohammadamin Edalatmanesh, Mohammad Kazem Gharib Naseri, Yaghoob Farbood
    Objective(s)
    Cerebral ischemia/reperfusion (I/R) causes brain inflammation that ultimately causes long time brain function disturbances. We aimed to evaluate the effect of ellagic acid (EA) on anxiety, depression, locomotion behaviors, blood-brain barrier (BBB) permeability, brain edema, and inflammation in male rats with cerebral I/R.
    Materials and Methods
    Sixty male Wistar rats (250-300 g) divided into 6 groups randomly with 10 in each: 1) Sham+Veh; rats submitted to the surgery without any I/R and received vehicle (10% DMSO in normal saline 5 ml/kg, gavages). 2) I/R+Veh; 3-5) I/R+EA; I/R rats received 50, 75 and 100 EA mg/kg, by gavages 3 times daily for one week. The cerebral I/R injury was induced by clamping the bilateral common carotid arteries for 20 minutes followed by reperfusion. Behaviors were tested one week after treatment, and brain tissue cytokines were measured by special ELISA kits.
    Results
    Cerebral I/R disrupted BBB function (P<0.001), increased brain water content (P<0.01), anxiety-like (P<0.001), depression-like (P<0.001) behaviors and cytokines in the brain tissue (P<0.001), while decreased locomotion and exploratory behaviors significantly (P
    Conclusion
    The results suggest that EA could be a potential therapeutic agent against cerebral I/R, possibly through its intertwined anti-inflammatory effects. Further research is required to investigate the involved mechanisms in details.
    Keywords: Anxiety-like behavior, BBB permeability, Brain edema, Cerebral ischemia, reperfusion, Cytokines, Depression-like behavior, Ellagic acid, Exploratory behaviors}
  • Jeannett Alejandra Izquierdo Vega, Eduardo Osiris Madrigal Santillán, Jorge Teodoro Chavez Pagola, Maria Del Carmen Valadez, Manuel Sánchez Gutiérrez *

    Ellagic Acid (EA), is a naturally occurring phenolic found in some fruits and nuts. It has a great variety of biological activities, including properties antioxidant, anti-inflammatory, anti-thrombotic, anti-atherogenic, neuroprotective, hepatoprotective, anti-mutagenic, and anti-carcinogenic agent recently. This review aims to summarize experimental research carried out in vivo and in vitro that evaluated the EA treatment in male reproduction and discussed the mechanisms of action. For this purpose, PubMed and SCOPUS databases were searched to identify publications in this regard.

    Keywords: ellagic acid, polyphenols, Urolithins, Male Reproduction}
  • Ahad Khazaei, Seyyed Mohammad Taghi Mansouri, Amir Siahpoosh, Behnam Ghorbanzadeh*, Saeed Salehi, Mohammad Javad Khodayar
    Background

    Epilepsy is a series of disorders in the central nervous system defined by disruption and abnormality in the electrical activity of the brain. The mechanisms of epilepsy occurrence are not fully determined and the current pharmacological therapeutics have low efficacy and are associated with adverse reactions due to narrow therapeutic indices. Ellagic acid has neuroprotective and antioxidant effects and increases the brain’s GABA levels.

    Objectives

    This study was designed to evaluate the effects of ellagic acid on both maximal electroshock and pentylenetetrazole models of acute seizures in mice.

    Methods

    Ellagic acid was administered at the doses of 25, 50, and 100 mg/kg in the two models of seizures.

    Results

    The results showed that ellagic acid was effective at the lowest dose in the maximal electroshock-induced seizure in mice and the duration of hind limb tonic extension (HLTE) was significantly shorter in this group than in the untreated convulsive group. In the pentylenetetrazole convulsion model, ellagic acid significantly increased the latency to convulsion and Straub tail response. The latencies with ellagic acid were longer in groups treated with ellagic acid 25 mg/kg than with ellagic acid 50 and 100 mg/kg.

    Conclusions

    In conclusion, it seems that ellagic acid has anticonvulsant effects in electroshock and pentylenetetrazole models of convulsion but its effects are attenuated or eliminated at higher doses.

