MOLECULAR DOCKING TERPINEN-4-OL SEBAGAI ANTIINFLAMASI PADA ATEROSKLEROSIS SECARA IN SILICO
| Main Authors: | Susanti, N. M. P., Laksmiani, N. P. L., Noviyanti, N. K. M., Arianti, K. M., Duantara, I K. |
|---|---|
| Format: | Article info application/pdf eJournal |
| Bahasa: | eng |
| Terbitan: |
Program Studi Kimia, FMIPA, Universitas Udayana (Program of Study in Chemistry, Faculty of Mathematics and Natural Sciences, Udayana University), Bali, Indonesia
, 2019
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| Online Access: |
https://ojs.unud.ac.id/index.php/jchem/article/view/51722 https://ojs.unud.ac.id/index.php/jchem/article/view/51722/30677 |
Daftar Isi:
- Atherosclerosis is a chronic inflammatory disease that begins with endothelial dysfunction, it caused fat accumulation and plaque growth in the inner arteries walls. Endothelial dysfunction will activate the Mitogen Activated Protein Kinase (MAPK) pathway involving ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins, as well as the Nuclear Factor Kappa B (NF-kB) pathway involving IKK proteins. Terpinen-4-ol is constituent found in the bangle rhizome. The purpose of this study were to determine the affinity and mechanisms of terpinen-4-ol against ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins as anti-inflammatory in atherosclerosis performed using molecular docking method. The study was conducted exploratively with several steps such as preparation and optimization of terpinen-4-ol structure, preparation of 3D ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins, validation method of molecular docking, and docking terpinen-4-ol in these proteins. The docking result are assessed from the binding energy and hydrogen bonds formed between terpinen-4-ol and proteins. The smaller value of binding energy terpinen-4-ol with target proteins showed the complex that form more stable. The result showed that terpinen-4-ol and has activity in inhibiting the inflammatory process because it is able to disturb ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins with respective bond energy values -5,12; -5,24; -5,08; -5,88; and -4,99 Kcal/mol. The molecular mechanism in inhibiting the activity of ERK1, ERK2, JNK1, JNK2, and p38MAPK proteins is through the formation of hydrogen bonds in these proteins. These results show that terpinen-4-ol have the potential to inhibit inflammatory process and the formation of atherosclerotic plaque can be obstructed. Keywords : atherosclerosis, terpinen-4-ol, molecular docking, in silico
- Aterosklerosis merupakan penyakit inflamasi kronis yang diawali dengan disfungsi endotel sehingga terjadi penumpukan lemak dan pertumbuhan plak pada dinding dalam arteri. Disfungsi endotel akan mengaktifkan jalur Mitogen Activated Protein Kinase (MAPK) yang melibatkan protein ERK1, ERK2, JNK1, JNK2, dan p38MAPK, serta jalur Nuclear Factor Kappa B (NF-?B) yang melibatkan protein IKK. Terpinen-4-ol merupakan konstituen yang terdapat di dalam rimpang bangle (Zingiber cassumunar Roxb.) yang diketahui memiliki aktivitas antiinflamasi. Tujuan dari penelitian ini adalah untuk mengetahui afinitas dan mekanisme terpinen-4-ol terhadap protein ERK1, ERK2, JNK1, JNK2, dan p38MAPK sebagai antiinflamasi pada aterosklerosis yang dilakukan menggunakan metode molecular docking. Penelitian dilakukan secara eksploratif dengan tahapan preparasi dan optimasi struktur 3D terpinen-4-ol, preparasi struktur 3D protein ERK1, ERK2, JNK1, JNK2, dan p38MAPK, validasi metode molecular docking, serta docking terpinen-4-ol pada protein-protein tersebut. Hasil docking dinilai dari energi ikatan dan ikatan hidrogen yang terbentuk antara terpinen-4-ol dengan protein. Semakin rendah nilai energi ikatan antara terpinen-4-ol dengan protein target, maka kompleks yang terbentuk semakin stabil. Hasil penelitian menunjukkan bahwa terpinen-4-ol memiliki aktivitas dalam menghambat proses inflamasi karena mampu menghambat protein ERK1, ERK2, JNK1, JNK2, dan p38MAPK dengan nilai energi ikatan masing-masing -5,12; -5,24; -5,08; -5,88; dan -4,99 Kkal/mol. Mekanisme molekuler dalam menghambat aktivitas protein ERK1, ERK2, JNK1, JNK2, dan p38MAPK melalui pembentukan ikatan hidrogen pada protein-protein tersebut. Hasil tersebut memperlihatkan bahwa terpinen-4-ol berpotensi menghambat proses inflamasi sehingga pembentukan plak aterokslerosis dapat terhambat. Kata kunci : aterosklerosis, terpinen-4-ol, molecular docking, in silico