Electronic Theses and Dissertation

Cempaka kuning (Magnolia champaca L.) merupakan salah satu tanaman puspa daerah Provinsi Aceh yang diketahui memiliki aktivitas antiinflamasi, antioksidan, antibakteri, dan antidiabetes. Selain itu, ekstrak tanaman ini telah dilaporkan mampu mempercepat penyembuhan luka pada mencit diabetes yang diinduksi streptozotosin. Meskipun demikian, mekanisme yang mendasari perannya dalam penyembuhan luka diabetic foot ulcer (DFU) masih belum banyak dikaji. Penelitian ini bertujuan menganalisis aktivitas ekstrak metanol daun cempaka kuning yang berkaitan dengan pengendalian inflamasi pada DFU melalui pendekatan in silico dan in vitro. Analisis in silico meliputi penapisan kelayakan senyawa (ADME-Tox), network pharmacology, dan molecular docking. Aktivitas in vitro dievaluasi menggunakan uji penghambatan proteinase dengan metode inhibisi tripsin. Hasil analisis menunjukkan bahwa 16 senyawa aktif memenuhi kriteria sifat fisikokimia, farmakokinetik, dan toksisitas. Analisis network pharmacology mengidentifikasi 11 senyawa yang berinteraksi dengan Matrix Metalloproteinase-9 (MMP-9) melalui jalur pensinyalan Tumor Necrosis Factor (TNF). Analisis molecular docking menunjukkan senyawa aspidospermidin-17-ol, 1-acetyl-19,21-epoxy-15,16-dimethoxy- memiliki afinitas pengikatan terbaik terhadap MMP-9 dengan energi pengikatan −7,7 kcal/mol mendekati ligan kontrol (−8,5 kcal/mol), diikuti cedran-diol, 8S,13- (−7,00 kcal/mol) dan caryophyllene oxide (−6,6 kcal/mol). Cedran-diol, 8S,13- juga menunjukkan kemiripan interaksi residu tertinggi terhadap ligan kontrol (68,8%). Uji penghambatan proteinase menunjukkan persen inhibisi tertinggi sebesar 60,08% pada konsentrasi 1000 µg/mL dengan nilai IC₅₀ sebesar 676,53 ± 53,29 µg/mL. Hasil penelitian menunjukkan bahwa ekstrak metanol daun cempaka kuning memiliki aktivitas penghambatan proteinase serta mengandung senyawa yang berinteraksi dengan MMP-9, sehingga layak untuk diteliti lebih lanjut sebagai sumber senyawa alami dalam pengembangan terapi pendukung DFU.

Yellow champaca (Magnolia champaca L.) is one of the flowering plant species native to Aceh Province, Indonesia, known to possess anti-inflammatory, antioxidant, antibacterial, and antidiabetic activities. Furthermore, extracts of this plant have been reported to accelerate wound healing in streptozotocin-induced diabetic mice. Nevertheless, the underlying mechanism of its role in diabetic foot ulcer (DFU) wound healing remains poorly investigated. This study aimed to analyze the activity of methanol extract of yellow champaca leaves in relation to inflammation control in DFU through in silico and in vitro approaches. In silico analyses included ADME-Tox screening, network pharmacology, and molecular docking, whereas in vitro activity was evaluated using a trypsin inhibition assay. The analysis results showed that 16 active compounds fulfilled the physicochemical, pharmacokinetic, and toxicity criteria. Network pharmacology analysis identified 11 compounds interacting with Matrix Metalloproteinase-9 (MMP-9) through the Tumor Necrosis Factor (TNF) signaling pathway. Molecular docking analysis revealed that Aspidospermidine-17-ol, 1-acetyl-19,21-epoxy-15,16-dimethoxy- exhibited the best binding affinity to MMP-9, with a binding energy of −7.7 kcal/mol, close to that of the control ligand (−8.5 kcal/mol), followed by Cedrane-diol, 8S,13- (−7.00 kcal/mol) and Caryophyllene oxide (−6.6 kcal/mol). Cedrane-diol, 8S,13- also showed the highest residue interaction similarity to the control ligand (68.8%). The proteinase inhibition assay showed the highest inhibition percentage of 60.08% at a concentration of 1000 µg/mL, with an IC₅₀ value of 676.53 ± 53.29 µg/mL. These findings demonstrate that M. champaca methanolic leaf extract exhibits antiproteinase activity and contains bioactive compounds that interact with MMP-9, supporting further investigation for DFU management.