    Keywords: Ellagic Acid, Pentylenetetrazole, Maximal Electroshock, Seizure, Mice}
  • نیما سندگل*، پریسا مالکی
    زمینه و هدف
    الایژیک اسید (EA) یک ترکیب آنتی اکسیدان طبیعی با ساختار فنلی است. در این مطالعه تاثیرات حفاظتی آن بر جمعیت و فعالیت سلول‫های گلیال در مدل حیوانی ام اس در شرایط استرس اکسیداتیو مورد بررسی قرار گرفت. مواد و روش ‫ها: موش‫های C57BL/6 بالغ نر 8 تا 9 هفته ای تهیه و در شرایط استاندارد نگهداری شدند. جهت ایجاد مدل، حیوانات به مدت شش هفته غذای حاوی 2/0 درصد کوپریزون (Cup) را مصرف نمودند. حیوانات به هشت گروه شامل کنترل، کنترل دریافت کننده سه دوز EA (20، 40 و 80 میلی گرم برکیلوگرم) ، Cup و Cup دریافت کننده سه دوز EA تقسیم شدند. در انتها بافت مغز حیوانات توسط روش های مولکولی شامل ایمونوهیستوشیمی (IHC) ، وسترن بلات (WB) و ریل تایم پی سی ار (q-PCR) جهت تجزیه و تحلیل مارکرهای اختصاصی سلول های گلیال مورد استفاده قرار گرفت.
    یافته ها
    آنالیز IHC و WB نشان داد که تنها غلظت بالای EA قادر به کاهش بیان پروتئین های GFAP (شاخص آستروسیت‫های فعال) ، Mac-3 (شاخص میکروگلیال های فعال) ، افزایش بیان پروتئین‫ Olig-2 (شاخص الیگودندروسیت های پیش ساز) و در نهایت کاهش معنادار نسبت پروتئین APC (شاخص الیگودندروسیت های بالغ) به Olig-2 نسبت به گروه Cup می باشد. تجریه و تحلیل q-PCR نیز نشان داد تغییرات بیان mRNA این شاخص ها نیز با تغییرات پروتئین های آن ها همسان بوده و از این رو نتایج قبلی تایید گردید.
    نتیجه گیری
    مصرف (80 میلی گرم بر کیلوگرم) EA به طور موثر فعالیت آستروسیت ها و میکروگلیال ها را کاهش داده و محیط را جهت مهاجرت سلول های پیش ساز الیگودندروسیتی به ناحیه عارضه و تبدیل فرآیندهای تخریبی به مکانیسم های ترمیمی مساعد می نماید.
    کلید واژگان: الایژیک اسید, ایمنوهیستوشیمی, کوپریزون, مالتیپل اسکلروزیس}
    Nima Sanadgol*, Parisa Maleki
    Background and Aim
    Ellagic acid (EA) is a natural antioxidant with phenolic structure. In this study, we evaluate the effects of EA consumption on population and activation of neuroglia cells in the animal model of MS under oxidative stress.
    Materials and Methods
    Mature male mice with age of between 8 to 9 weeks were kept in the standard conditions. For model induction, animals received powder normal diet containing 0.2% Cuprizone (Cup) for six weeks. Mice were divided into eight groups containing control, control receiving three doses of EA (20, 40 and 80 mg/kg), Cup and Cup receiving three doses of EA. Finally, specific glial cell markers in the animal brain tissues were analyzed by molecular methods such as immunohistochemistry (IHC), western blotting (WB) and Real Time-PCR (RT-PCR). Findings: IHC and WB analysis have shown that only high concentration of EA is able to reduce protein expression of GFAP (activated astrocytes marker), Mac-3 (activated microglial marker), increase protein expression of Olig-2 (oligodendrocytes precursor marker) and ultimately significant reduction on APC (mature oligodendrocytes marker)/Olig-2 ratio in comparison with Cup group. In addition, RT-PCR evaluation indicated that changes in the mRNA expression of target markers were consistent with observed changes in their protein expression and therefore, IHC and WB results were confirmed.
    Conclusion
    Consumption of 80 mg/kg of EA effectively decreased activation of astrocytes and microglial and so appropriates environment for migration of oligodendrocyte precursor cells to the lesion area and shifting from damage course into the repair progressions.
    Keywords: Cuprizone, Ellagic acid, Immunohistochemistry, Multiple Sclerosis (MS)}
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