Potensi Senyawa Ekstrak Air Daun Pepaya (Carica papaya L.) dan Daun Pulai (Alstonia scholaris L.) sebagai Inhibitor HMG-KoA Reduktase secara In Silico
Abstract
Ekstrak tunggal air daun pepaya dan pulai diketahui memiliki aktivitas inhibisi HMG-KoA reduktase (in vitro) yang secara in vivo mampu menurunkan kolesterol darah. Kombinasi kedua ekstrak memberi efek sinergis setara lovastatin, tetapi belum diketahui senyawa aktif serta interaksi yang terjadi dengan enzim tersebut. Penelitian bertujuan mengidentifikasi senyawa aktif pada kedua ekstrak tunggal tersebut menggunakan LC-MS/MS, serta prediksi potensi sebagai inhibitor HMG-KoA reduktase melalui studi in silico. Ekstraksi dilakukan menggunakan metode dekokta, ekstrak kemudian dianalisis menggunakan LC-MS/MS, dan diprediksi potensinya sebagai inhibitor HMG-KoA reduktase melalui studi in silico. Terdeteksi masing-masing 28 senyawa aktif pada kedua ekstrak tunggal. Prediksi toksisitas, bioavailabilitas, dan penambatan molekuler menghasilkan 2 senyawa daun pepaya dan 6 senyawa daun pulai potensial. Simpulan penelitian ini adalah senyawa terbaik daun pepaya (2,4-diaminoptiridine glyoxal) dan daun pulai (xenocoumacin 1) serta senyawa potensial lain memiliki interaksi dengan residu katalitik HMG-KoA reduktase pada Ser684, Asp690, Lys691, dan Lys692. Water extract of papaya and pulai leaves is known to have HMG-CoA reductase inhibitory activity (in vitro) which in vivo can lower blood cholesterol. The combination of the two extracts has a synergistic effect equivalent to lovastatin, but the active compound and the interactions that occur with the enzyme are unknown. The aim of the study was to identify the active compounds in both single extracts using LC-MS/MS, as well as to predict their potential as HMG-CoA reductase inhibitors through in silico studies. Extraction was carried out using the decoctal method, the extract was then analyzed using LC-MS/MS, and its potential as an HMG-CoA reductase inhibitor was predicted through in silico studies. Each of the 28 active compounds was detected in both single extracts. Two papaya leaf compounds and 6 pulai leaf compounds were obtained which had the potential to pass the prediction of toxicity, bioavailability, and molecular anchoring. The conclusion of this study was the best compounds from papaya leaves (2,4-diaminoptiridine glyoxal) and pulai leaves (xenocoumacin 1) as well as other potential compounds have interactions with HMG-CoA reductase catalytic residues on Ser684, Asp690, Lys691, and Lys692.
Collections
- UT - Biochemistry [1328]