in silico Investigations on Wound Healing Activity, Toxicity and Pharmacokinetic Profiles of Molecules Obtained from Cotinus Coggygria Plant

Abstract

Cotinus coggygria, also known as the "smoke tree" among the public, positively affects wound healing mechanisms. In this study, it was aimed to determine the toxicity and pharmacokinetic profiles of Gallic acid, Myricetin, Quercetin, Fisetin, Sulfuretin, Butin, and Taxifolin compounds found in the extract obtained from the leaves of the Cotinus coggygria plant by in silico methods. It also aimed to determine which of these molecules are more effective in wound healing. Toxicity predictions of the compounds were performed using in silico modeling techniques. Pharmacokinetic properties were also obtained by utilizing structure-activity relationships. In addition, the wound-healing potentials of each compound were determined by molecular docking analyses. The study results showed that gallic acid, butine, and taxifolin molecules had the highest LD50 values (lowest toxicity) among the studied compounds, with approximately 2000 mg/kg. The study results also revealed that the wound-healing effects of the plant were primarily due to butine, sulfuretin, and fisetin molecules with energy values of -6.12 kcal/mol, -5.58 kcal/mol, and -5.50 kcal/mol, respectively, from their interactions with the relevant pathway, TGF-β protein. The toxicity and wound-healing effects of molecules found in the extract obtained from the leaves of the Cotinus coggygria plant were determined, thus providing useful preliminary information for future studies and medical research with these molecules.

Keywords

• Cotinus coggygria
• Wound-healing
• in silico investigations
• Pharmacokinetic Profile and Toxicity

Cotinus Coggygria Bitkisinden Elde Edilen Moleküllerin Yara İyileştirme Aktivitesi, Toksisitesi ve Farmakokinetik Profilleri Üzerine in silico Araştırmalar

Öz

Halk arasında "duman ağacı" olarak da bilinen Cotinus coggygria bitkisinin, yara iyileşme mekanizmaları üzerine olumlu etkileri bulunmaktadır. Bu çalışmada, C. coggygria bitkisinin yapraklarından elde edilen ekstrakt içerisinde bulunan Gallik asit, Mirisetin, Kuersetin, Fisetin, Sülfüretin, Butin ve Taksifolin bileşiklerinin toksisite ve farmakokinetik profillerinin in silico yöntemlerle belirlenmesi amaçlanmıştır. Ayrıca bu moleküllerden hangisinin yara iyileşme mekanizmaları üzerinde daha etkili olduğunun belirlenmesi de hedeflenmiştir. Bileşiklerin toksisite tahminleri, hayvan deneylerine hızlı ve ucuz bir alternatif olan in silico modelleme teknikleri ile gerçekleştirilmiştir. Farmakokinetik özellikler de yapı-aktivite ilişkilerinden yararlanılarak elde edilmiştir. Ayrıca, her bileşiğin yara iyileştirme potansiyelleri, moleküler yerleştirme analizleri ile belirlenmiştir. Çalışma sonuçları, gallik asit, butin ve taksifolin moleküllerinin incelenen bileşikler arasında yaklaşık 2000 mg/kg ile en yüksek LD50 değerlerine (en düşük toksisite) sahip olduğunu göstermiştir. Çalışma sonuçları, bitkinin yara iyileştirici etkilerinin çoğunlukla, -6,12 kcal/mol, -5,58 kcal/mol ve -5,50 kcal/mol etkileşim enerji değerlerine sahip butin, sülfüretin ve fisetin moleküllerinin, ilgili yolak TGF-β proteini ile etkileşimlerinden kaynaklandığını ortaya koymaktadır.

Anahtar Kelimeler

• Cotinus coggygria
• Yara iyileşmesi
• in silico araştırmalar
• Farmakokinetik Profil ve Toksisite

Kaynakça

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