Astrocyte-Targeted Transporter-Utilizing Derivatives of Ferulic Acid Can Have Multifunctional Effects Ameliorating Inflammation and Oxidative Stress in the Brain
المؤلفون المشاركون
Huttunen, Kristiina M.
Montaser, Ahmed
Huttunen, Johanna
Ibrahim, Sherihan Abdelhamid
المصدر
Oxidative Medicine and Cellular Longevity
العدد
المجلد 2019، العدد 2019 (31 ديسمبر/كانون الأول 2019)، ص ص. 1-13، 13ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2019-11-13
دولة النشر
مصر
عدد الصفحات
13
التخصصات الرئيسية
الملخص EN
Ferulic acid (FA) is a natural phenolic antioxidant, which can exert also several other beneficial effects to combat neuroinflammation and neurodegenerative diseases, such as Alzheimer’s disease.
One of these properties is the inhibition of several enzymes and factors, such as β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), cyclooxygenases (COXs), lipoxygenases (LOXs), mammalian (or mechanistic) target for rapamycin (mTOR), and transcription factor NF-κB.
We have previously synthesized three L-type amino acid transporter 1- (LAT1-) utilizing FA-derivatives with the aim to develop brain-targeted prodrugs of FA.
In the present study, the cellular uptake and bioavailability of these FA-derivatives were evaluated in mouse primary astrocytic cell cultures together with their inhibitory effects towards BACE1, COX/LOX, mTOR, NF-κB, acetylcholinesterase (AChE), and oxidative stress.
According to the results, all three FA-derivatives were taken up 200–600 times more effectively at 10 μM concentration into the astrocytes than FA, with one derivative having a high intracellular bioavailability (Kp,uu), particularly at low concentrations.
Moreover, all of the derivatives were able to inhibit BACE1, COX/LOX, AChE, and oxidative stress measured as decreased cellular lipid peroxidation.
Furthermore, one of the derivatives modified the total mTOR amount.
Therefore, these derivatives have the potential to act as multifunctional compounds preventing β-amyloid accumulation as well as combating inflammation and reducing oxidative stress in the brain.
Thus, this study shows that converting a parent drug into a transporter-utilizing derivative not only may increase its brain and cellular uptake, and bioavailability but can also broaden the spectrum of pharmacological effects elicited by the derivative.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Montaser, Ahmed& Huttunen, Johanna& Ibrahim, Sherihan Abdelhamid& Huttunen, Kristiina M.. 2019. Astrocyte-Targeted Transporter-Utilizing Derivatives of Ferulic Acid Can Have Multifunctional Effects Ameliorating Inflammation and Oxidative Stress in the Brain. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1203271
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Montaser, Ahmed…[et al.]. Astrocyte-Targeted Transporter-Utilizing Derivatives of Ferulic Acid Can Have Multifunctional Effects Ameliorating Inflammation and Oxidative Stress in the Brain. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-13.
https://search.emarefa.net/detail/BIM-1203271
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Montaser, Ahmed& Huttunen, Johanna& Ibrahim, Sherihan Abdelhamid& Huttunen, Kristiina M.. Astrocyte-Targeted Transporter-Utilizing Derivatives of Ferulic Acid Can Have Multifunctional Effects Ameliorating Inflammation and Oxidative Stress in the Brain. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-13.
https://search.emarefa.net/detail/BIM-1203271
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1203271
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
تقوم هذه الخدمة بالتحقق من التشابه أو الانتحال في الأبحاث والمقالات العلمية والأطروحات الجامعية والكتب والأبحاث باللغة العربية، وتحديد درجة التشابه أو أصالة الأعمال البحثية وحماية ملكيتها الفكرية. تعرف اكثر