استكشاف الأهداف المضادة للالتهابات في الفلافونويدات من خلال الالتحام الجزيئي المتكامل وعلم الأدوية الشبكي
DOI:
https://doi.org/10.35516/jjps.v18i1.2713الكلمات المفتاحية:
مضاد للالتهابات، حمض الفيروليك، الهسبيريدين، الالتحام الجزيئي، علم الأدوية الشبكي، كيرسيتين، روتينالملخص
الالتهاب هو استجابة فسيولوجية معقدة مرتبطة بالعديد من الأمراض. أظهرت الفلافونويدات، وهي فئة من المركبات الطبيعية المنتشرة على نطاق واسع في النباتات، خصائص مضادة للالتهابات واعدة. ومع ذلك، تظل آليات عملها الشاملة وأهدافها الجزيئية المحتملة غير قابلة للتعريف. في الدراسة الحالية، استخدمنا نهج علم الأدوية الشبكي جنبًا إلى جنب مع الالتحام الجزيئي للتحقيق في التأثيرات المضادة للالتهابات لبعض الفلافونويدات. في البداية، قمنا بجمع وتنظيم قاعدة بيانات شاملة مثل معلمات وأهداف ADMET من ADME السويسرية وADMET 2.O وتوقع الهدف السويسري. ثم قمنا ببناء شبكة تفاعل بروتين-بروتين لتحديد البروتينات الرئيسية المشاركة في الالتهاب باستخدام قاعدة بيانات السلسلة. بعد ذلك، قمنا بدمج مجموعة بيانات الفلافونويد مع شبكة البروتين لتحديد تفاعلات الفلافونويد-البروتين المحتملة باستخدام Cytosacpe vina. تم إجراء تحليل إثراء GO وKEGG بمساعدة قاعدة بيانات David. تم إنجاز الالتحام الجزيئي من خلال Autodock Vina، وتقييم تقارب ارتباط الفلافونويدات المحددة تجاه البروتينات المستهدفة المحددة. قدم تحليل الالتحام رؤى حول التفاعلات المحددة بين الفلافونويدات والبروتينات المستهدفة، موضحًا الآليات المحتملة الكامنة وراء تأثيراتها المضادة للالتهابات. تعمل المكونات النشطة بيولوجيًا حمض الفيروليك، والكيرسيتين، والروتين، والهسبيريدين على تعديل العديد من العمليات الجزيئية والخلوية ثم تمارس تأثيرات مضادة للالتهابات. من التحليل، شاركت الأهداف الرئيسية في مرض التهاب الأمعاء، ومسار إشارات IL 17، ومسار إشارات TNF، ومسار إشارات بوساطة السيتوكين، والتهاب المفاصل الروماتويدي، والليبوبوليساكاريد وما إلى ذلك. كشفت دراسات الالتحام الجزيئي الإضافية أيضًا أن تقارب الارتباط للفلافونويدات المحددة كان أعلى من تقارب الديكلوفيناك.
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