Collective In Silico Studies Reveal Bioactive Compounds from Sea Grapes (Caulerpa lentillifera) Target p38 MAPK for Potential Anti Aging Applications

Haiva Kezia, Dr. Sci. apt. Rohmad Yudi Utomo, M.Sc.

2022 | Skripsi | FARMASI

Penuaan kulit merupakan proses alami yang menyebabkan hilangnya

kolagen dan penuaan seluler yang sering diperburuk oleh stres oksidatif. p38

MAPK berpernan penting dalam ekspresi sitokin inflamasi dan degradasi kolagen.

Anggur laut (Caulerpa lentillifera) merupakan sumber senyawa bioaktif yang

menjanjikan sebagai agen anti-aging alami melalui perlindungan seluler dan

kesehatan kulit. Namun, penelitian mengenai pengaruhnya terhadap jalur p38

MAPK masih terbatas. Penelitian ini bertujuan untuk mengeksplorasi apakah

senyawa dari anggur laut dapat berinteraksi dengan p38 MAPK melalui pendekatan

in silico. Dari 275 senyawa yang dikumpulkan, sebanyak 213 senyawa lolos

penyaringan sesuai aturan Lipinski’s Rule of Five. Skrining machine learning dalam

studi ini menggunakan 3 algoritme model yang dimana Random Forest

menunjukkan performa prediksi paling andal (AUC = 0,838) dan menunjukkan

bahwa 69 dari 114 senyawa diprediksi sebagai aktif. Molecular docking terhadap

p38 MAPK mengidentifikasi tiga senyawa terbaik, dengan senyawa 113 (CID

45782854) memperoleh skor docking terbaik sebesar ?8,2303 kkal/mol. Di antara

kandidat terbaik, senyawa 20 menunjukkan profil farmakokinetik in silico yang

relatif lebih baik. Prediksi toksisitas menunjukkan bahwa semua senyawa

diklasifikasikan sebagai sensitasi lemah (1B). Temuan ini mengindikasikan bahwa

anggur laut menunjukkan potensinya sebagai agen anti-aging. Namun, studi

eksperimental lebih lanjut dibutuhkan untuk mengkonfirmasi studi dan

mengevaluasi potensi terapeutiknya secara mendalam.

Skin aging is a natural process that leads to collagen loss and cellular aging,

which is often caused by oxidative stress. One of the main regulatory protein that

plays a role in this process is known as p38 MAPK. This protein contributes to

collagen degradation. Sea grape (Caulerpa lentillifera) is a promising marine

macroalga rich of bioactive molecules as a natural anti-aging agent that is potential

to support cellular protection and skin health. However, there are still limited

studies regarding the inhibition of the p38 MAPK pathway involving these

bioactive compounds. This study aims to explore whether bioactive compounds

from sea grapes can interact with p38 MAPK through an in silico approach. From

275 bioactive compounds that were compiled into one dataset, 213 compounds

were successfully passed the Lipinski’s Rule of Five. Machine learning process

used three models to identify the activity prediction of bioactive compounds

towards the target protein, with Random Forest demonstrated the most reliable

performance (AUC = 0.838) and showed 69 out of 213 compounds were predicted

active. Molecular docking towards p38 MAPK identified compound 113 (CID

45782854) obtained the highest docking score of ?8.2303 kcal/mol. Among the top

candidates, Compound 20 demonstrated a favorable in silico pharmacokinetic

profile. Toxicity prediction showed that all of the three compounds were classified

as weak sensitizers (1B). These findings suggest that sea grape has a potential as a

natural anti-aging agent. However, further experimental studies are needed to

confirm and evaluate its therapeutic potential.

Kata Kunci : Anti-Aging, Caulerpa lentillifera, Cellular Senescence, In Silico, Molecular Docking, Oxidative Stress, p38 MAPK