Electronic Theses and Dissertation

Kawasan manifestasi geotermal Seulawah Agam di Provinsi Aceh merupakan ekosistem ekstrem yang kaya akan keanekaragaman tumbuhan. Kondisi lingkungan khas seperti suhu tinggi, kandungan mineral yang unik, dan aktivitas vulkanik diyakini mendorong biosintesis metabolit sekunder yang berbeda dari tumbuhan di ekosistem normal. Namun, potensi farmakologi molekuler dari tumbuhan di wilayah ini, khususnya dalam konteks anti-inflamasi, masih belum banyak dieksplorasi secara ilmiah. Penelitian ini bertujuan untuk menyaring kandidat senyawa anti-inflamasi dari tumbuhan yang tumbuh di tiga titik manifestasi geotermal Seulawah Agam: Ie-Seu’um, Ie-Jue, dan Ie-Brouk. Pendekatan yang digunakan bersifat komprehensif dan multidisipliner, meliputi identifikasi spesies tumbuhan obat lokal, evaluasi aktivitas antioksidan menggunakan 2,2-diphenyl-1-picrylhydrazyl-hydrate (DPPH), dan uji toksisitas awal (brine shrimp lethality assay atau BSLA). Senyawa bioaktif kemudian dianalisis menggunakan metode Gas Chromatography-Mass Spectrometry (GC- MS) dan Liquid Chromatography-High Resolution Mass Spectrometry (LC- HRMS) untuk mendapatkan profil metabolit yang menyeluruh. Seleksi kandidat tumbuhan dilakukan dengan metode Analytical Hierarchy Process (AHP), dan senyawa terpilih dianalisis lebih lanjut menggunakan pendekatanNetwork Pharmacology untuk memprediksi target protein terkait inflamasi seperti TNF-α, IL-6, JAK1, dan NF-κB. Simulasi molecular docking digunakan untuk mengevaluasi afinitas dan stabilitas interaksi antara senyawa dan protein target. Hasil penelitian mengungkapkan 80 senyawa bioaktif, di antaranya quercetin, luteolin, catechin, caffeic acid, ursolic acid, dan proximadiol. Senyawa-senyawa ini menunjukkan potensi tinggi dalam memodulasi jalur inflamasi seperti NF-κB, JAK-STAT, MAPK, dan TNF signaling pathways. Uji lanjutan pada Lantana camara secara in vitro menunjukkan aktivitas anti-inflamasi yang sebanding dengan aspirin, sementara Chromolaena odorata memperlihatkan profil senyawa anti-inflamasi yang bervariasi antar lokasi. Penelitian ini menegaskan bahwa tumbuhan dari lingkungan geotermal Seulawah Agam merupakan sumber potensial kandidat obat alami untuk terapi penyakit inflamasi kronis. Strategi integratif yang digunakan dapat menjadi model eksplorasi tumbuhan obat dari ekosistem ekstrem lainnya.

The geothermal manifestation areas of Seulawah Agam, located in Aceh Province, Indonesia, represent a unique extreme ecosystem characterized by high temperatures, rich mineral content, and volcanic activity. These environmental factors are believed to influence the biosynthesis of secondary metabolites in plants, potentially leading to the production of novel bioactive compounds. However, the molecular pharmacological potential of medicinal plants in this region, particularly for anti-inflammatory purposes, remains underexplored. This study aimed to screen potential anti-inflammatory compounds from plants growing in three geothermal manifestation sites: Ie-Seu’um, Ie-Jue, and Ie-Brouk. A multidisciplinary and integrative approach was employed, including the identification of local medicinal plant species, evaluation of antioxidant activity using the DPPH method, and initial toxicity screening through the Brine Shrimp Lethality Assay (BSLA). Bioactive compounds were profiled using Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography–High Resolution Mass Spectrometry (LC-HRMS) to obtain a comprehensive metabolite profile. Plant selection was refined using the Analytical Hierarchy Process (AHP), and selected compounds were further investigated through aNetwork Pharmacology approach to predict interactions with inflammation-related protein targets, such as TNF-α, IL-6, JAK1, and NF-κB. Molecular docking simulations were conducted to assess the binding affinity and stability between these compounds and the respective inflammatory targets. The study identified 80 bioactive compounds, including quercetin, luteolin, catechin, caffeic acid, ursolic acid, and proximadiol. These compounds demonstrated strong potential to modulate inflammatory pathways, particularly NF-κB, JAK-STAT, MAPK, and TNF signaling. Further in vitro assays using Lantana camara extracts showed anti- inflammatory activity comparable to aspirin, while Chromolaena odorata exhibited varied anti-inflammatory potential across different locations. This research highlights the untapped potential of geothermal medicinal plants in Seulawah Agam as a natural source of anti-inflammatory drug candidates. The integrative methodology applied in this study offers a systematic and evidence- based strategy for herbal drug discovery, which can be extended to other extreme ecosystems worldwide.